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


ABSTRACT: 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.

SUBMITTER: Ko A 

PROVIDER: S-EPMC4062071 | biostudies-literature | 2014 Jun

REPOSITORIES: biostudies-literature

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

Ko Arthur A   Cantor Rita M RM   Weissglas-Volkov Daphna D   Nikkola Elina E   Reddy Prasad M V Linga PM   Sinsheimer Janet S JS   Pasaniuc Bogdan B   Brown Robert R   Alvarez Marcus M   Rodriguez Alejandra A   Rodriguez-Guillen Rosario R   Bautista Ivette C IC   Arellano-Campos Olimpia O   Muñoz-Hernández Linda L LL   Salomaa Veikko V   Kaprio Jaakko J   Jula Antti A   Jauhiainen Matti M   Heliövaara Markku M   Raitakari Olli O   Lehtimäki Terho T   Eriksson Johan G JG   Perola Markus M   Lohmueller Kirk E KE   Matikainen Niina N   Taskinen Marja-Riitta MR   Rodriguez-Torres Maribel M   Riba Laura L   Tusie-Luna Teresa T   Aguilar-Salinas Carlos A CA   Pajukanta Päivi P  

Nature communications 20140602


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 freq  ...[more]

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