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2.  Life History, Immune Function, and Intestinal Helminths: Trade-Offs Among Immunoglobulin E, C-Reactive Protein, and Growth in an Amazonian Population 
Objectives
Infection with helminths is associated with shifts in host immunity, including increased production of immunoglobulin E (IgE) and reduced inflammation. Given limited energy budgets, these shifts may involve changes in energy allocation toward competing demands. Here we test for potential trade-offs between growth, IgE, and the inflammatory marker C-reactive protein (CRP).
Methods
Dried blood spots and anthropometrics were collected from 162 Shuar forager-horticulturalists from a village in southeastern Ecuador. Enzyme-linked immunosorbent assays (ELISAs) were used to measure IgE and CRP. Relationships among IgE, CRP, and anthropometrics were examined in three groups: children aged 2–7 years (n = 63), children aged 8–15 (n = 61), and adults over age 18 (n = 37).
Results
Geometric mean IgE was 1,196 IU ml−1 while geometric mean CRP was 1.33 mg l−1. In children, IgE and CRP were negatively correlated (r = −0.21, P = 0.02, df = 122). Controlling for fat stores and age, IgE was associated with lower stature in children (t = −2.04, P = 0.04, df = 109), and adults (t = −3.29, P < 0.01, df = 33). In children there was a significant interaction between age and CRP, such that in younger children CRP was associated with shorter stature, but in older children was associated with greater stature (t = 2.15, P = 0.04, df = 109).
Conclusions
These results suggest that infection with helminths may have hidden costs associated with immunological changes, and that these costs may ultimately affect growth and other life history parameters.
doi:10.1002/ajhb.21092
PMCID: PMC4512836  PMID: 20865759
3.  Perceived Discrimination and Markers of Cardiovascular Risk among Low-Income African American Youth 
Objectives
Our study examines the relationship between perceived discrimination and levels of C-reactive Protein and blood pressure in low-income youth ages 10–15 years old.
Methods
Data were collected from 10–15 year old focal children and their mothers. Face-to-face interviews were implemented to collect data on stressors including experiences of everyday discrimination from youth. High sensitivity CRP in dried blood spot samples and diastolic and systolic blood pressure were also collected at the time of the interview.
Results
Perceived discrimination among youth was significantly associated with higher levels of CRP, systolic and diastolic blood pressure. CRP, systolic, and diastolic blood pressure remained significant after controlling for age-adjusted BMI, waist circumference, and other factors.
Conclusion
Discrimination is a salient risk factor for inflammation and cardiovascular health. Early life course inflammation and cardiovascular reactivity are important candidate pathways through which the repeated exposure to discrimination for minority group members contributes to racial and economic health inequities in adulthood.
doi:10.1002/ajhb.22683
PMCID: PMC4478198  PMID: 25753652
C-reactive protein; discrimination; blood pressure; adolescent; health disparities
4.  Human Linear Growth Trajectory Defined 
Objectives
The purpose of this study was to assess the applicability of a simple mathematical formula for prediction of individual child linear growth. The formula describes a square root dependence of height on age with only two constants, k and C.
Methods
Retrospective serial height measurements of 137 healthy children (61 female), who attended clinic in the Pediatrics Department at the University of California, San Francisco were used. For each child, two of the initial measurements and their corresponding measurement times were used to determine the values of k and C. By substituting the determined values of k and C into the formula, the formula was then used to predict the trajectory of the child’s growth.
Results
The 137 children were comprised of 20% Hispanic, 23% African-American, 27% Caucasian and 30% Asian. The formula predicted growth trajectories of 136 out of the 137 children with minimal discrepancies between the measured data and the corresponding predicted data. The mean of the discrepancies was 0.8 cm.
Conclusions
Our proposed formula is very easy to use and predicts individual child growth with high precision irrespective of gender or ethnicity. The formula will be a valuable tool for studying human growth and possibly growths of other animals.
doi:10.1002/ajhb.22428
PMCID: PMC4489416  PMID: 23934960
5.  Blood Cell Telomere Lengths and Shortening Rates of Chimpanzee and Human Females 
Objectives
Slower rates of aging distinguish humans from our nearest living cousins. Chimpanzees rarely survive their forties while large fractions of women are postmenopausal even in high-mortality hunter–gatherer populations. Cellular and molecular mechanisms for these somatic aging differences remain to be identified, though telomeres might play a role. To find out, we compared telomere lengths across age-matched samples of female chimpanzees and women.
Methods
We used a monochrome multiplex quantitative polymerase chain reaction to assay canonical telomere repeats in blood cells from captive female chimpanzees (65 individuals; age: 6.2–56.7 years) and compared them to the same measure in human females (43 individuals; age: 7.4–57.3 years).
