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1.  Sagittal Abdominal Diameter as a New Predictor for Incident Diabetes 
Diabetes Care  2013;36(2):283-288.
Obesity, particularly visceral adiposity, is a major risk factor for type 2 diabetes. The commonly used obesity indicators, BMI, waist girth, and waist-to-hip ratio (WHR), have limited ability to measure the visceral adipose tissue. Sagittal abdominal diameter (SAD) has been shown to predict the amount of visceral fat. So far no study has been published on its ability to predict diabetes occurrence.
We assessed and compared the prediction of the four obesity indicators for diabetes incidence in a prospective study based on 5,168 participants from the nationally representative Health 2000 study.
During a mean follow-up lasting 8.1 years, 222 incident diabetes cases occurred. In multivariate models adjusted for lifestyle factors, BMI, waist girth, WHR, and SAD were significant predictors of diabetes incidence. The relative risks (95% CI) between high and low levels were 15.0 (6.94–32.6), 11.4 (5.39–23.8), 12.5 (6.47–24.2), and 14.7 (6.89–31.2), respectively. Pairwise interaction analysis showed that the co-occurrence of high BMI and high SAD was associated with the highest diabetes incidence, with a relative risk of 37.0 (11.2–122). After adjustment for waist girth and the components of the metabolic syndrome, the relative risk was 9.88 (2.81–34.7). The corresponding population-attributable fraction estimate was 84% (49–95).
The combination of SAD and BMI measurements yields a new predictor of diabetes incidence.
PMCID: PMC3554316  PMID: 22961578
2.  Scrutiny of the CHRNA5-CHRNA3-CHRNB4 smoking behavior locus reveals a novel association with alcohol use in a Finnish population based study 
The CHRNA5-CHRNA3-CHRNB4 gene cluster on chromosome 15q25.1 encoding the cholinergic nicotinic receptor subunits is robustly associated with smoking behavior and nicotine dependence. Only a few studies to date have examined the locus with alcohol related traits and found evidence of association with alcohol abuse and dependence. Our main goal was to examine the role of three intensively studied single nucleotide polymorphisms, rs16969968, rs578776 and rs588765, tagging three distinct loci, in alcohol use. Our sample was drawn from two independent Finnish population-based surveys, the National FINRISK Study and the Health 2000 (Health Examination) Survey. The combined sample included a total of 32,592 adult Finns (54% women) of whom 8,356 were assessed for cigarettes per day (CPD). Data on alcohol use were available for 31,812 individuals. We detected a novel association between rs588765 and alcohol use defined as abstainers and low-frequency drinkers versus drinkers (OR=1.15, p=0.00007). Additionally, we provide precise estimates of strength of the association between the three loci and smoking quantity in a very large population based sample. As a conclusion, our results provide further evidence for the nicotine-specific role of rs16969968 (locus 1). Further, our data suggest that the effect of rs588765 (locus 3) may be specific to alcohol use as the effect is seen also in never smokers.
PMCID: PMC3709115  PMID: 23875064
Nicotinic acetylcholine receptors; 15q25.1; alcohol use; smoking behavior; public health; population-based sample; genetic association
3.  Self-administered questionnaire was a reliable measure for coffee consumption 
The objective of this study was to assess the agreement and the repeatability of two methods measuring habitual coffee consumption, and to examine their homogeneity by socioeconomic and lifestyle factors.
Data on coffee consumption were collected for 4,254 subjects from a health questionnaire (HQ) and from a 1-year dietary history interview (DHI) used as the reference method during the Finnish Mobile Clinic Health Examination Survey conducted in 1973–1976. Short-term repeatability of the methods was assessed based on 286 and 93 subjects who repeated the HQ and the DHI after an interval of 4–8 months, respectively. The strength of agreement between the two methods and between the repeated measurements was estimated using the intraclass correlation coefficient (ICC).
The ICC was 0.86 for the agreement between the HQ and the DHI, and 0.77 and 0.85 for the repeatability of the HQ and the DHI, respectively. No statistically significant systematic differences in the mean intake values were found between the two methods or repeated measurements. The agreement and repeatability showed only minor differences in subgroups of background variables, with somewhat higher ICC values among subjects with a healthier lifestyle and higher education.
The study showed that the health questionnaire was a useful tool for measuring habitual coffee consumption for purposes of epidemiological research, due to its high reliability and homogeneity.
PMCID: PMC3655324  PMID: 20671374
agreement; coffee; lifestyle; repeatability; socioeconomic factors
5.  Vertebral fracture and cause-specific mortality: a prospective population study of 3,210 men and 3,730 women with 30 years of follow-up 
European Spine Journal  2011;20(12):2181-2186.
Vertebral fractures predict mortality, but little is known about their associations with the causes of death. We studied vertebral fractures for prediction of cause-specific mortality.
Material and methods
A nationally representative sample of 3,210 men and 3,730 women participated Mini-Finland health survey in 1978–1980. Vertebral fractures at the Th1–Th12 levels were identified from chest radiographs at baseline. Cox’s proportional hazard model was used to estimate the strength of association between vertebral fracture and mortality.
The relative risk (95% confidence interval) of death from natural causes was 1.49 (0.89–2.48) in men and 0.89 (0.60–1.31) in women with vertebral fractures (adjusted for age, body mass index, serum 25-hydroxyvitamin D, educational level, smoking, alcohol intake, physical activity and self-rated general health). Among women the adjusted relative risk of an injury death was 8.51 (3.48–20.77), whereas none of the men with vertebral fracture died due to an injury.
The patterns of mortality predicted by fracture in the thoracic spine differ between men and women.
PMCID: PMC3229726  PMID: 21611851
Vertebral fracture; Osteoporosis; Hip fracture; Cause-specific mortality
6.  Development and Validation of a Job Exposure Matrix for Physical Risk Factors in Low Back Pain 
PLoS ONE  2012;7(11):e48680.
