Amerindian-specific regions under positive selection harbour new lipid variants in Latinos
| Autor: | Päivi Pajukanta, Niina Matikainen, Alejandra Rodriguez, Carlos A. Aguilar-Salinas, Johan G. Eriksson, Laura Riba, Marja-Riitta Taskinen, Matti Jauhiainen, Daphna Weissglas-Volkov, Olli T. Raitakari, Veikko Salomaa, Ivette Cruz Bautista, Rosario Rodríguez-Guillén, Janet S. Sinsheimer, Maribel Rodríguez-Torres, Robert Brown, Antti Jula, Rita M. Cantor, Marcus Alvarez, Elina Nikkola, Terho Lehtimäki, Markus Perola, Bogdan Pasaniuc, Prasad M. V. Linga Reddy, Olimpia Arellano-Campos, Teresa Tusie-Luna, Jaakko Kaprio, Kirk E. Lohmueller, Arthur Ko, Linda L. Muñoz-Hernández, Markku Heliövaara |
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| Rok vydání: | 2014 |
| Předmět: |
Male
General Physics and Astronomy Genome-wide association study Disease 030204 cardiovascular system & hematology Cardiovascular Bioinformatics 0302 clinical medicine Indians Group F 2.1 Biological and endogenous factors Aetiology Pair 11 Hypertriglyceridemia 2. Zero hunger Genetics 0303 health sciences Multidisciplinary Nuclear Receptor Subfamily 1 Group F Member 1 Single Nucleotide Middle Aged Pair 8 Female North American Chromosomes Human Pair 8 Human Adult Member 1 Genotype Nuclear Receptor Subfamily 1 Hypercholesterolemia European Continental Ancestry Group Locus (genetics) Biology Polymorphism Single Nucleotide White People Article Chromosomes General Biochemistry Genetics and Molecular Biology Young Adult 03 medical and health sciences Clinical Research medicine Humans Genetic Predisposition to Disease Obesity Polymorphism Allele Mexico Apolipoproteins A Nutrition Dyslipidemias 030304 developmental biology Prevention Chromosomes Human Pair 11 Human Genome Haplotype General Chemistry ta3121 Atherosclerosis medicine.disease Genetic architecture Lipoprotein Lipase Logistic Models Haplotypes Apolipoprotein A-V Case-Control Studies Indians North American Protein Kinases Dyslipidemia Genome-Wide Association Study |
| Zdroj: | Nature communications, vol 5, iss 1 Ko, A; Cantor, RM; Weissglas-Volkov, D; Nikkola, E; Reddy, PMVL; Sinsheimer, JS; et al.(2014). Amerindian-specific regions under positive selection harbour new lipid variants in Latinos. Nature Communications, 5. doi: 10.1038/ncomms4983. UCLA: Retrieved from: http://www.escholarship.org/uc/item/5qf115w5 Nature Communications |
| ISSN: | 2041-1723 |
| DOI: | 10.1038/ncomms4983. |
| Popis: | 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. Dyslipidemia and obesity have a high prevalence in populations with Amerindian backgrounds, such as Mexican–Americans. Here, the authors design an approach to identify Amerindian risk genes in Mexicans and identify five genomic loci, which include RORA and SIK3 that may contribute to the risk of dyslipidemia and obesity in Amerindian populations. |
| Databáze: | OpenAIRE |
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