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1.  Genome-wide associated loci influencing interleukin (IL)-10, IL-1Ra, and IL-6 levels in African Americans 
Immunogenetics  2011;64(5):351-359.
Interleukins (ILs) are key mediators of the immune response and inflammatory process. Plasma levels of IL-10, IL-1Ra, and IL-6 are associated with metabolic conditions, show large inter-individual variations, and are under strong genetic control. Therefore, elucidation of the genetic variants that influence levels of these ILs provides useful insights into mechanisms of immune response and pathogenesis of diseases. We conducted a genome-wide association study (GWAS) of IL-10, IL-1Ra, and IL-6 levels in 707 non-diabetic African Americans using 5,396,780 imputed and directly genotyped single nucleotide polymorphisms (SNPs) with adjustment for gender, age, and body mass index. IL-10 levels showed genome-wide significant associations (p<5×10−8) with eight SNPs, the most significant of which was rs5743185 in thePMS1 gene (p=2.30×10−10). We tested replication of SNPs that showed genome-wide significance in 425 non-diabetic individuals from West Africa, and successfully replicated SNP rs17365948 in the YWHAZ gene (p=0.02). IL-1Ra levels showed suggestive associations with two SNPs in the ASB3 gene (p=2.55×10−7), 10 SNPs in the IL-1 gene family (IL1F5, IL1F8, IL1F10, and IL1Ra, p=1.04×10−6 to 1.75×10−6), and 23 SNPs near the IL1A gene (p=1.22×10−6 to 1.63×10−6). We also successfully replicated rs4251961 (p=0.009); this SNP was reported to be associated with IL-1Ra levels in a candidate gene study of Europeans. IL-6 levels showed genome-wide significant association with one SNP (RP11-314E23.1; chr6:133397598; p=8.63×10−9). To our knowledge, this is the first GWAS on IL-10, IL-1Ra, and IL-6 levels. Follow-up of these findings may provide valuable insight into the pathobiology of IL actions and dysregulations in inflammation and human diseases.
PMCID: PMC3418332  PMID: 22205395
interleukin; interleukin-10; interleukin-1Ra; interleukin-6; genome-wide association study; African American
2.  Parasitological, serological, and clinical evidence for high prevalence of podoconiosis (non-filarial elephantiasis) in Midakegn district, central Ethiopia 
Both podoconiosis (a geochemical non-filarial disease) and chronic filarial disease result in lower limb elephantiasis. The aims of the present study were to determine whether the elephantiasis in Midakegn district, central Ethiopia is filarial or non-filarial (podoconiosis) using serological, parasitological, and clinical examinations, and to estimate its prevalence.
House-to-house visits were made in 330 randomly selected households. All household members that had elephantiasis were interviewed and clinically examined at the nearby health center to confirm presence of elephantiasis, check presence of scrotal swelling, and rule out other causes of lymphoedema. Midnight blood sample was obtained from each participant with elephantiasis for microscopic examination of W. bancrofti microfilaria. Day time blood sample was obtained from half of the participants for serological confirmation using the immuno-chromatographic test card.
Consistent with features of podoconiosis (non-filarial elephantiasis), none of the elephantiasis cases had consistently worn shoes since childhood; 94.3% had bilateral swelling limited below the level of the knees; no individual had thigh or scrotal elephantiasis; parasitological test for microfilariae and serological tests for W. bancrofti antigen turned negative in all samples. The prevalence of the disease was 7.4%. Prevalence peaked in the third decade of life, which also includes the most economically active age groups.
This study has shown high prevalence of podoconiosis (endemic non-filarial elephantiasis) and absence of filarial elephantiasis in Midakegn district. Prevention, treatment, and control of podoconiosis must be among the top priorities of public health programs in the district.
PMCID: PMC3433590  PMID: 22487446
Podoconiosis; Non-filarial elephantiasis; Prevalence; Wuchereria bancrofti; Serology; Ethiopia
3.  Tailoring Information Provision and Consent Processes to Research Contexts: The Value of Rapid Assessments 
Guidance requires that consent processes for research be appropriately tailored to their cultural context. This paper discusses the use of rapid assessments to identify cultural and ethical issues arising when explaining research in studies in The Gambia and Ethiopia. The assessments provided insights into appropriate ways of providing information to minimize the risk of stigmatizing vulnerable research populations; research participants’ views about the most important information to provide about research and their understandings of research; and perceived constraints upon reaching voluntary decisions about participation. These insights demonstrate that rapid assessments are a relatively quick and inexpensive intervention that can provide valuable information to assist in the tailoring of information provision and consent processes to research context while maintaining and enhancing participants’ fundamental protections.