The aim was to construct and validate a gender-specific job exposure matrix (JEM) for physical exposures to be used in epidemiological studies of low back pain (LBP).
Materials and Methods
We utilized two large Finnish population surveys, one to construct the JEM and another to test matrix validity. The exposure axis of the matrix included exposures relevant to LBP (heavy physical work, heavy lifting, awkward trunk posture and whole body vibration) and exposures that increase the biomechanical load on the low back (arm elevation) or those that in combination with other known risk factors could be related to LBP (kneeling or squatting). Job titles with similar work tasks and exposures were grouped. Exposure information was based on face-to-face interviews. Validity of the matrix was explored by comparing the JEM (group-based) binary measures with individual-based measures. The predictive validity of the matrix against LBP was evaluated by comparing the associations of the group-based (JEM) exposures with those of individual-based exposures.
The matrix includes 348 job titles, representing 81% of all Finnish job titles in the early 2000s. The specificity of the constructed matrix was good, especially in women. The validity measured with kappa-statistic ranged from good to poor, being fair for most exposures. In men, all group-based (JEM) exposures were statistically significantly associated with one-month prevalence of LBP. In women, four out of six group-based exposures showed an association with LBP.
The gender-specific JEM for physical exposures showed relatively high specificity without compromising sensitivity. The matrix can therefore be considered as a valid instrument for exposure assessment in large-scale epidemiological studies, when more precise but more labour-intensive methods are not feasible. Although the matrix was based on Finnish data we foresee that it could be applicable, with some modifications, in other countries with a similar level of technology.
PMCID: PMC3495969  PMID: 23152793
7.  Leisure time physical activity in a 22-year follow-up among Finnish adults 
The aim of this study was to explore long-term predictors of leisure time physical activity in the general population.
This study comprised 718 men and women who participated in the national Mini-Finland Health Survey from 1978–1980 and were re-examined in 2001. Participants were aged 30–80 at baseline. Measurements included interviews, health examinations, and self-administered questionnaires, with information on socioeconomic position, occupational and leisure time physical activity, physical fitness, body mass index, smoking, alcohol consumption, and physical functional capacity. Analyses included persons who were working and had no limitations in functional capacity at baseline.
The strongest predictor of being physically active at the follow-up was participation in physical activity at baseline, with an OR 13.82 (95%CI 5.50-34.70) for 3 or more types of regular activity, OR 2.33 (95%CI 1.22-4.47) for 1–2 types of regular activity, and OR 3.26 (95%CI 2.07-5.15) for irregular activity, as compared to no activity. Other determinants for being physically active were moving upwards in occupational status, a high level of baseline occupational physical activity and remaining healthy weight during the follow-up.
To prevent physical inactivity among older adults, it is important to promote physical activity already in young adulthood and in middle age and to emphasize the importance of participating in many types of physical activity.
PMCID: PMC3502146  PMID: 23031224
Exercise; Health behavior; Occupation; Prospective studies; Socioeconomic position
8.  Associations of Nicotine Intake Measures With CHRN Genes in Finnish Smokers 
Nicotine & Tobacco Research  2011;13(8):686-690.
Genetic effects contribute to individual differences in smoking behavior. Persistence to smoke despite known harmful health effects is mostly driven by nicotine addiction. As the physiological effects of nicotine are mediated by nicotinic acetylcholine receptors (nAChRs), we aimed at examining whether single nucleotide polymorphisms (SNPs) residing in nAChR subunit (CHRN) genes, other than CHRNA3/CHRNA5/CHRNB4 gene cluster previously showing association in our sample, are associated with smoking quantity or serum cotinine levels.
The study sample consisted of 485 Finnish adult daily smokers (age 30–75 years, 59% men) assessed for the number of cigarettes smoked per day (CPD) and serum cotinine level. We first studied SNPs residing on selected nAChR subunit genes (CHRNA2, CHRNA4, CHRNA6/CHRNB3, CHRNA7, CHRNA9, CHRNA10, CHRNB2, CHRNG/CHRND) genotyped within a genome-wide association study for single SNP and multiple SNP associations by ordinal regression. Next, we explored individual haplotype associations using sliding window technique.
At one of the 8 loci studied, CHRNG/CHRND (chr2), single SNP (rs1190452), multiple SNP, and 2-SNP haplotype analyses (SNPs rs4973539–rs1190452) all showed statistically significant association with cotinine level. The median cotinine levels varied between the 2-SNP haplotypes from 220 ng/ml (AA haplotype) to 249 ng/ml (AG haplotype). We did not observe significant associations with CPD.
These results provide further evidence that the γ−δ nAChR subunit gene region is associated with cotinine levels but not with the number of CPD, illustrating the usefulness of biomarkers in genetic analyses.