Results
Our samples showed little difference in attrition rates between the species (~0.022 T/S per year for chimpanzees and ~0.012 T/S per year for humans with overlapping 95% confidence intervals), but telomeres were twice as long in chimpanzees as in humans (T/S ratios = 2.70 and 1.26, respectively).
Conclusions
Based on the longevity differences, we initially hypothesized that telomere shortening rates would be faster in chimpanzees than in humans. Instead, it is shorter telomere length that appears to be the derived state in humans. This comparison indicates that better characterization of physiological aging in our closest living relatives will be indispensable for understanding the evolution of distinctive human longevity.
doi:10.1002/ajhb.22538
PMCID: PMC4352344  PMID: 24633909
6.  Correlation Analysis of Genetic Admixture and Social Identification with Body Mass Index in a Native American Community 
Objectives
Body mass index (BMI) is a well-known measure of obesity with a multitude of genetic and non-genetic determinants. Identifying the underlying factors associated with BMI is difficult because of its multifactorial etiology that varies as a function of geoethnic background and socioeconomic setting. Thus, we pursued a study exploring the influence of the degree of Native American admixture on BMI (as well as weight and height individually) in a community sample of Native Americans (n=846) while accommodating a variety of socioeconomic and cultural factors.
Methods
Participants’ degree of Native American (NA) ancestry was estimated using a genome-wide panel of markers. The participants also completed an extensive survey of cultural and social identity measures: the Indian Culture Scale (ICS) and the Orthogonal Cultural Identification Scale (OCIS). Multiple linear regression was used to examine the relation between these measures and BMI.
Results
Our results suggest that BMI is correlated positively with the proportion of NA ancestry. Age was also significantly associated with BMI, while gender and socioeconomic measures (education and income) were not. For the two cultural identity measures, the ICS showed a positive correlation with BMI, while OCIS was not associated with BMI.
Conclusions
Taken together, these results suggest that genetic and cultural environmental factors, rather than socioeconomic factors, account for a substantial proportion of variation in BMI in this population. Further, significant correlations between degree of NA ancestry and BMI suggest that admixture mapping may be appropriate to identify loci associated with BMI in this population.
doi:10.1002/ajhb.22521
PMCID: PMC4068510  PMID: 24757035
Genetic ancestry; admixture; body habitus; obesity; Native Americans
7.  Mitochondrial Variation among the Aymara and the Signatures of Population Expansion in the Central Andes 
Objectives
The exploitation of marine resources and intensive agriculture led to a marked population increase early in central Andean prehistory. Constant historic and prehistoric population movements also characterize this region. These features undoubtedly affected regional genetic variation, but the exact nature of these effects remains uncertain.
Methods
Mitochondrial DNA (mtDNA) hypervariable region I sequence variation in 61 Aymara individuals from La Paz, Bolivia, was analyzed and compared to sequences from 47 other South American populations to test hypotheses of whether increased female effective population size and gene flow influenced the mtDNA variation among central Andean populations.
Results
The Aymara and Quechua were genetically diverse showing evidence of population expansion and large effective population size, and a demographic expansion model fits the mtDNA variation found among central Andean populations well. Estimated migration rates and the results of AMOVA and multidimensional scaling analysis suggest that female gene flow was also an important factor, influencing genetic variation among the central Andeans as well as lowland populations from western South America. mtDNA variation in south central Andes correlated better with geographic proximity than with language, and fit a population continuity model.
Conclusion
The mtDNA data suggests that the central Andeans experienced population expansion, most likely because of rapid demographic expansion after introduction of intensive agriculture, but roles of female gene flow need to be further explored.
doi:10.1002/ajhb.22507
PMCID: PMC4289594  PMID: 24449040
8.  Ovarian Function in Samoan Women Shows Stronger Association with Signals of Energy Metabolism than Fat Reserves 
Objectives
The relative influence of prominent energetic hormones such as insulin and leptin on ovarian steroid production has yet to be determined and demonstrated consistently in vivo. This study reports preliminary findings on the relationship between insulin, leptin, and estradiol, a major ovarian steroid, in a sample of Samoan women.
Methods
Participants were 34 regularly cycling, premenopausal women in the follicular phase of their menstrual cycle with indicators of normal glucose tolerance. Fasting serum samples provided one-time, cross-sectional measures of glucose, insulin, leptin, and estradiol. Main statistical analyses consisted of Student's t-tests, used to determine significant differences in mean estradiol level between contrasting groups of insulin and leptin.
Results
Relatively high insulin levels within the normal range of variation showed a positive association with estradiol levels whereas relatively high leptin levels did not. The relationship between insulin and estradiol appeared to conform to a step-like categorical function -- with the highest insulin levels exerting the greatest positive effect -- rather than a dose-response linear function.
