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

ABSTRACT: OBJECTIVES:To 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). METHODS:A 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 (?(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. RESULTS:We 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. CONCLUSIONS:We 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.

SUBMITTER: Aslibekyan S 

PROVIDER: S-EPMC3785243 | biostudies-literature | 2013 Sep-Oct

REPOSITORIES: biostudies-literature