PMCID: PMC3150688  PMID: 21498873
9.  Evidence of Inbreeding Depression on Human Height 
McQuillan, Ruth | Eklund, Niina | Pirastu, Nicola | Kuningas, Maris | McEvoy, Brian P. | Esko, Tõnu | Corre, Tanguy | Davies, Gail | Kaakinen, Marika | Lyytikäinen, Leo-Pekka | Kristiansson, Kati | Havulinna, Aki S. | Gögele, Martin | Vitart, Veronique | Tenesa, Albert | Aulchenko, Yurii | Hayward, Caroline | Johansson, Åsa | Boban, Mladen | Ulivi, Sheila | Robino, Antonietta | Boraska, Vesna | Igl, Wilmar | Wild, Sarah H. | Zgaga, Lina | Amin, Najaf | Theodoratou, Evropi | Polašek, Ozren | Girotto, Giorgia | Lopez, Lorna M. | Sala, Cinzia | Lahti, Jari | Laatikainen, Tiina | Prokopenko, Inga | Kals, Mart | Viikari, Jorma | Yang, Jian | Pouta, Anneli | Estrada, Karol | Hofman, Albert | Freimer, Nelson | Martin, Nicholas G. | Kähönen, Mika | Milani, Lili | Heliövaara, Markku | Vartiainen, Erkki | Räikkönen, Katri | Masciullo, Corrado | Starr, John M. | Hicks, Andrew A. | Esposito, Laura | Kolčić, Ivana | Farrington, Susan M. | Oostra, Ben | Zemunik, Tatijana | Campbell, Harry | Kirin, Mirna | Pehlic, Marina | Faletra, Flavio | Porteous, David | Pistis, Giorgio | Widén, Elisabeth | Salomaa, Veikko | Koskinen, Seppo | Fischer, Krista | Lehtimäki, Terho | Heath, Andrew | McCarthy, Mark I. | Rivadeneira, Fernando | Montgomery, Grant W. | Tiemeier, Henning | Hartikainen, Anna-Liisa | Madden, Pamela A. F. | d'Adamo, Pio | Hastie, Nicholas D. | Gyllensten, Ulf | Wright, Alan F. | van Duijn, Cornelia M. | Dunlop, Malcolm | Rudan, Igor | Gasparini, Paolo | Pramstaller, Peter P. | Deary, Ian J. | Toniolo, Daniela | Eriksson, Johan G. | Jula, Antti | Raitakari, Olli T. | Metspalu, Andres | Perola, Markus | Järvelin, Marjo-Riitta | Uitterlinden, André | Visscher, Peter M. | Wilson, James F. | Gibson, Greg
PLoS Genetics  2012;8(7):e1002655.
Stature is a classical and highly heritable complex trait, with 80%–90% of variation explained by genetic factors. In recent years, genome-wide association studies (GWAS) have successfully identified many common additive variants influencing human height; however, little attention has been given to the potential role of recessive genetic effects. Here, we investigated genome-wide recessive effects by an analysis of inbreeding depression on adult height in over 35,000 people from 21 different population samples. We found a highly significant inverse association between height and genome-wide homozygosity, equivalent to a height reduction of up to 3 cm in the offspring of first cousins compared with the offspring of unrelated individuals, an effect which remained after controlling for the effects of socio-economic status, an important confounder (χ2 = 83.89, df = 1; p = 5.2×10−20). There was, however, a high degree of heterogeneity among populations: whereas the direction of the effect was consistent across most population samples, the effect size differed significantly among populations. It is likely that this reflects true biological heterogeneity: whether or not an effect can be observed will depend on both the variance in homozygosity in the population and the chance inheritance of individual recessive genotypes. These results predict that multiple, rare, recessive variants influence human height. Although this exploratory work focuses on height alone, the methodology developed is generally applicable to heritable quantitative traits (QT), paving the way for an investigation into inbreeding effects, and therefore genetic architecture, on a range of QT of biomedical importance.
Author Summary
Studies investigating the extent to which genetics influences human characteristics such as height have concentrated mainly on common variants of genes, where having one or two copies of a given variant influences the trait or risk of disease. This study explores whether a different type of genetic variant might also be important. We investigate the role of recessive genetic variants, where two identical copies of a variant are required to have an effect. By measuring genome-wide homozygosity—the phenomenon of inheriting two identical copies at a given point of the genome—in 35,000 individuals from 21 European populations, and by comparing this to individual height, we found that the more homozygous the genome, the shorter the individual. The offspring of first cousins (who have increased homozygosity) were predicted to be up to 3 cm shorter on average than the offspring of unrelated parents. Height is influenced by the combined effect of many recessive variants dispersed across the genome. This may also be true for other human characteristics and diseases, opening up a new way to understand how genetic variation influences our health.
PMCID: PMC3400549  PMID: 22829771
10.  Long-term results of surgery for lumbar spinal stenosis: a randomised controlled trial 
European Spine Journal  2011;20(7):1174-1181.
We randomised a total of 94 patients with long-standing moderate lumbar spinal stenosis (LSS) into a surgical group and a non-operative group, with 50 and 44 patients, respectively. The operative treatment comprised undercutting laminectomy of stenotic segments, augmented with transpedicular-instrumented fusion in suspected lumbar instability. The primary outcome was the Oswestry disability index (ODI), and the other main outcomes included assessments of leg and back pain and self-reported walking ability, all based on questionnaire data from 85 patients at the 6-year follow-up. At the 6-year follow-up, the mean difference in ODI in favour of surgery was 9.5 (95% confidence interval 0.9–18.1, P-value for global difference 0.006), whereas the intensity of leg or back pain did not differ between the two treatment groups any longer. Walking ability did not differ between the treatment groups at any time. Decompressive surgery of LSS provided modest but consistent improvement in functional ability, surpassing that obtained after non-operative measures.
