A1 Refereed original research article in a scientific journal
Amerindian-specific regions under positive selection harbour new lipid variants in Latinos
Authors: Ko A, Cantor RM, Weissglas-Volkov D, Nikkola E, Reddy PMVL, Sinsheimer JS, Pasaniuc B, Brown R, Alvarez M, Rodriguez A, Rodriguez-Guillen R, Bautista IC, Arellano-Campos O, Munoz-Hernandez LL, Salomaa V, Kaprio J, Jula A, Jauhiainen M, Heliovaara M, Raitakari O, Lehtimaki T, Eriksson JG, Perola M, Lohmueller KE, Matikainen N, Taskinen MR, Rodriguez-Torres M, Riba L, Tusie-Luna T, Aguilar-Salinas CA, Pajukanta P
Publisher: NATURE PUBLISHING GROUP
Publication year: 2014
Journal: Nature Communications
Journal name in source: NATURE COMMUNICATIONS
Journal acronym: NAT COMMUN
Article number: ARTN 3983
Volume: 5
Issue: 3
Number of pages: 12
ISSN: 2041-1723
DOI: https://doi.org/10.1038/ncomms4983
Dyslipidemia and obesity are especially prevalent in populations with Amerindian backgrounds, such as Mexican- Americans, which predispose these populations to cardiovascular disease. Here we design an approach, known as the cross- population allele screen (CPAS), which we conduct prior to a genome- wide association study (GWAS) in 19,273 Europeans and Mexicans, in order to identify Amerindian risk genes in Mexicans. Utilizing CPAS to restrict the GWAS input variants to only those differing in frequency between the two populations, we identify novel Amerindian lipid genes, receptor- related orphan receptor alpha (RORA) and salt- inducible kinase 3 (SIK3), and three loci previously unassociated with dyslipidemia or obesity. We also detect lipoprotein lipase (LPL) and apolipoprotein A5 (APOA5) harbouring specific Amerindian signatures of risk variants and haplotypes. Notably, we observe that SIK3 and one novel lipid locus underwent positive selection in Mexicans. Furthermore, after a high- fat meal, the SIK3 risk variant carriers display high triglyceride levels. These findings suggest that Amerindian- specific genetic architecture leads to a higher incidence of dyslipidemia and obesity in modern Mexicans.
