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Nat Commun. 2014 Jun 2;5:3983. doi: 10.1038/ncomms4983.

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

Author information

1
1] Department of Human Genetics, David Geffen School of Medicine at UCLA, Los Angeles, California 90095, USA [2] Molecular Biology Institute at UCLA, Los Angeles, California 90095, USA.
2
Department of Human Genetics, David Geffen School of Medicine at UCLA, Los Angeles, California 90095, USA.
3
1] Department of Human Genetics, David Geffen School of Medicine at UCLA, Los Angeles, California 90095, USA [2] Department of Pathology and Laboratory Medicine, David Geffen School of Medicine at UCLA, Los Angeles, California 90095, USA [3] Bioinformatics Interdepartmental Program, UCLA, Los Angeles, California 90095, USA.
4
Bioinformatics Interdepartmental Program, UCLA, Los Angeles, California 90095, USA.
5
1] Instituto Nacional de Ciencias Médicas y Nutrición, Salvador Zubiran, 14000 Mexico City, Mexico [2] Instituto de Investigaciones Biomédicas de la UNAM, 04510 04510 Mexico City, Mexico.
6
Instituto Nacional de Ciencias Médicas y Nutrición, Salvador Zubiran, 14000 Mexico City, Mexico.
7
National Institute for Health and Welfare, 00271 Helsinki, Finland.
8
1] National Institute for Health and Welfare, 00271 Helsinki, Finland [2] Department of Public Health, Hjelt Institute, University of Helsinki, 00014 Helsinki, Finland [3] Institute for Molecular Medicine Finland FIMM, University of Helsinki, 00014 Helsinki, Finland.
9
1] Research Centre of Applied and Preventive Cardiovascular Medicine, University of Turku, 20520 Turku, Finland [2] Department of Clinical Physiology and Nuclear Medicine, Turku University Hospital, 20520 Turku, Finland.
10
Department of Clinical Chemistry, Fimlab Laboratories and University of Tampere School of Medicine, 33100 Tampere, Finland.
11
1] National Institute for Health and Welfare, 00271 Helsinki, Finland [2] Folkhälsan Research Center, University of Helsinki, 00290 Helsinki, Finland [3] Department of General Practice and Primary Health Care, University of Helsinki, 00014 Helsinki, Finland.
12
1] National Institute for Health and Welfare, 00271 Helsinki, Finland [2] Institute for Molecular Medicine Finland FIMM, University of Helsinki, 00014 Helsinki, Finland [3] University of Tartu, Estonian Genome Center, 51010 Tartu, Estonia.
13
Department of Ecology and Evolutionary Biology, UCLA, Los Angeles, California 90095, USA.
14
Department of Medicine, University of Helsinki, 00014 Helsinki, Finland.

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.

PMID:
24886709
PMCID:
PMC4062071
DOI:
10.1038/ncomms4983
[Indexed for MEDLINE]
Free PMC Article

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