Conslusions
The current study adds to the growing evidence that peripheral regulation of ovarian function likely involves permissive signals that emphasize a state of energy surplus, related primarily to energy metabolism rather than energy reserves, and warrant more extensive study.
doi:10.1002/ajhb.22465
PMCID: PMC4403792  PMID: 24375833
ovarian function; estradiol; insulin; leptin; energetics; Samoa
9.  Exploring secular changes in the association between BMI and waist circumference in Mexican-origin and white women: a comparison of Mexico and the United States 
Objectives
BMI and waist circumference (WC) tend to be highly correlated, but changes in lifestyle behaviors may promote greater accumulation of abdominal fat for the same BMI in recent years. We examined secular shifts in BMI and WC distributions, and investigated whether WC for a given BMI has changed over time among Mexican-origin women in Mexico and the U.S., and in U.S. white women as a comparison.
Methods
Nationally-representative surveys for women aged 20-49 years from Mexico (1988, 1999, and 2012) (n=37116) and the US (1988-1994, 1999-2002, and 2007-2010) (n=6985) were used. Quantile regressions estimated age-adjusted changes in BMI and WC across years; linear regression tested changes in mean WC over time, adjusting for age and BMI.
Results
In all women, BMI and WC at most centiles increased over time. WC was also significantly higher over time for the same BMI, though the increase was largest in Mexican women. For example, WC was 6.7 cm (standard error (SE): 0.17, p<0.0001) higher in 2012 than in 1999 among Mexican women, holding age and BMI constant. Estimates were smaller in magnitude for Mexican-American and white women (~3 cm, p<0.01), even when comparing over a longer timeframe (1988-1994 to 2007-2010). In all groups, WC adjusted for BMI increased to a larger extent among younger cohorts.
Conclusion
WC for the same BMI has increased in Mexican-American, white, and Mexican women of reproductive age. These patterns may have implications for future cardio-metabolic burden in Mexico and the US.
doi:10.1002/ajhb.22573
PMCID: PMC4138229  PMID: 24917415
obesity; population; epidemiology; women; ethnicity
10.  The Origins and Genetic Distinctiveness of the Chamorros of the Marianas Islands: An mtDNA Perspective 
Background
Archaeological and linguistic evidence suggests the Marianas Islands were settled around 3,600 years before present (ybp) from Island Southeast Asia (ISEA). Around 1,000 ybp latte stone pillars and the first evidence of rice cultivation appear in the Marianas. Both traditions are absent in the rest of prehistoric Oceania.
Objective
To examine the genetic origins and postsettlement gene flow of Chamorros of the Marianas Islands.
Methods
To infer the origins of the Chamorros we analyzed ~360 base pairs of the hypervariable-region 1 (HVS1) of mitochondrial DNA from 105 Chamorros from Guam, Rota, and Saipan, and the complete mitochondrial genome of 32 Guamanian Chamorros, and compared them to lineages from ISEA and neighboring Pacific archipelagoes from the database.
Results
Results reveal that 92% of Chamorros belong to haplogroup E, also found in ISEA but rare in Oceania. The two most numerous E lineages were identical to lineages currently found in Indonesia, while the remaining E lineages differed by only one or two mutations and all were unique to the Marianas. Seven percent of the lineages belonged to a single Chamorro-specific lineage within haplogroup B4, common to ISEA as well as Micronesia and Polynesia.
Conclusions
These patterns suggest a small founding population had reached and settled the Marianas from ISEA by 4,000 ybp, and developed unique mutations in isolation. A second migration from ISEA may have arrived around 1,000 ybp, introducing the latte pillars, rice agriculture and the homogeneous minority B4 lineage.
doi:10.1002/ajhb.22349
PMCID: PMC4335639  PMID: 23180676
11.  Quantifying Calcium Intake in School Age Children: Development and Validation of the Calcium Counts!© Food Frequency Questionnaire 
Quantifying dietary behavior is difficult and can be intrusive. Calcium, an essential mineral for skeletal development during childhood, is difficult to assess. Few studies have examined the use of food frequency questionnaires (FFQs) for assessing calcium intake in school-age children. This study evaluated the validity and reliability of the Calcium Counts!© FFQ (CCFFQ) for estimating calcium intake in school children in the US. Healthy children, aged 7–10 years (n = 139) completed the CCFFQ and 7-day weighed food records. A subset of subjects completed a second CCFFQ within 3.6 months. Concurrent validity was determined using Pearson correlations between the CCFFQ and food record estimates of calcium intake, and the relationship between quintiles for the two measures. Predictive validity was determined using generalized linear regression models to explore the effects of age, race, and gender. Inter- and intra-individual variability in calcium intake was high (>300 mg/day). Calcium intake was ~300 mg/day higher by CCFFQ compared to food records. Concurrent validity was moderate (r = 0.61) for the entire cohort and higher for selected subgroups. Predictive validity estimates yielded significant relationships between CCFFQ and food record estimates of calcium intake alone and in the presence of such potential effect modifiers as age group, race, and gender. Test–retest reliability was high (r = 0.74). Although calcium intake estimated by the CCFFQ was greater than that measured by food records, the CCFFQ provides valid and reliable estimates of calcium intake in children. The CCFFQ is especially well-suited as a tool to identify children with low calcium intakes.