PMCID: PMC3175822  PMID: 21240530
Spinal stenosis; Surgical treatment; Non-operative treatment; Randomised controlled trial
11.  Genome-wide association and large scale follow-up identifies 16 new loci influencing lung function 
Artigas, María Soler | Loth, Daan W | Wain, Louise V | Gharib, Sina A | Obeidat, Ma’en | Tang, Wenbo | Zhai, Guangju | Zhao, Jing Hua | Smith, Albert Vernon | Huffman, Jennifer E | Albrecht, Eva | Jackson, Catherine M | Evans, David M | Cadby, Gemma | Fornage, Myriam | Manichaikul, Ani | Lopez, Lorna M | Johnson, Toby | Aldrich, Melinda C | Aspelund, Thor | Barroso, Inês | Campbell, Harry | Cassano, Patricia A | Couper, David J | Eiriksdottir, Gudny | Franceschini, Nora | Garcia, Melissa | Gieger, Christian | Gislason, Gauti Kjartan | Grkovic, Ivica | Hammond, Christopher J | Hancock, Dana B | Harris, Tamara B | Ramasamy, Adaikalavan | Heckbert, Susan R | Heliövaara, Markku | Homuth, Georg | Hysi, Pirro G | James, Alan L | Jankovic, Stipan | Joubert, Bonnie R | Karrasch, Stefan | Klopp, Norman | Koch, Beate | Kritchevsky, Stephen B | Launer, Lenore J | Liu, Yongmei | Loehr, Laura R | Lohman, Kurt | Loos, Ruth JF | Lumley, Thomas | Al Balushi, Khalid A | Ang, Wei Q | Barr, R Graham | Beilby, John | Blakey, John D | Boban, Mladen | Boraska, Vesna | Brisman, Jonas | Britton, John R | Brusselle, Guy G | Cooper, Cyrus | Curjuric, Ivan | Dahgam, Santosh | Deary, Ian J | Ebrahim, Shah | Eijgelsheim, Mark | Francks, Clyde | Gaysina, Darya | Granell, Raquel | Gu, Xiangjun | Hankinson, John L | Hardy, Rebecca | Harris, Sarah E | Henderson, John | Henry, Amanda | Hingorani, Aroon D | Hofman, Albert | Holt, Patrick G | Hui, Jennie | Hunter, Michael L | Imboden, Medea | Jameson, Karen A | Kerr, Shona M | Kolcic, Ivana | Kronenberg, Florian | Liu, Jason Z | Marchini, Jonathan | McKeever, Tricia | Morris, Andrew D | Olin, Anna-Carin | Porteous, David J | Postma, Dirkje S | Rich, Stephen S | Ring, Susan M | Rivadeneira, Fernando | Rochat, Thierry | Sayer, Avan Aihie | Sayers, Ian | Sly, Peter D | Smith, George Davey | Sood, Akshay | Starr, John M | Uitterlinden, André G | Vonk, Judith M | Wannamethee, S Goya | Whincup, Peter H | Wijmenga, Cisca | Williams, O Dale | Wong, Andrew | Mangino, Massimo | Marciante, Kristin D | McArdle, Wendy L | Meibohm, Bernd | Morrison, Alanna C | North, Kari E | Omenaas, Ernst | Palmer, Lyle J | Pietiläinen, Kirsi H | Pin, Isabelle | Polašek, Ozren | Pouta, Anneli | Psaty, Bruce M | Hartikainen, Anna-Liisa | Rantanen, Taina | Ripatti, Samuli | Rotter, Jerome I | Rudan, Igor | Rudnicka, Alicja R | Schulz, Holger | Shin, So-Youn | Spector, Tim D | Surakka, Ida | Vitart, Veronique | Völzke, Henry | Wareham, Nicholas J | Warrington, Nicole M | Wichmann, H-Erich | Wild, Sarah H | Wilk, Jemma B | Wjst, Matthias | Wright, Alan F | Zgaga, Lina | Zemunik, Tatijana | Pennell, Craig E | Nyberg, Fredrik | Kuh, Diana | Holloway, John W | Boezen, H Marike | Lawlor, Debbie A | Morris, Richard W | Probst-Hensch, Nicole | Kaprio, Jaakko | Wilson, James F | Hayward, Caroline | Kähönen, Mika | Heinrich, Joachim | Musk, Arthur W | Jarvis, Deborah L | Gläser, Sven | Järvelin, Marjo-Riitta | Stricker, Bruno H Ch | Elliott, Paul | O’Connor, George T | Strachan, David P | London, Stephanie J | Hall, Ian P | Gudnason, Vilmundur | Tobin, Martin D
Nature Genetics  2011;43(11):1082-1090.
Pulmonary function measures reflect respiratory health and predict mortality, and are used in the diagnosis of chronic obstructive pulmonary disease (COPD). We tested genome-wide association with the forced expiratory volume in 1 second (FEV1) and the ratio of FEV1 to forced vital capacity (FVC) in 48,201 individuals of European ancestry, with follow-up of top associations in up to an additional 46,411 individuals. We identified new regions showing association (combined P<5×10−8) with pulmonary function, in or near MFAP2, TGFB2, HDAC4, RARB, MECOM (EVI1), SPATA9, ARMC2, NCR3, ZKSCAN3, CDC123, C10orf11, LRP1, CCDC38, MMP15, CFDP1, and KCNE2. Identification of these 16 new loci may provide insight into the molecular mechanisms regulating pulmonary function and into molecular targets for future therapy to alleviate reduced lung function.
PMCID: PMC3267376  PMID: 21946350
12.  Effect of Five Genetic Variants Associated with Lung Function on the Risk of Chronic Obstructive Lung Disease, and Their Joint Effects on Lung Function 
Rationale: Genomic loci are associated with FEV1 or the ratio of FEV1 to FVC in population samples, but their association with chronic obstructive pulmonary disease (COPD) has not yet been proven, nor have their combined effects on lung function and COPD been studied.
Objectives: To test association with COPD of variants at five loci (TNS1, GSTCD, HTR4, AGER, and THSD4) and to evaluate joint effects on lung function and COPD of these single-nucleotide polymorphisms (SNPs), and variants at the previously reported locus near HHIP.
Methods: By sampling from 12 population-based studies (n = 31,422), we obtained genotype data on 3,284 COPD case subjects and 17,538 control subjects for sentinel SNPs in TNS1, GSTCD, HTR4, AGER, and THSD4. In 24,648 individuals (including 2,890 COPD case subjects and 13,862 control subjects), we additionally obtained genotypes for rs12504628 near HHIP. Each allele associated with lung function decline at these six SNPs contributed to a risk score. We studied the association of the risk score to lung function and COPD.