PMCID: PMC3427649  PMID: 22378133
consent; research ethics; empirical research; Africa; The Gambia; Ethiopia
4.  HLA Class II Locus and Susceptibility to Podoconiosis 
The New England Journal of Medicine  2012;366(13):1200-1208.
Podoconiosis is a tropical lymphedema resulting from long-term barefoot exposure to red-clay soil derived from volcanic rock. The World Health Organization recently designated it as a neglected tropical disease. Podoconiosis develops in only a subgroup of exposed people, and studies have shown familial clustering with high heritability (63%).
We conducted a genomewide association study of 194 case patients and 203 controls from southern Ethiopia. Findings were validated by means of family-based association testing in 202 family trios and HLA typing in 94 case patients and 94 controls.
We found a genomewide significant association of podoconiosis with the single-nucleotide polymorphism (SNP) rs17612858, located 5.8 kb from the HLA-DQA1 locus (in the allelic model: odds ratio, 2.44; 95% confidence interval [CI], 1.82 to 3.26; P = 1.42×10−9; and in the additive model: odds ratio, 2.19; 95% CI, 1.66 to 2.90; P = 3.44×10−8), and suggestive associations (P<1.0×10−5) with seven other SNPs in or near HLA-DQB1, HLA-DQA1, and HLA-DRB1. We confirmed these associations using family-based association testing. HLA typing showed the alleles HLA-DRB1*0701 (odds ratio, 2.00), DQA1*0201 (odds ratio, 1.91), and DQB1*0202 (odds ratio, 1.79) and the HLA-DRB1*0701–DQB1*0202 haplotype (odds ratio, 1.92) were risk variants for podoconiosis.
Association between variants in HLA class II loci with podoconiosis (a noncommuni-cable disease) suggests that the condition may be a T-cell–mediated inflammatory disease and is a model for gene–environment interactions that may be relevant to other complex genetic disorders. (Funded by the Wellcome Trust and others.)
PMCID: PMC3350841  PMID: 22455414
5.  Correction: Prediction of HLA Class II Alleles Using SNPs in an African Population 
PLoS ONE  2012;7(7):10.1371/annotation/3529a6a2-4ba2-47dc-929e-399d441b0afa.
PMCID: PMC3393640
6.  Prediction of HLA Class II Alleles Using SNPs in an African Population 
PLoS ONE  2012;7(6):e40206.
Despite the importance of the human leukocyte antigen (HLA) gene locus in research and clinical practice, direct HLA typing is laborious and expensive. Furthermore, the analysis requires specialized software and expertise which are unavailable in most developing country settings. Recently, in silico methods have been developed for predicting HLA alleles using single nucleotide polymorphisms (SNPs). However, the utility of these methods in African populations has not been systematically evaluated.
Methodology/Principal Findings
In the present study, we investigate prediction of HLA class II (HLA-DRB1 and HLA-DQB1) alleles using SNPs in the Wolaita population, southern Ethiopia. The subjects comprised 297 Ethiopians with genome-wide SNP data, of whom 188 had also been HLA typed and were used for training and testing the model. The 109 subjects with SNP data alone were used for empirical prediction using the multi-allelic gene prediction method. We evaluated accuracy of the prediction, agreement between predicted and HLA typed alleles, and discriminative ability of the prediction probability supplied by the model. We found that the model predicted intermediate (two-digit) resolution for HLA-DRB1 and HLA-DQB1 alleles at accuracy levels of 96% and 87%, respectively. All measures of performance showed high accuracy and reliability for prediction. The distribution of the majority of HLA alleles in the study was similar to that previously reported for the Oromo and Amhara ethnic groups from Ethiopia.
We demonstrate that HLA class II alleles can be predicted from SNP genotype data with a high level of accuracy at intermediate (two-digit) resolution in an African population. This finding offers new opportunities for HLA studies of disease epidemiology and population genetics in developing countries.
PMCID: PMC3386230  PMID: 22761960

Results 1-6 (6)