doi:10.1002/ajhb.20975
PMCID: PMC4334123  PMID: 19621431
12.  The Effects of Market Integration on Childhood Growth and Nutritional Status: the Dual Burden of Under- and Over-Nutrition in the Northern Ecuadorian Amazon 
Objectives
Market integration is an important source of cultural change exposing indigenous populations to epidemiologic and nutrition transitions. As children and adolescents are biologically sensitive to the health effects of market integration, we examine community variation of anthropometric indicators of nutritional status and growth among a cross-cultural sample of Kichwa, Shuar, Huaorani and Cofán indigenous groups in the northern Ecuadorian Amazon.
Methods
We measured height, weight, body mass index (BMI), upper arm circumference and triceps skinfolds of 186 children and adolescents aged two to 18 years from seven communities. Anthropometric z-scores were calculated based on the National Health and Nutritional Examination Survey. Comparisons were made to this US reference group, along with between community differences to contextually explore the impacts of varying degrees of market integration.
Results
We found a high prevalence of stunting in both boys (40%) and girls (34%). Adiposity increased with age and 40% of girls between 15 and 18 years old were overweight. There were large sex differences in body composition with higher BMI, arm circumference and triceps skinfolds in adolescent girls. The Kichwa demonstrated the poorest growth outcomes and nutritional stress followed by the Huaorani and Shuar; yet distinctions in under- and over-nutrition were evident within groups.
Conclusion
Market integration is a major factor influencing the developmental and lifestyle mismatch associated with the epidemiologic and nutrition transition in general, and the dual burden pattern of high rates of stunting yet adequate to above average short-term nutritional status indicators found among indigenous Amazonian populations.
doi:10.1002/ajhb.22404
PMCID: PMC4331102  PMID: 23657874
indigenous health; stunting; overweight; nutrition transition
13.  Interrelationships Between Anthropometric Variables and Overweight in Childhood and Adolescence 
American Journal of Human Biology  2014;26(4):502-510.
Objectives
To answer the questions: how does body mass index (BMI) correlate to five overweight related anthropometric variables during different ages in childhood, and which anthropometric variables contribute most to variation in BMI during childhood?
Methods
Data on BMI, height (H), sitting height (SH), waist circumference (WC), waist to height ratio (WHtR), waist to sitting height ratio (WSHtR), subscapular skinfold (SSF), and triceps skinfold (TSF), from 4,576 Norwegian children 4.00–15.99 years of age, were transformed to standard deviation scores (SDS) and studied using correlation and multiple regression analyses.
Results
The correlations between BMI SDS and the standardized anthropometric variables were in general strong and positive. For all variables, the correlations were weakest in the youngest age group and highest between 7 and 12 years. WC SDS and WHtR SDS were most strongly correlated with BMI SDS through all ages and in both sexes. A model with seven anthropometric variables adjusted for age and sex explained 81.4% of the variation in BMI SDS. When adjusted for all other variables, WC SDS contributed most to the variation in BMI SDS (b = 0.467, CI [0.372, 0.562]). Age group, but not sex, contributed significantly to variation in BMI SDS.
Conclusion
The interrelationships between BMI SDS and five standardized overweight related anthropometric variables were dependent on age, being weakest in the youngest age group. Independent of sex and age, WC SDS was in this study superior to other anthropometric variables in contributing to variation in BMI SDS during childhood. Am. J. Hum. Biol. 26:502–510, 2014. © 2014 The Authors American Journal of Human Biology Published by Wiley Periodicals, Inc.
doi:10.1002/ajhb.22554
PMCID: PMC4329336  PMID: 24782200
14.  Postnatal Growth Velocity and Overweight in Early Adolescents: A Comparison of Rural and Urban African Boys and Girls 
American Journal of Human Biology  2014;26(5):643-651.
Objectives
To compare growth velocity of two African child cohorts and examine the relationship between postnatal growth velocity in infancy/early childhood and the risk of overweight/stunting in early adolescence.
Methods
The study used data from two child cohorts from urban (Birth to Twenty Cohort, South Africa) and rural (Lungwena Child Survival Study, Malawi) African settings. Mixed effect modelling was used to derive growth and peak growth velocities. T-tests were used to compare growth parameters and velocities between the two cohorts. Linear and logistic regression models were used to determine the relationship between growth velocity and early adolescent (ages 9–11 years) body mass index and odds of being overweight.