Measurements and Main Results: Association with COPD was significant for three loci (TNS1, GSTCD, and HTR4) and the previously reported HHIP locus, and suggestive and directionally consistent for AGER and TSHD4. Compared with the baseline group (7 risk alleles), carrying 10–12 risk alleles was associated with a reduction in FEV1 (β = –72.21 ml, P = 3.90 × 10−4) and FEV1/FVC (β = –1.53%, P = 6.35 × 10−6), and with COPD (odds ratio = 1.63, P = 1.46 × 10−5).
Conclusions: Variants in TNS1, GSTCD, and HTR4 are associated with COPD. Our highest risk score category was associated with a 1.6-fold higher COPD risk than the population average score.
PMCID: PMC3398416  PMID: 21965014
FEV1; FVC; genome-wide association study; modeling risk
13.  Association between Obesity History and Hand Grip Strength in Older Adults—Exploring the Roles of Inflammation and Insulin Resistance as Mediating Factors 
To examine the association between obesity history and hand grip strength, and whether the association is partly explained by subclinical inflammation and insulin resistance.
Data are from 2,021 men and women aged 55 years and older participating in the representative population-based Health 2000 Survey in Finland. Body mass and body height, maximal hand grip strength, C-reactive protein, and insulin resistance based on homeostasis model assessment (HOMA-IR) were measured in a health examination. Recalled weight at 20, 30, 40, and 50 years of age were recorded to obtain a hierarchical classification of obesity history. Obesity was defined as body mass index ≥ 30 kg/m2.
Earlier onset of obesity was associated with lower hand grip strength (p < .001) after controlling for age, sex, education, smoking, alcohol use, physical activity, several chronic diseases, and current body weight. Based on adjusted logistic regression models, the odds (95% confidence interval) for very low relative hand grip strength were 2.76 (1.78–4.28) for currently obese, 5.57 (3.02–10.28) for obese since age of 50 years, 6.53 (2.98–14.30) for obese since age of 40 years, and 10.36 (3.55–30.24) for obese since age of 30 years compared with never obese participants. The associations remained highly significant even after adjusting for current C-reactive protein and HOMA-IR, but these variables had only minor role in explaining the association between obesity history and hand grip strength.
Long-term exposure to obesity is associated with poor hand grip strength later in life. Maintaining healthy body weight throughout the life span may help to maintain adequate muscle strength in old age. Prospective studies with information on prior muscle strength are needed to examine in detail the causal association between obesity history and muscle strength.
PMCID: PMC3041473  PMID: 21310808
Muscle strength; Obesity; Inflammation; Insulin resistance; Aging
14.  Hand-Grip Strength Cut-Points to Screen Older Persons at Risk for Mobility Limitation 
To determine optimal hand-grip strength cut-points for increased likelihood for mobility limitation among older people and to study whether these cut-points differ according to body mass index (BMI).
Design and setting
Cross-sectional analysis of data collected in the Finnish population-based Health 2000 Survey.
Participants and measurements
1 084 men and 1 562 women aged 55 years and older with complete data on anthropometry, hand-grip strength and self-reported mobility. Mobility limitation was defined as difficulties in walking 0.5-km or climbing stairs. Receiver Operating Characteristics analysis was used to estimate hand-grip strength cut-points for increased likelihood for mobility limitation.
The overall hand-grip strength cut-points for increased likelihood for mobility limitation were 37 kg (sensitivity 62% and specificity 76%) for men and 21 kg (67% and 73%) for women. Hand-grip strength by BMI interaction on mobility limitation was significant among men (p = 0.022), while no such interaction was observed among women (p = 0.156). Among men, most optimal cut-offs were 33 kg (73% and 79%) for normal-weight men, 39 kg (67% and 71%) for overweight men and 40 kg (57% and 68%) for obese men. Among women, BMI-specific hand-grip strength cut-off values did not markedly increase accuracy over the overall cut-off value.
Hand-grip strength test is a useful tool to identify persons with increased risk for mobility limitation. Among men, the hand-grip strength cut-points for mobility increased along with BMI, while among women only one hand-grip strength threshold was identified.
PMCID: PMC2946262  PMID: 20863331
muscle strength; functional capacity; mobility; body mass index; ROC analysis
15.  Serum vitamin D and the risk of Parkinson’s disease 
Archives of neurology  2010;67(7):808-811.
Low vitamin D status has been suggested to be related to Parkinson’s disease risk.
To investigate whether serum vitamin D level predicts the risk of Parkinson’s disease.
Design, Setting and Participants
The study was based on the Mini–Finland Health survey, which was conducted in 1978–1980, and followed-up for Parkinson’s disease occurrence through the end of 2007. The study population consisted of 3173 men and women, aged 50–79 years and free from Parkinson’s disease at baseline. During the 29–year follow–up period, 50 incident Parkinson’s disease cases occurred. Serum vitamin D (25(OH)D) was determined from frozen samples, stored at baseline. Estimates of the relationship between serum vitamin D concentration and Parkinson’s disease incidence were calculated using Cox’s model.
Main Outcome Measure
Parkinson’s disease incidence
Individuals with higher serum vitamin D concentrations showed a reduced risk of Parkinson’s disease. The relative risk between the highest and lowest quartiles was 0.33 (95% CI 0.14–0.80) after adjustment for sex, age, marital status, education, alcohol consumption, leisure-time physical activity, smoking, body mass index, and month of blood draw.
The results are consistent with the suggestion that high vitamin D status provides protection against Parkinson’s disease. It cannot, however, be excluded that the finding is due to residual confounding and further studies are thus needed.
PMCID: PMC3091074  PMID: 20625085
16.  Associations of cardiovascular risk factors, carotid intima-media thickness and manifest atherosclerotic vascular disease with carpal tunnel syndrome 
The role of atherosclerosis in carpal tunnel syndrome (CTS) has not previously been addressed in population studies. The aim of this study was to investigate the associations of cardiovascular risk factors, carotid artery intima-media thickness (IMT), and clinical atherosclerotic diseases with CTS.
