A multi-level gene-diet interaction analysis of fish oil and 14 polyunsaturated fatty acid traits identifies the FADS and GRP12 loci.

IF 3.3 Q2 GENETICS & HEREDITY
Susan Adanna Ihejirika, Alexandra Huong Chiang, Aryaman Singh, Eunice Stephen, Han Chen, Kaixiong Ye
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Abstract

Fish oil supplements (FOS) are known to alter circulating levels of polyunsaturated fatty acids (PUFAs) but in a heterogeneous manner across individuals. These varied responses may result from unidentified gene-FOS interactions. To identify genetic factors that interact with FOS to alter the circulating levels of PUFAs, we performed a multi-level genome-wide interaction study (GWIS) of FOS on 14 plasma measurements in 200,060 unrelated European-ancestry individuals from the UK Biobank. From our single-variant tests, we identified genome-wide significant interacting SNPs (P < 5 × 10-8) in the FADS1-FADS2 gene cluster for total omega-3, omega-3%, docosapentaenoic acid (DHA), DHA% and the omega-6 to omega-3 ratio. Among the interaction signals for omega-3%, the lead SNP, rs35473591 (C>CT, CT allele frequency = 0.34), had a lower association effect size in the FOS-taking group (β = 0.35 for allele C) than that in the group without FOS (β = 0.42). Likewise, the effect sizes of associations between FOS and omega-3% varied across the three genotype groups (β = 0.45, 0.50, and 0.59, respectively, in C/C, C/CT, and CT/CT). Our gene-level aggregate and transcriptome-wide interaction analyses identified significant signals at two loci, around FADS1-FADS2 and GRP12. The contribution of genome-wide gene-FOS interactions to phenotypic variance was statistically significant in omega-3-related traits. This systemic gene-FOS GWIS contributes to our understanding of the genetic architecture of circulating PUFAs underlying FOS response and informs personalized dietary recommendations.

通过对鱼油和14个多不饱和脂肪酸性状的多层次基因-饲料互作分析,确定了FADS和GRP12位点。
众所周知,鱼油补充剂(FOS)可以改变多不饱和脂肪酸(PUFAs)的循环水平,但在个体之间存在异质性。这些不同的反应可能是未知基因- fos相互作用的结果。为了确定与FOS相互作用以改变PUFAs循环水平的遗传因素,我们对来自英国生物银行的200,060名无血缘关系的欧洲血统个体进行了14项血浆测量,对FOS进行了多层次全基因组相互作用研究(GWIS)。从我们的单变量测试中,我们在FADS1-FADS2基因簇中发现了全基因组范围内显著的相互作用snp (P < 5 × 10-8),涉及总omega-3、omega-3%、二十二碳五烯酸(DHA)、DHA%和omega-6与omega-3的比例。在omega-3%的相互作用信号中,服用FOS组的先导SNP rs35473591 (C>CT, CT等位基因频率= 0.34)的关联效应大小(等位基因C的β = 0.35)低于未服用FOS组(β = 0.42)。同样,在三个基因型组中,FOS和omega-3%之间的关联效应大小也各不相同(β在C/C、C/CT和CT/CT中分别= 0.45、0.50和0.59)。我们的基因水平聚合和转录组互作分析在FADS1-FADS2和GRP12周围的两个位点上发现了显著的信号。在omega-3相关性状中,全基因组基因- fos相互作用对表型变异的贡献具有统计学意义。这种系统性基因-FOS GWIS有助于我们了解循环PUFAs在FOS反应中的遗传结构,并为个性化饮食建议提供信息。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
HGG Advances
HGG Advances Biochemistry, Genetics and Molecular Biology-Molecular Medicine
CiteScore
4.30
自引率
4.50%
发文量
69
审稿时长
14 weeks
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