Results
Children in the BH cohort were significantly taller and heavier than those in the Lungwena cohort, and exhibited faster weight and height growth velocity especially in the first year of life (P < 0.05). No significant association was shown between baseline weight (αw) and overweight in early adolescence (OR = 1.25, CI = 0.67, 2.34). The weight growth velocity parameter βw was highly associated with odds of being overweight. Association between overweight in adolescence and weight velocity was stronger in infancy than in early childhood (OR at 3 months = 4.80, CI = 2.49, 9.26; OR at 5 years = 2.39, CI = 1.65, 3.47).
Conclusion
High weight and height growth velocity in infancy, independent of size at birth, is highly associated with overweight in early adolescence. However, the long term effects of rapid growth in infancy may be dependent on a particular population's socio-economic status and level of urbanization. Am. J. Hum. Biol. 26:643–651, 2014. © 2014 The Authors American Journal of Human Biology Published by Wiley Periodicals, Inc.
doi:10.1002/ajhb.22575
PMCID: PMC4329380  PMID: 24948025
15.  [No title available] 
PMCID: PMC4292846  PMID: 24799123
16.  Pathogenic and Obesogenic Factors Associated with Inflammation in Chinese Children, Adolescents and Adults 
Objectives
Influenced by pathogen exposure and obesity, inflammation provides a critical biological pathway linking changing environments to the development of cardiometabolic disease. This study tests the relative contribution of obesogenic and pathogenic factors to moderate and acute CRP elevations in Chinese children, adolescents and adults.
Methods
Data come from 8795 participants in the China Health and Nutrition Study. Age-stratified multinomial logistic models were used to test the association between illness history, pathogenic exposures, adiposity, health behaviors and moderate (1-10 mg/L in children and 3-10 mg/L in adults) and acute (>10mg/L) CRP elevations, controlling for age, sex and clustering by household. Backward model selection was used to assess which pathogenic and obesogenic predictors remained independently associated with moderate and acute CRP levels when accounting for simultaneous exposures.
Results
Overweight was the only significant independent risk factor for moderate inflammation in children (RRR 2.10, 95%CI 1.13-3.89). History of infectious (RRR 1.28, 95%CI 1.08-1.52) and non-communicable (RRR 1.37, 95%CI 1.12-1.69) disease, overweight (RRR 1.66, 95%CI 1.45-1.89) and high waist circumference (RRR 1.63, 95%CI 1.42-1.87) were independently associated with a greater likelihood of moderate inflammation in adults while history of infectious disease (RRR 1.87, 95%CI 1.35-2.56) and overweight (RRR 1.40, 95%CI 1.04-1.88) were independently associated with acute inflammation. Environmental pathogenicity was associated with a reduced likelihood of moderate inflammation, but a greater likelihood of acute inflammation in adults.
Conclusions
These results highlight the importance of both obesogenic and pathogenic factors in shaping inflammation risk in societies undergoing nutritional and epidemiological transitions.
doi:10.1002/ajhb.22462
PMCID: PMC3932143  PMID: 24123588
C-reactive protein; Inflammation; Obesity; Infectious Disease; China; Life course
17.  Prenatal and postnatal energetic conditions and sex steroids levels across the first year of life 
Objectives
Human biologists have documented variability in reproductive maturation, fertility, and cancer risk related to developmental conditions. Yet no previous studies have directly examined the impact of pre- and post-natal energetic environments on sex steroids in infancy, a critical period for hypothalamic-pituitary-gonadal axis development. Thus, we examined the impact of maternal characteristics, birth size, and feeding practices on fecal sex steroid production in a longitudinal sample of 31 American infants followed from 2 weeks to 12 months of age.
Methods
Maternal characteristics and birth size were collected at study enrollment, infant diet was assessed through weekly 24-hr food diaries, and anthropometrics were measured weekly. Fecal estradiol and testosterone levels were assessed weekly using validated microassay RIA techniques. Mixed models were used to test for associations between maternal and birth characteristics, feeding practices, and sex steroids across the first year of life. Formal mediation analysis examined whether the relationship between infant feeding and hormone levels was mediated by infant size.
Results
Maternal and birth characteristics had persistent effects on fecal sex steroid levels, with taller maternal height and larger birth size associated with lower estradiol levels in girls and higher testosterone levels in boys. Infant diet was also associated with sex steroid levels independently of infant size. Formula feeding was associated with higher estradiol levels in boys and girls and with higher testosterone in girls.
