학술논문

Evidence for novel genetic loci associated with metabolic traits in Yup'ik people
Document Type
article
Source
American Journal of Human Biology. 25(5)
Subject
Biomedical and Clinical Sciences
Nutrition and Dietetics
Clinical Research
Human Genome
Genetics
Nutrition
American Indian or Alaska Native
Prevention
Aetiology
2.1 Biological and endogenous factors
Metabolic and endocrine
Adult
Alaska
Blood Chemical Analysis
Fatty Acids
Omega-3
Fatty Acids
Unsaturated
Female
Genetic Linkage
Genome-Wide Association Study
Humans
Linear Models
Male
Nitrogen Isotopes
Polymorphism
Single Nucleotide
Evolutionary Biology
Anthropology
Nutrition and dietetics
Language
Abstract
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.