In this cross sectional study, the target population consisted of subjects aged 30 or over who had participated in the national Finnish Health Survey in 2000-2001. Of the 7977 eligible subjects, 6254 (78.4%) were included in our study. Carotid IMT was measured in a sub-sample of subjects aged 45 to 74 (N = 1353).
Obesity (adjusted odds ratio (OR) 2.4, 95% confidence interval (CI) 1.1-5.4), high LDL cholesterol (OR 3.8, 95% CI 1.6-9.1 for >190 vs. <129 mg/dL), high triglycerides (OR 2.7, 95% CI 1.2-6.1 for >200 vs. <150 mg/dL), hypertension (OR 3.4, 95% CI 1.6-7.4) and cardiac arrhythmia (OR 10.2, 95% CI 2.7-38.4) were associated with CTS in subjects aged 30-44. In the age group of 60 years or over, coronary artery disease (OR 1.9, 95% CI 1.1-3.5), valvular heart disease (OR 2.3, 95% CI 1.0-5.0) and carotid IMT (1.4, 95% CI 0.9-2.1 for each 0.23 mm increase) were associated with CTS. Carotid IMT was associated with CTS only in subjects with hypertension or clinical atherosclerotic vascular disease, or in those who were exposed to physical workload factors.
Our findings suggest an association between CTS and cardiovascular risk factors in young people, and carotid IMT and clinical atherosclerotic vascular disease in older people. CTS may either be a manifestation of atherosclerosis, or both conditions may share similar risk factors.
PMCID: PMC3116486  PMID: 21521493
Atherosclerosis; carotid artery; coronary artery disease; hypertension; obesity; smoking; wrist
17.  Dextrocardia and coronal alignment of thoracic curve: a population study 
European Spine Journal  2009;18(12):1941-1945.
The objective of this study was to evaluate the coronal alignment of the thoracic spine in persons with dextrocardia. Generally, the thoracic spine is slightly curved to the right. It has been suggested that the curve could be triggered by pulsation forces from the descending aorta. Since no population study has focused on the alignment of the thoracic spine in persons with situs inversus, dextrocardia, and right-sided descending aorta, we compared the radiographs of the thoracic spine in persons with dextrocardia to those having normal levocardia. Among 57,440 persons in a health survey, 11 cases of dextrocardia were identified through standard radiological screening. The miniature chest radiographs of eight persons were eligible for the present study. The study was carried out as a nested case–control study. Four individually matched (age, gender, and municipality) controls with levocardia were chosen for each case. Coronal alignment of the thoracic spine was analyzed without knowledge of whether the person had levo- or dextrocardia. A mild convexity to the left was found in all persons with dextrocardia and right-sided descending aorta (mean Cobb angle 6.6° to the left, SD 2.9). Of the 32 normal levocardia persons, 29 displayed a convexity to the right, and the remaining three had a straight spine (mean Cobb angle 5.2° to the right, SD 2.3). The difference (mean 11.8°, SD 3.5) differed significantly from unity (P = 0.00003). In conclusion, it seems that a slight left convexity of the thoracic spine is frequent in dextrocardia. We assume that the effect of the repetitive pulsatile pressure of the descending thoracic aorta, and the mass effect of the heart may cause the direction of the convexity to develop opposite to the side of the aortic arch.
PMCID: PMC2899440  PMID: 19506918
Situs inversus; Dextrocardia; Left thoracic curve; Aorta
18.  Autoantibodies binding to citrullinated telopeptide of type II collagen and to cyclic citrullinated peptides predict synergistically the development of seropositive rheumatoid arthritis 
Annals of the Rheumatic Diseases  2007;66(11):1450-1455.
To find out whether autoantibodies to citrullinated telopeptides of type I and II collagens and to cyclic citrullinated peptides (CCPs) predict the development of rheumatoid arthritis (RA).
A case‐control study (matched for sex, age and municipality) was nested within a Finnish cohort of 19072 adults who had neither arthritis nor a history of it at the baseline examination during 1973–7. 124 subjects developed RA by late 1989, and of these, 89 were positive for rheumatoid factor (RF). Preillness serum specimens were analysed for autoantibodies against arginine (A)‐ or citrulline (C)‐containing synthetic telopeptides using a chemiluminescence method and for anti‐CCPs Mark2 with an enzyme‐linked immunosorbent assay method.
The mean levels of autoantibodies to citrulline‐containing telopeptides and the C/A ratios of type I and II collagens and to CCP were higher in subjects who later developed RF‐positive RA. In the highest tertiles of C/A (I), C/A (II) ratios and anti‐CCPs levels, the relative risk of RF‐positive RA was significantly increased. In the multifactorial model, only anti‐CCPs retained its statistical significance. However, the interaction term of C/A (II) ratio and anti‐CCPs proved to be statistically significant (p = 0.02). The subjects ranked into the highest tertiles of both C/A (II) ratio and anti‐CCPs had an odds ratio of 20.06 (95% confidence interval, 4.37 to 92.06) of developing RF‐positive RA compared with those in the lowest tertiles of these antibodies. None of the autoantibodies predicted RF‐negative RA.
Autoantibodies to citrullinated telopeptides of type I and II collagen and to CCPs exert a synergistic effect on the risk of seropositive RA.
PMCID: PMC2111613  PMID: 17472989
19.  Association of serum cotinine level with a cluster of three nicotinic acetylcholine receptor genes (CHRNA3/CHRNA5/CHRNB4) on chromosome 15 
Human Molecular Genetics  2009;18(20):4007-4012.
