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

Arthur Ko, Rita M. Cantor, Daphna Weissglas-Volkov, Elina Nikkola, Prasad M. V. Linga Reddy, Janet S. Sinsheimer, Bogdan Pasaniuc, Robert Brown, Marcus Alvarez, Alejandra Rodriguez, Rosario Rodriguez-Guillen, Ivette C. Bautista, Olimpia Arellano-Campos, Linda L. Muñoz-Hernández, 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 Taskinen, Maribel Rodriguez-Torres, Laura Riba, Teresa Tusie-Luna, Carlos A. Aguilar-Salinas and Päivi Pajukanta ()
Additional contact information
Arthur Ko: David Geffen School of Medicine at UCLA
Rita M. Cantor: David Geffen School of Medicine at UCLA
Daphna Weissglas-Volkov: David Geffen School of Medicine at UCLA
Elina Nikkola: David Geffen School of Medicine at UCLA
Prasad M. V. Linga Reddy: David Geffen School of Medicine at UCLA
Janet S. Sinsheimer: David Geffen School of Medicine at UCLA
Bogdan Pasaniuc: David Geffen School of Medicine at UCLA
Robert Brown: UCLA
Marcus Alvarez: David Geffen School of Medicine at UCLA
Alejandra Rodriguez: David Geffen School of Medicine at UCLA
Rosario Rodriguez-Guillen: Instituto Nacional de Ciencias Médicas y Nutrición, Salvador Zubiran
Ivette C. Bautista: Instituto Nacional de Ciencias Médicas y Nutrición, Salvador Zubiran
Olimpia Arellano-Campos: Instituto Nacional de Ciencias Médicas y Nutrición, Salvador Zubiran
Linda L. Muñoz-Hernández: Instituto Nacional de Ciencias Médicas y Nutrición, Salvador Zubiran
Veikko Salomaa: National Institute for Health and Welfare
Jaakko Kaprio: National Institute for Health and Welfare
Antti Jula: National Institute for Health and Welfare
Matti Jauhiainen: National Institute for Health and Welfare
Markku Heliövaara: National Institute for Health and Welfare
Olli Raitakari: Research Centre of Applied and Preventive Cardiovascular Medicine, University of Turku
Terho Lehtimäki: Fimlab Laboratories and University of Tampere School of Medicine
Johan G. Eriksson: National Institute for Health and Welfare
Markus Perola: National Institute for Health and Welfare
Kirk E. Lohmueller: UCLA
Niina Matikainen: University of Helsinki
Marja-Riitta Taskinen: University of Helsinki
Maribel Rodriguez-Torres: Instituto Nacional de Ciencias Médicas y Nutrición, Salvador Zubiran
Laura Riba: Instituto Nacional de Ciencias Médicas y Nutrición, Salvador Zubiran
Teresa Tusie-Luna: Instituto Nacional de Ciencias Médicas y Nutrición, Salvador Zubiran
Carlos A. Aguilar-Salinas: Instituto Nacional de Ciencias Médicas y Nutrición, Salvador Zubiran
Päivi Pajukanta: David Geffen School of Medicine at UCLA

Nature Communications, 2014, vol. 5, issue 1, 1-12

Abstract: 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.

Date: 2014
References: Add references at CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/ncomms4983 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:5:y:2014:i:1:d:10.1038_ncomms4983

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/ncomms4983

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().