Conclusion
These results suggest that markers of early energy availability influence sex hormone levels with potential long-term consequences for reproductive development and function.
doi:10.1002/ajhb.22424
PMCID: PMC4271319  PMID: 23904043
estradiol; testosterone; infancy; infant feeding; birthweight
18.  The anthropometry of children and adolescents may be influenced by the prenatal smoking habits of their grandmothers: A longitudinal cohort study 
American Journal of Human Biology  2014;26(6):731-739.
Objectives
Previously, in the Avon Longitudinal Study of Parents and Children (ALSPAC), we have shown different sex-specific birth anthropometric measurements contingent upon whether or not prenatal smoking was undertaken by paternal grandmother (PGM±), maternal grandmother (MGM±), and the study mother (M±). The findings raised the question as to whether there were long-term associations on the growth of the study children over time.
Methods
Measures of weight, height, body mass index, waist circumference, lean mass, and fat mass of children in the ALSPAC study from 7 to 17 years of age were used. We compared growth in four categories at each age: PGM+M− with PGM−M−; MGM+M− with MGM−M−; PGM+M+ with PGM−M+; MGM+M+ with MGM−M+; and adjusted for housing tenure, maternal education, parity, and paternal smoking at the start of the study pregnancy.
Results
We found that if the PGM had, but the study mother had not, smoked in pregnancy, the girls were taller and both genders had greater bone and lean mass. However, if the MGM had smoked prenatally but the mother had not (MGM+M−), the boys became heavier than expected with increasing age—an association that was particularly due to lean rather than fat mass, reflected in increased strength and fitness. When both the maternal grandmother and the mother had smoked (MGM+M+) girls had reduced height, weight, and fat/lean/bone mass when compared with girls born to smoking mothers whose own mothers had not smoked (MGM−M+).
Conclusions
This study indicates that smoking in humans can have sex-specific transgenerational effects. Am. J. Hum. Biol. 26:731–739, 2014. © 2014 The Authors American Journal of Human Biology Published by Wiley Periodicals, Inc.
doi:10.1002/ajhb.22594
PMCID: PMC4238812  PMID: 25130101
19.  Normalization of elevated cardiac, kidney, and hemolysis plasma markers within 48 h in Mexican Tarahumara runners following a 78 km race at moderate altitude 
American Journal of Human Biology  2014;26(6):836-843.
Objectives
The aim of this study was to examine to what extent extreme endurance exercise results in changes of plasma markers associated with cardiac and renal damage, as well as hemolysis in male, Mexican Tarahumara runners.
Methods
Ten Tarahumara runners (mean (sd) age of 38 (12) years) participated in a 78 km race in Chihuahua, Mexico at 2,400 m above sea level. Cardiac, kidney, and hematology plasma markers were measured pre-race and <5 min, 1 h, 3 h, 6 h, 24 h, and 48 h post-race. Anthropometry, blood pressure, pulse rate, electrocardiography, HbA1c, hemoglobin and VO2max (estimated from heart rate following step test) were assessed pre-race, while physical activity energy expenditure and intensity were estimated during the race, and oxygen partial pressure saturation (SpO2) <30 min post-race.
Results
Estimated mean VO2max was 48 (9) mLO2 min−1 kg−1 and relative intensity during the race was 68 (11)%VO2max. Mean SpO2 was 92 (3)% <30 min post-race. Plasma concentrations of especially total creatine kinase, creatine kinase-MB isoform, and haptoglobin changed significantly from pre-race values (P < 0.001) up to 24 h post-race, but had returned to pre-race values after 48 h. The plasma concentrations of mid-regional proatrial natiuretic peptide and copeptin returned to pre-race concentrations after 1 and 6 h, respectively.
Conclusions
Altered cardiac, renal, and hemolysis plasma markers were normalized after 48 h following 78 km of running, suggesting that the impact of exercise-induced cardiac and kidney damage as well as hemolysis in the Mexican Tarahumara is low. Am. J. Hum. Biol. 26:836–843, 2014. © 2014 The Authors American Journal of Human Biology Published by Wiley Periodicals, Inc.
doi:10.1002/ajhb.22607
PMCID: PMC4237147  PMID: 25145663
20.  Non-Syndromic Brachydactyly Type D and Type E Mapped to 7p15 in Healthy Children and Adults from the Jirel Ethnic Group in Eastern Nepal 
Objectives
There is phenotypic overlap between Brachydactyly Type D (BDD) and Brachydactyly Type E (BDE) that suggests a possible common underlying etiology. We seek to understand the genetic underpinnings of, and relationship between, these skeletal anomalies.
Methods
The Jirel ethnic group of eastern Nepal participates in various genetic epidemiologic studies, including those in which hand-wrist radiographs have been taken to examine skeletal development. 2,130 individuals (969 males; 1,161 females) were phenotyped for BDD/BDE. Of these, 1,722 individuals (773 males; 949 females) were genotyped for 371 STR markers spanning the autosomal genome. Variance components-based linkage analysis was used to conduct a genome-wide linkage scan for QTL influencing the BDD/BDE phenotype.
