Genome-wide association study of habitual physical activity in over 377,000 UK Biobank participants identifies multiple variants including CADM2 and APOE.
Genome-wide association study of habitual physical activity in over 377,000 UK Biobank participants identifies multiple variants including CADM2 and APOE.
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DOI：
10.1038/s41366-018-0120-3
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发表时间：
2018-06
期刊：
影响因子：
--
通讯作者：
Going SB
中科院分区：
文献类型：
--
作者：
Klimentidis YC;Raichlen DA;Bea J;Garcia DO;Wineinger NE;Mandarino LJ;Alexander GE;Chen Z;Going SB
身体活动（PA）可以预防多种疾病。习惯性PA似乎是可遗传的，这促使人们寻找特定的遗传变异，这可能会为促进PA和针对每个人的最佳PA类型的努力提供信息。我们使用来自英国生物银行的数据进行了迄今为止最大的PA全基因组关联研究，使用了基于自我报告的三项测量（nmax= 377，234）和基于腕戴式加速度计数据的两项测量（nmax= 91，084）。我们研究了PA与其他性状和疾病的遗传相关性，以及组织特异性基因表达模式。根据社区动脉粥样硬化风险（ARIC; n= 8，556）研究的数据，我们对中度至剧烈PA（MVPA）的最高命中率进行了荟萃分析。我们在所有PA指标中确定了10个位点，这些位点在基本模型和完全校正模型中均具有显著性（p<5 × 10−9）。根据ARIC结果对MVPA的9个最高命中进行荟萃分析后，8个具有全基因组显著性。有趣的是，其中，APOE基因中的rs 429358变体与MVPA的相关性最强，而与阿尔茨海默病风险较高相关的等位基因与MVPA较高相关。然而，我们不能排除这一结果背后可能存在的选择偏倚。CADM 2是一种先前与肥胖、冒险行为和其他特征有关的基因，其变异体被发现与习惯性PA有关。我们还在自我报告和加速度测量中确定了与PA一致相关（p<5 × 10 - 5）的三个位点，包括CADM 2。我们发现PA与教育程度、时间型、精神病特征和肥胖相关特征的遗传相关性。组织富集分析暗示脑和垂体是PA相关位点发挥作用的位置。这些结果为习惯性PA的遗传基础以及PA与其他性状和疾病的遗传联系提供了新的见解。
Physical activity (PA) protects against a wide range of diseases. Habitual PA appears to be heritable, motivating the search for specific genetic variants that may inform efforts to promote PA and target the best type of PA for each individual. We used data from the UK Biobank to perform the largest genome-wide association study of PA to date, using three measures based on self-report (nmax=377,234) and two measures based on wrist-worn accelerometry data (nmax=91,084). We examined genetic correlations of PA with other traits and diseases, as well as tissue-specific gene expression patterns. With data from the Atherosclerosis Risk in Communities (ARIC; n=8,556) study, we performed a meta-analysis of our top hits for moderate-to-vigorous PA (MVPA). We identified ten loci across all PA measures that were significant in both a basic and a fully adjusted model (p<5 × 10−9). Upon meta-analysis of the nine top hits for MVPA with results from ARIC, eight were genome-wide significant. Interestingly, among these, the rs429358 variant in the APOE gene was the most strongly associated with MVPA, whereby the allele associated with higher Alzheimer’s risk was associated with greater MVPA. However, we were not able to rule out possible selection bias underlying this result. Variants in CADM2, a gene previously implicated in obesity, risk-taking behavior and other traits, were found to be associated with habitual PA. We also identified three loci consistently associated (p<5 × 10−5) with PA across both self-report and accelerometry, including CADM2. We find genetic correlations of PA with educational attainment, chronotype, psychiatric traits, and obesity-related traits. Tissue enrichment analyses implicate the brain and pituitary gland as locations where PA-associated loci may exert their actions. These results provide new insight into the genetic basis of habitual PA, and the genetic links connecting PA with other traits and diseases.
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影响因子：
9.8
作者：
Dudbridge F;Fletcher O
通讯作者：
Fletcher O
来自1,092个人基因组的遗传变异的综合图。
影响因子：
64.8
作者：
通讯作者：
--
影响因子：
30.8
作者：
Bulik-Sullivan, Brendan K.;Loh, Po-Ru;Finucane, Hilary K.;Ripke, Stephan;Yang, Jian;Patterson, Nick;Daly, Mark J.;Price, Alkes L.;Neale, Benjamin M.
通讯作者：
Neale, Benjamin M.
DOI：
10.1126/science.1262110
发表时间：
2015-05-08
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
GTEx Consortium
通讯作者：
GTEx Consortium
影响因子：
30.8
作者：
Bulik-Sullivan B;Finucane HK;Anttila V;Gusev A;Day FR;Loh PR;ReproGen Consortium;Psychiatric Genomics Consortium;Genetic Consortium for Anorexia Nervosa of the Wellcome Trust Case Control Consortium 3;Duncan L;Perry JR;Patterson N;Robinson EB;Daly MJ;Price AL;Neale BM
通讯作者：
Neale BM