Evidence for novel genetic loci associated with metabolic traits in Yup'ik people.

• Main Authors: Aslibekyan, Stella, Vaughan, Laura Kelly, Wiener, Howard W, Lemas, Dominick J, Klimentidis, Yann C, Havel, Peter J, Stanhope, Kimber L, O'brien, Diane M, Hopkins, Scarlett E, Boyer, Bert B, Tiwari, Hemant K
• Format: Article in Journal/Newspaper
• Language: unknown
• Published: eScholarship, University of California 2013
• Subjects: Humans; Nitrogen Isotopes; Fatty Acids; Omega-3; Unsaturated; Blood Chemical Analysis; Linear Models; Polymorphism; Single Nucleotide; Adult; Alaska; Female; Male; Genome-Wide Association Study; Genetic Linkage; Evolutionary Biology; Anthropology; Nutrition and Dietetics; Yup'ik
• Online Access: https://escholarship.org/uc/item/8vt3n344

ObjectivesTo identify genomic regions associated with fasting plasma lipid profiles, insulin, glucose, and glycosylated hemoglobin in a Yup'ik study population, and to evaluate whether the observed associations between genetic factors and metabolic traits were modified by dietary intake of marine derived omega-3 polyunsaturated acids (n-3 PUFA).MethodsA genome-wide linkage scan was conducted among 982 participants of the Center for Alaska Native Health Research study. n-3 PUFA intake was estimated using the nitrogen stable isotope ratio (δ(15) N) of erythrocytes. All genotyped SNPs located within genomic regions with LOD scores > 2 were subsequently tested for individual SNP associations with metabolic traits using linear models that account for familial correlation as well as age, sex, community group, and n-3 PUFA intake. Separate linear models were fit to evaluate interactions between the genotype of interest and n-3 PUFA intake.ResultsWe identified several chromosomal regions linked to serum apolipoprotein A2, high density lipoprotein-, low density lipoprotein-, and total cholesterol, insulin, and glycosylated hemoglobin. Genetic variants found to be associated with total cholesterol mapped to a region containing previously validated lipid loci on chromosome 19, and additional novel peaks of biological interest were identified at 11q12.2-11q13.2. We did not observe any significant interactions between n-3 PUFA intake, genotypes, and metabolic traits.ConclusionsWe have completed a whole genome linkage scan for metabolic traits in Native Alaskans, confirming previously identified loci, and offering preliminary evidence of novel loci implicated in chronic disease pathogenesis in this population.