TY - JOUR
T1 - Evidence for novel genetic loci associated with metabolic traits in Yup'ik people
AU - Aslibekyan, Stella
AU - Vaughan, Laura Kelly
AU - Wiener, Howard W.
AU - Lemas, Dominick J.
AU - Klimentidis, Yann C.
AU - Havel, Peter J.
AU - Stanhope, Kimber L.
AU - O'brien, Diane M.
AU - Hopkins, Scarlett E.
AU - Boyer, Bert B.
AU - Tiwari, Hemant K.
PY - 2013/9
Y1 - 2013/9
N2 - 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 (δ15N) 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.
AB - 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 (δ15N) 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.
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U2 - 10.1002/ajhb.22429
DO - 10.1002/ajhb.22429
M3 - Article
C2 - 23907821
AN - SCOPUS:84883053326
SN - 1042-0533
VL - 25
SP - 673
EP - 680
JO - American Journal of Human Biology
JF - American Journal of Human Biology
IS - 5
ER -