Department of Epidemiology, University of Alabama at Birmingham, Birmingham, Alabama, 35294.
Am J Hum Biol. 2013 Sep-Oct;25(5):673-80. doi: 10.1002/ajhb.22429. Epub 2013 Aug 1.
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).
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 (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.
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.
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.
在尤皮克人群中鉴定与空腹血脂谱、胰岛素、葡萄糖和糖化血红蛋白相关的基因组区域，并评估遗传因素与代谢特征之间的观察到的关联是否受海洋衍生ω-3 多不饱和脂肪酸（n-3PUFA）饮食摄入的影响。
在阿拉斯加原住民健康研究中心的 982 名参与者中进行了全基因组连锁扫描。n-3PUFA 的摄入量是通过红细胞的氮稳定同位素比值（δ（15）N）来估计的。所有位于 LOD 得分>2 的基因组区域内的基因分型 SNP 随后使用线性模型进行个体 SNP 与代谢特征的关联测试，该模型考虑了家族相关性以及年龄、性别、社区群体和 n-3PUFA 的摄入量。分别建立线性模型来评估感兴趣的基因型与 n-3PUFA 摄入量之间的相互作用。
我们鉴定了几个与血清载脂蛋白 A2、高密度脂蛋白、低密度脂蛋白和总胆固醇、胰岛素和糖化血红蛋白相关的染色体区域。与总胆固醇相关的遗传变异映射到包含染色体 19 上先前验证的脂质基因座的区域，并且在 11q12.2-11q13.2 处鉴定到了其他具有生物学意义的新峰。我们没有观察到 n-3PUFA 摄入、基因型和代谢特征之间的任何显著相互作用。
我们已经完成了对原住民代谢特征的全基因组连锁扫描，确认了先前确定的基因座，并为该人群中慢性疾病发病机制涉及的新基因座提供了初步证据。
