Genome-wide assessment reveals a significant association between ACSS3 and physical activity

IF 2.4 4区心理学 Q2 BEHAVIORAL SCIENCES

Genes Brain and Behavior Pub Date : 2022-12-12 DOI:10.1111/gbb.12834

Jinyeon Jo, Youngkyu Song, Dankyu Yoon, Chung Gun Lee, Sungho Won

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Abstract

Recent genetic studies have identified physical activity (PA)-susceptible loci in European ancestry subjects; however, due to considerable genetic differences, these findings are not likely extendable to East Asian populations. Therefore, the present study aimed to identify significantly associated PA-susceptible loci using genome-wide association studies (GWASs) with East Asian (EAS) subjects and to generalize the findings to European (EUR) ancestries. The mRNA levels of genes located near the genome-wide significantly associated single-nucleotide polymorphisms (SNP) were compared under PA and control conditions. Rs74937256, located in ACSS3 (chromosome 12), which primarily functions in skeletal muscle tissues, was identified as a genome-wide significant variant (P = 6.06 × 10⁻⁹) in EAS. Additionally, the rs2525840, also in ACSS3 satisfied the Bonferroni corrected significance (P = 3.77 × 10⁻⁵) in EUR. We found that rs74937256 is an expressed trait locus of ACSS3 (P = 10⁻⁴), and ACSS3 mRNA expression significantly differs after PA, based on PrediXcan (P = 7 × 10⁻⁸) and the gene expression omnibus database (P = 0.043).

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全基因组评估揭示了ACSS3与身体活动之间的显著关联

最近的遗传学研究已经确定了欧洲血统受试者的身体活动(PA)易感位点;然而，由于相当大的遗传差异，这些发现不太可能推广到东亚人群。因此，本研究旨在通过东亚(EAS)受试者的全基因组关联研究(GWASs)来确定显著相关的pa易感位点，并将研究结果推广到欧洲(EUR)祖先。在PA和对照条件下，比较了全基因组显著相关单核苷酸多态性(SNP)附近基因的mRNA水平。Rs74937256位于ACSS3(12号染色体)，主要在骨骼肌组织中起作用，在EAS中被鉴定为全基因组显著变异(P = 6.06 × 10−9)。此外，同样在ACSS3中的rs2525840在EUR中满足Bonferroni校正显著性(P = 3.77 × 10−5)。我们发现rs74937256是ACSS3的表达性状位点(P = 10−4)，基于PrediXcan (P = 7 × 10−8)和基因表达综合数据库(P = 0.043)， PA后ACSS3 mRNA表达显著差异。

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来源期刊

Genes Brain and Behavior 医学-行为科学

CiteScore

6.80

自引率

4.00%

发文量

审稿时长

4-8 weeks

期刊介绍： Genes, Brain and Behavior was launched in 2002 with the aim of publishing top quality research in behavioral and neural genetics in their broadest sense. The emphasis is on the analysis of the behavioral and neural phenotypes under consideration, the unifying theme being the genetic approach as a tool to increase our understanding of these phenotypes. Genes Brain and Behavior is pleased to offer the following features: 8 issues per year online submissions with first editorial decisions within 3-4 weeks and fast publication at Wiley-Blackwells High visibility through its coverage by PubMed/Medline, Current Contents and other major abstracting and indexing services Inclusion in the Wiley-Blackwell consortial license, extending readership to thousands of international libraries and institutions A large and varied editorial board comprising of international specialists.