A cluster of three nicotinic acetylcholine receptor genes on chromosome 15 (CHRNA5/CHRNA3/CHRNB4) has been shown to be associated with nicotine dependence and smoking quantity. The aim of this study was to clarify whether the variation at this locus regulates nicotine intake among smokers by using the level of a metabolite of nicotine, cotinine, as an outcome. The number of cigarettes smoked per day (CPD) and immune-reactive serum cotinine level were determined in 516 daily smokers (age 30–75 years, 303 males) from the population-based Health2000 study. Association of 21 SNPs from a 100 kb region of chromosome 15 with cotinine and CPD was examined. SNP rs1051730 showed the strongest association to both measures. However, this SNP accounted for nearly a five-fold larger proportion of variance in cotinine levels than in CPD (R2 4.3% versus 0.9%). The effect size of the SNP was 0.30 for cotinine level, whereas it was 0.13 for CPD. Variation at CHRNA5/CHRNA3/CHRNB4 cluster influences nicotine level, measured as cotinine, more strongly than smoking quantity, measured by CPD, and appears thus to be involved in regulation of nicotine levels among smokers.
PMCID: PMC2748889  PMID: 19628476
20.  Self-Administered Questionnaire Is a Reliable Measure of Coffee Consumption 
Journal of Epidemiology  2010;20(5):363-369.
The objective of this study was to assess the agreement and repeatability of 2 methods of measuring habitual coffee consumption, and to examine their homogeneity with respect to socioeconomic and lifestyle factors.
Data on coffee consumption were collected from 4254 subjects by means of a health questionnaire (HQ) and a 1-year dietary history interview (DHI), the latter of which was used as the reference method during the Finnish Mobile Clinic Health Examination Survey conducted in 1973–1976. Short-term repeatability of the methods was assessed using data from 286 and 93 subjects who repeated the HQ and the DHI, respectively, after an interval of 4 to 8 months. The strength of agreement between the 2 methods and between the repeated measurements was estimated using intraclass correlation coefficients (ICCs).
The ICC was 0.86 for the agreement between the HQ and the DHI, and 0.77 and 0.85 for the repeatability of the HQ and the DHI, respectively. There were no statistically significant systematic differences in mean intake values between the 2 methods or between repeated measurements. In subgroup analysis of background variables, there were only minor differences in agreement and repeatability, with somewhat higher ICC values among subjects with a healthier lifestyle and higher education.
The high reliability and homogeneity of the health questionnaire make it a useful tool for measuring habitual coffee consumption for the purposes of epidemiological research.
PMCID: PMC3655324  PMID: 20671374
agreement; coffee; lifestyle; repeatability; socioeconomic factors
21.  Multiple Independent Loci at Chromosome 15q25.1 Affect Smoking Quantity: a Meta-Analysis and Comparison with Lung Cancer and COPD 
PLoS Genetics  2010;6(8):e1001053.
Recently, genetic association findings for nicotine dependence, smoking behavior, and smoking-related diseases converged to implicate the chromosome 15q25.1 region, which includes the CHRNA5-CHRNA3-CHRNB4 cholinergic nicotinic receptor subunit genes. In particular, association with the nonsynonymous CHRNA5 SNP rs16969968 and correlates has been replicated in several independent studies. Extensive genotyping of this region has suggested additional statistically distinct signals for nicotine dependence, tagged by rs578776 and rs588765. One goal of the Consortium for the Genetic Analysis of Smoking Phenotypes (CGASP) is to elucidate the associations among these markers and dichotomous smoking quantity (heavy versus light smoking), lung cancer, and chronic obstructive pulmonary disease (COPD). We performed a meta-analysis across 34 datasets of European-ancestry subjects, including 38,617 smokers who were assessed for cigarettes-per-day, 7,700 lung cancer cases and 5,914 lung-cancer-free controls (all smokers), and 2,614 COPD cases and 3,568 COPD-free controls (all smokers). We demonstrate statistically independent associations of rs16969968 and rs588765 with smoking (mutually adjusted p-values<10−35 and <10−8 respectively). Because the risk alleles at these loci are negatively correlated, their association with smoking is stronger in the joint model than when each SNP is analyzed alone. Rs578776 also demonstrates association with smoking after adjustment for rs16969968 (p<10−6). In models adjusting for cigarettes-per-day, we confirm the association between rs16969968 and lung cancer (p<10−20) and observe a nominally significant association with COPD (p = 0.01); the other loci are not significantly associated with either lung cancer or COPD after adjusting for rs16969968. This study provides strong evidence that multiple statistically distinct loci in this region affect smoking behavior. This study is also the first report of association between rs588765 (and correlates) and smoking that achieves genome-wide significance; these SNPs have previously been associated with mRNA levels of CHRNA5 in brain and lung tissue.
Author Summary
Nicotine binds to cholinergic nicotinic receptors, which are composed of a variety of subunits. Genetic studies for smoking behavior and smoking-related diseases have implicated a genomic region that encodes the alpha5, alpha3, and beta4 subunits. We examined genetic data across this region for over 38,000 smokers, a subset of which had been assessed for lung cancer or chronic obstructive pulmonary disease. We demonstrate strong evidence that there are at least two statistically independent loci in this region that affect risk for heavy smoking. One of these loci represents a change in the protein structure of the alpha5 subunit. This work is also the first to report strong evidence of association between smoking and a group of genetic variants that are of biological interest because of their links to expression of the alpha5 cholinergic nicotinic receptor subunit gene. These advances in understanding the genetic influences on smoking behavior are important because of the profound public health burdens caused by smoking and nicotine addiction.
PMCID: PMC2916847  PMID: 20700436
22.  Lifestyle and metabolic factors in relation to shoulder pain and rotator cuff tendinitis: A population-based study 
Shoulder pain is a common health problem. The purpose of this study was to assess the associations of lifestyle factors, metabolic factors and carotid intima-media thickness with shoulder pain and chronic (> 3 months) rotator cuff tendinitis.
