A genome-wide association study of asthma symptoms in Latin American children

Abstract\ud \ud Background\ud Asthma is a chronic disease of the airways and, despite the advances in the knowledge of associated genetic regions in recent years, their mechanisms have yet to be explored. Several genome-wide association studies have been carried out in recent years, but none of these have involved Latin American populations with a high level of miscegenation, as is seen in the Brazilian population.\ud \ud \ud Methods\ud 1246 children were recruited from a longitudinal cohort study in Salvador, Brazil. Asthma symptoms were identified in accordance with an International Study of Asthma and Allergies in Childhood (ISAAC) questionnaire. Following quality control, 1 877 526 autosomal SNPs were tested for association with childhood asthma symptoms by logistic regression using an additive genetic model. We complemented the analysis with an estimate of the phenotypic variance explained by common genetic variants. Replications were investigated in independent Mexican and US Latino samples.\ud \ud \ud Results\ud Two chromosomal regions reached genome-wide significance level for childhood asthma symptoms: the 14q11 region flanking the DAD1 and OXA1L genes (rs1999071, MAF 0.32, OR 1.78, 95 % CI 1.45–2.18, p-value 2.83 × 10−8) and 15q22 region flanking the FOXB1 gene (rs10519031, MAF 0.04, OR 3.0, 95 % CI 2.02–4.49, p-value 6.68 × 10−8 and rs8029377, MAF 0.03, OR 2.49, 95 % CI 1.76–3.53, p-value 2.45 × 10−7). eQTL analysis suggests that rs1999071 regulates the expression of OXA1L gene. However, the original findings were not replicated in the Mexican or US Latino samples.\ud \ud \ud Conclusions\ud We conclude that the 14q11 and 15q22 regions may be associated with asthma symptoms in childhood.This work was supported by the Department of Science and Technology\ud (DECIT, Ministry of Health), National Fund for Scientific and Technological\ud Development (FNDCT, Ministry of Science and Technology), Funding of\ud Studies and Projects (FINEP, Ministry of Science and Technology, Brazil), the\ud Brazilian National Research Council (CNPq) and the Wellcome Trust UK, Ref\ud 072405/Z/03/Z.\ud E.G.B. was funded by grants from National Institutes of Health (HL088133,\ud HL078885, HL004464, HL104608, HL117004, ES015794 and MD006902) and\ud by the American Asthma Foundation, the Sandler Foundation and the RWJF\ud Amos Medical Faculty Development Award.\ud Supported in part by the Intramural Research Program of the NIH, National\ud Institute of Environmental Health Sciences, USA

Universal genome-wide association studies: Powerful joint ancestry and association testing

Summary: The vast majority of human populations and individuals have mixed ancestry. Consequently, adjustment for locus-specific ancestry is essential for genetic association studies. To empower association studies for all populations, it is necessary to integrate effects of locus-specific ancestry and genotype. We developed a joint test of ancestry and association that can be performed with summary statistics, is independent of study design, can take advantage of locus-specific ancestry effects to boost power in association testing, and can utilize association effects to fine map admixture peaks. We illustrate the test using the association between serum triglycerides and LPL. By combining data from African Americans, European Americans, and West Africans, we identify three conditionally independent variants with varying amounts of ancestrally differentiated allele frequencies. Using out-of-sample data, we demonstrate improved prediction achievable by accounting for multiple causal variants and locus-specific ancestry effects at a single locus

Genetic differentiation in East African ethnicities and its relationship with endurance running success.

Since the 1960s, East African athletes, mainly from Kenya and Ethiopia, have dominated long-distance running events in both the male and female categories. Further demographic studies have shown that two ethnic groups are overrepresented among elite endurance runners in each of these countries: the Kalenjin, from Kenya, and the Oromo, from Ethiopia, raising the possibility that this dominance results from genetic or/and cultural factors. However, looking at the life history of these athletes or at loci previously associated with endurance athletic performance, no compelling explanation has emerged. Here, we used a population approach to identify peaks of genetic differentiation for these two ethnicities and compared the list of genes close to these regions with a list, manually curated by us, of genes that have been associated with traits possibly relevant to endurance running in GWAS studies, and found a significant enrichment in both populations (Kalenjin, P = 0.048, and Oromo, P = 1.6x10-5). Those traits are mainly related to anthropometry, circulatory and respiratory systems, energy metabolism, and calcium homeostasis. Our results reinforce the notion that endurance running is a systemic activity with a complex genetic architecture, and indicate new candidate genes for future studies. Finally, we argue that a deterministic relationship between genetics and sports must be avoided, as it is both scientifically incorrect and prone to reinforcing population (racial) stereotyping