Amerindian-specific regions under positive selection harbour new lipid variants in Latinos

• DOI: 10.1038/ncomms4983
• Publication Date: 2014-06-02T13:28:18Z
• Authors: Arthur Ko; Rita M. Cantor; Daphna Weissglas-...; Elina Nikkola; Prasad M. V. Ling...; Janet S. Sinsheimer; Bogdan Pasaniuc; Robert Brown; Marcus Alvarez; Alejandra Rodriguez; Rosario Rodriguez...; Ivette C. Bautista; Olimpia Arellano-...; Linda L. Muñoz-He...; Veikko Salomaa; Jaakko Kaprio; Antti Jula; Matti Jauhiainen; Markku Heliövaara; Olli Raitakari; Terho Lehtimäki; Johan G. Eriksson; Markus Perola; Kirk E. Lohmueller; Niina Matikainen; Marja-Riitta Task...; Maribel Rodriguez...; Laura Riba; Teresa Tusie-Luna; Carlos A. Aguilar...; Päivi Pajukanta
• Keywords: Dyslipidemia; Genome-wide Association Study

Dyslipidemia and obesity are especially prevalent in populations with Amerindian backgrounds, such as Mexican–Americans, which predispose these to cardiovascular disease. Here we design an approach, known the cross-population allele screen (CPAS), conduct prior a genome-wide association study (GWAS) 19,273 Europeans Mexicans, order identify risk genes Mexicans. Utilizing CPAS restrict GWAS input variants only those differing frequency between two populations, novel lipid genes, receptor-related orphan receptor alpha (RORA) salt-inducible kinase 3 (SIK3), three loci previously unassociated dyslipidemia or obesity. We also detect lipoprotein lipase (LPL) apolipoprotein A5 (APOA5) harbouring specific signatures of haplotypes. Notably, observe that SIK3 one locus underwent positive selection Furthermore, after high-fat meal, variant carriers display high triglyceride levels. These findings suggest Amerindian-specific genetic architecture leads higher incidence modern have prevalence Mexican–Americans. Here, authors approach Mexicans five genomic loci, include RORA SIK3that may contribute populations.