Results
BDD was present in 3.55%, and BDE was present in 0.39%, of the study sample. Because of the phenotypic overlap between two traits, affecteds of either type were considered as affected by a single combined phenotype (BDD/BDE) having a prevalence of 3.94%. The additive genetic heritability of BDD/BDE was highly significant (h2 ± SE = 0.89 ± 0.13; p = 1.7×10−11). Significant linkage of BDD/BDE was found to markers on chromosome 7p21-7p14 (peak LOD score = 3.74 at 7p15 between markers D7S493 and D7S516).
Conclusions
Possible positional candidate genes in the one-lod support interval of this QTL include TWIST and the HOXA1-A13 cluster. This is the first study to report significant linkage results for BDD/BDE using a large extended pedigree, and the first to suggest that mutations in TWIST and/or the HOXA1-A13 cluster may contribute to these specific skeletal anomalies.
doi:10.1002/ajhb.22441
PMCID: PMC3968259  PMID: 24022874
BDD; BDE; linkage; Chromosome 7
21.  Maternal cortisol disproportionately impacts fetal growth in male offspring: Evidence from the Philippines 
Objectives
Lower birth weight (BW) re-occurs across generations, but the intermediate mechanisms remain poorly understood. One potential pathway involves cortisol, which may be elevated in women born small and in turn could lead to fetal growth restriction in offspring. To test this possibility, we evaluated whether BW predicts hypothalamic-pituitary-adrenal (HPA) function in the non-pregnant state in a cohort of young Filipino women, and whether differences in HPA function predict offspring BW.
Methods
Multiple regression relating maternal BW, adult salivary cortisol profiles and recalled offspring BW (N = 488) among participants of the Cebu Longitudinal Health and Nutrition Survey.
Results
Maternal BW related inversely to evening cortisol in adulthood (p < 0.04). Maternal BW and evening cortisol were both stronger predictors of male than of female BW (maternal BW: p < 0.0001 for males; p = 0.07 for females; bedtime cortisol: p = 0.003 for males; p = 0.3 for females). Waking and thirty minute post-waking cortisol did not predict offspring BW. Controlling for evening cortisol did not diminish the relationship between maternal and offspring BW in males or females.
Conclusions
Being born small predicted higher evening cortisol in adulthood among these young mothers. Lower maternal BW and elevated evening cortisol independently predicted giving birth to lower BW offspring, with effects greatest and only significant among males. We speculate that sex differences in sensitivity to maternal stress hormones could help explain the stronger relationships between BW and CVD risk factors reported among the males in this and other populations.
doi:10.1002/ajhb.21226
PMCID: PMC4181846  PMID: 22121049
cortisol; birth weight; intergenerational effects; sex differences; DOHaD
22.  Wrist Breadth and Homeostasis Model Assessment of Insulin Resistance in Youth: The Fels Longitudinal Study 
Objectives
There is biological crosstalk between insulin signaling and bone remodeling pathways, and wrist circumference and bone area were recently found to associate with insulin resistance independent of body mass index (BMI) in overweight/obese children. We aimed to expand on this work by using more specific measures of adiposity for adjustment and examining children with broader range of BMI.
Methods
We used serial data (1,051 total measures) on 313 non-Hispanic white youth (ages 8–18 y) from the Fels Longitudinal Study with homeostasis model assessment of insulin resistance (HOMA-IR) as the outcome. Internal standard deviation score (SDS) for wrist breadth was evaluated as a predictor of HOMA-IR (log-transformed) before and after adjusting for internal-sample SDSs for BMI, waist circumference (WC), and total body fat (TBF) from dual energy X-ray absorptiometry, in addition to age, sex, Tanner stage, and birth year, using generalized estimating equations.
Results
Before additional adiposity adjustment, we found a significant positive association between wrist breadth SDS and log-transformed HOMA-IR (β = 0.13; 95%CI: 0.09–0.17), which remained significant after adjusting for TBF SDS (β = 0.09; 95%CI: 0.05–0.13; P < 0.001), BMI SDS (β = 0.06; 95%CI: 0.02–0.10; P = 0.007), and WC SDS (β = 0.06; 95%CI: 0.02–0.09; P = 0.005).
Conclusions
Further work is needed to determine whether simple frame size measures such as wrist breadth may be useful markers of metabolic risk.
doi:10.1002/ajhb.22416
PMCID: PMC3988662  PMID: 23897560
23.  Evidence for novel genetic loci associated with metabolic traits in Yup’ik people 
Objectives:
To identify genomic regions associated with fasting plasma lipid profiles, insulin, glucose, and glycosylated hemoglobin in a Yup’ik study population, and to evaluate whether the observed associations between genetic factors and metabolic traits were modified by dietary intake of marine derived omega-3 polyunsaturated acids (n-3 PUFA).