In this cross-sectional study, the target population consisted of subjects aged 30 years or older participating in a national Finnish Health Survey during 2000-2001. Of the 7,977 eligible subjects, 6,237 (78.2%) participated in a structured interview and clinical examination. Chronic rotator cuff tendinitis was diagnosed clinically. Weight-related factors, C-reactive protein and carotid intima-media thickness were measured.
The prevalence of shoulder joint pain during the preceding 30 days was 16% and that of chronic rotator cuff tendinitis 2.8%. Smoking, waist circumference and waist-to-hip ratio were related to an increased prevalence of shoulder pain in both genders. Metabolic syndrome, type 2 diabetes mellitus and carotid intima-media thickness were associated with shoulder pain in men, whereas high level of C-reactive protein was associated with shoulder pain in women. Increased waist circumference and type 1 diabetes mellitus were associated with chronic rotator cuff tendinitis in men.
Our findings showed associations of abdominal obesity, some other metabolic factors and carotid intima-media thickness with shoulder pain. Disturbed glucose metabolism and atherosclerosis may be underlying mechanisms, although not fully supported by the findings of this study. Prospective studies are needed to further investigate the role of lifestyle and metabolic factors in shoulder disorders.
PMCID: PMC3161397  PMID: 20646281
23.  Educational differences in mobility: the contribution of physical workload, obesity, smoking and chronic conditions 
In earlier studies, determinants of socioeconomic gradient in mobility have not been measured comprehensively.
To assess the contribution of chronic morbidity, obesity, smoking and physical workload to inequalities in mobility.
This was a cross‐sectional study on 2572 persons (76% of a nationally representative sample of the Finnish population aged ⩾55 years). Mobility limitations were measured by self‐reports and performance rates.
According to a wide array of self‐reported and test‐based indicators, persons with a lower level of education showed more mobility limitations than those with a higher level. The age‐adjusted ORs for limitations in stair climbing were threefold in the lowest‐educational category compared with the highest one (OR 3.3 in men and 2.9 in women for self‐reported limitations, and 3.5 in men and 2.2 in women for test‐based limitations). When obesity, smoking, work‐related physical loading and clinically diagnosed chronic diseases were simultaneously accounted for, the educational differences in stair‐climbing limitations vanished or were greatly diminished. In women, obesity contributed most to the differences, followed by a history of physically strenuous work, knee and hip osteoarthritis and cardiovascular diseases. In men, diabetes, work‐related physical loading, musculoskeletal diseases, obesity and smoking contributed substantially to the inequalities.
Great educational inequalities exist in various measures of mobility. Common chronic diseases, obesity, smoking and workload appeared to be the main pathways from low education to mobility limitations. General health promotion using methods that also yield good results in the lowest‐educational groups is thus a good strategy to reduce the disparities in mobility.
PMCID: PMC2465686  PMID: 17435206
24.  Fat free mass and obesity in relation to educational level 
BMC Public Health  2009;9:448.
The aim of the study was to describe the body composition of Finnish adults, especially by education, and to investigate whether fat-free mass (FFM) can explain educational gradients relating to body mass index (BMI) and waist-to-hip ratio (WHR).
Data for this cross-sectional study were based on data collected in 2000-2001 for the Health 2000 Survey. Of the nationally representative sample of 8,028 Finnish men and women aged 30 years and older, 6,300 (78.5%) were included in the study. Body composition measurements were carried out in the health examination, where FFM was assessed with eight-polar bioelectrical impedance analysis. Questions on education were included in the health interview.
The mean FFM varied by education in older (≥ 65 y.) men only. In the middle-aged group (30-64 y.), highly educated men were less likely to belong to the lowest quintile of FFM (OR 0.67, 95%CI 0.48-0.93) compared with the least educated subjects. The level of education was inversely associated with the prevalence of high BMI and WHR in middle-aged men. In women, the respective associations were found both in middle-aged women and their older counterparts. Adjustment for FFM slightly strengthened the associations of education with BMI and WHR.
The association between education and FFM is weak. Educational gradients of high BMI and high WHR cannot be explained by FFM.
PMCID: PMC2801678  PMID: 19961589
25.  Regular use of traditional analgesics predicts major coronary events: A cohort study 
Serious concern has arisen about the cardiovascular safety of selective cyclo-oxygenase-2 (COX-2) inhibitors. However, recent studies have shown that the cardiovascular risks of regular use of traditional analgesics also deserve attention. We investigated the use of traditional analgesics for their prediction of major coronary events during 16 years of follow-up.
A population sample of 8000 Finns aged 30 years and over was invited to a comprehensive health examination in 1978–1980; 7217 (90%) complied, and 4824 of these had no diagnosed cardiovascular disease. The participants filled in a questionnaire eliciting information on the use of analgesics. Record linkage to the National Hospital Discharge Register and the mortality register of the Central Statistical Office of Finland identified 266 major coronary events (myocardial infarctions or coronary deaths) by the end of 1994.
The risk of a major coronary event was significantly elevated among those reporting regular use of analgesics at baseline. Compared with nonusers and adjusted for known risk factors for coronary heart disease, the relative risk of an event during the whole follow-up period was 1.51 (95% confidence interval [CI] 1.08–2.10) among regular users of analgesics. The risk was as high as 5.27 (95% CI 2.13–13.11) during the first two years of the follow-up. Thereafter it leveled off.
Based on sales statistics almost all analgesics used in Finland at the end of the 1970’s were nonsteroidal antiinflammatory drugs (NSAIDs). Therefore, the increased risk of major coronary events among regular users of analgesics is likely to be due to traditional NSAIDs.
PMCID: PMC2697508  PMID: 19436602
acute myocardial infarction; coronary heart disease; cohort study; analgesics; pharmacology; risk factors

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