Methods:
A genome-wide linkage scan was conducted among 982 participants of the Center for Alaska Native Health Research study. n-3 PUFA intake was estimated using the nitrogen stable isotope ratio (δ15N) of erythrocytes. All genotyped SNPs located within genomic regions with LOD scores > 2 were subsequently tested for individual SNP associations with metabolic traits using linear models that account for familial correlation as well as age, sex, community group and n-3 PUFA intake. Separate linear models were fit to evaluate interactions between the genotype of interest and n-3 PUFA intake.
Results:
We identified several chromosomal regions linked to serum apolipoprotein A2, high density lipoprotein-, low density lipoprotein-, and total cholesterol, insulin, and glycosylated hemoglobin. Genetic variants found to be associated with total cholesterol mapped to a region containing previously validated lipid loci on chromosome 19, and additional novel peaks of biological interest were identified at 11q12.2-11q13.2. We did not observe any significant interactions between n-3 PUFA intake, genotypes, and metabolic traits.
Conclusions:
We have completed a whole genome linkage scan for metabolic traits in Native Alaskans, confirming previously identified loci, and offering preliminary evidence of novel loci implicated in chronic disease pathogenesis in this population.
doi:10.1002/ajhb.22429
PMCID: PMC3785243  PMID: 23907821
Alaska Native; metabolism; multi-point linkage genome scan
24.  Patterns of Senescence in Human Cardiovascular Fitness: VO2max in Subsistence and Industrialized Populations 
Objectives
This study explores whether cardiovascular fitness levels and senescent decline are similar in the Tsimane of Bolivia and Canadians, as well as other subsistence and industrialized populations. Among Tsimane, we examine whether morbidity predicts lower levels and faster decline of cardiovascular fitness, or whether their lifestyle (e.g., high physical activity) promotes high levels and slow decline. Alternatively, high activity levels and morbidity might counterbalance such that Tsimane fitness levels and decline are similar to those in industrialized populations.
Methods
Maximal oxygen uptake (VO2max) was estimated using a step test heart rate method for 701 participants. We compared these estimates to the Canadian Health Measures Survey and previous studies in industrialized and subsistence populations. We evaluated whether health indicators and proxies for market integration were associated with VO2max levels and rate of decline for the Tsimane.
Results
The Tsimane have significantly higher levels of VO2max and slower rates of decline than Canadians; initial evidence suggests differences in VO2max levels between other subsistence and industrialized populations. Low hemoglobin predicts low VO2max for Tsimane women while helminth infection predicts high VO2max for Tsimane men, though results might be specific to the VO2max scaling parameter used. No variables tested interact with age to moderate decline.
Conclusions
The Tsimane demonstrate higher levels of cardiovascular fitness than industrialized populations, but levels similar to other subsistence populations. The high VO2max of Tsimane is consistent with their high physical activity and few indicators of cardiovascular disease, measured in previous studies.
doi:10.1002/ajhb.22445
PMCID: PMC4142762  PMID: 24022886
25.  Seasonal variation of peripheral blood leukocyte telomere length in Costa Rica: a population based observational study 
Objectives
Peripheral blood leukocyte telomere length is increasingly being used as a biomarker of aging, but its natural variation in human populations is not well understood. Several other biomarkers show seasonal variation, as do several determinants of leukocyte telomere length. We examined whether there was monthly variation in leukocyte telomere length in Costa Rica, a country with strong seasonal differences in precipitation and infection.
Methods
We examined a longitudinal population based cohort of 581 Costa Rican adults age 60 and above, from which blood samples were drawn between October 2006 and July 2008. Leukocyte telomere length was assayed from these samples using the quantitative PCR method. Multivariate regression models were used to examine correlations between month of blood draw and leukocyte telomere length.
Results
Telomere length from peripheral blood leukocytes varied by as much as 200 base pairs depending on month of blood draw, and this difference is not likely to be due to random variation. A moderate proportion of this association is statistically accounted for by month and region specific average rainfall. We found shorter telomere length associated with greater rainfall.
Conclusions
There are two possible explanations of our findings. First, there could be relatively rapid month-to-month changes in leukocyte telomere length. This conclusion would have implications for understanding the natural population dynamics of telomere length. Second, there could be seasonal differences in constituent cell populations. This conclusion would suggest that future studies of leukocyte telomere length use methods to account for the potential impact of constituent cell type.
doi:10.1002/ajhb.22529
PMCID: PMC4136920  PMID: 24615938
telomere length; seasonality; lymphocytes; infection; rainfall

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