Genome-wide association studies of 27 accelerometry-derived physical activity measurements identified novel loci and genetic mechanisms.
Genome-wide association studies of 27 accelerometry-derived physical activity measurements identified novel loci and genetic mechanisms.
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DOI：
10.1002/gepi.22441
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发表时间：
2022-03
影响因子：
2.1
通讯作者：
Chatterjee N
中科院分区：
文献类型：
--
作者：
Qi G;Dutta D;Leroux A;Ray D;Muschelli J;Crainiceanu C;Chatterjee N
缺乏身体活动（PA）是许多疾病的重要危险因素。先前的全基因组关联研究（GWAS）基于自我报告的数据或来自加速度计的少量表型，已经确定了与习惯性PA相关的有限数量的遗传位点，并提供了中枢神经系统参与介导遗传效应的证据。在这项研究中，我们从88,411名英国生物银行研究参与者的手腕加速度测量数据中获得了27种PA表型。基于混合效应模型的单变量关联分析和转录组全关联研究（TWAS）共同确定了5个新的基因座，这些基因座在PA、睡眠时间和自我报告的时型研究中未被发现。对于新的和先前已知的基因座，我们发现了与新表型的关联，包括活动到久坐的转变概率、光强度PA、一天中不同时间的活动以及睡眠和昼夜节律模式的代理表型。后续研究包括TWAS、共定位、组织特异性遗传力富集、基因集富集和遗传相关性分析，表明血液和免疫系统在调节遗传效应中起作用，消化和内分泌系统起次要作用。我们的发现为PA的遗传结构及其潜在机制提供了重要的见解。
Physical inactivity (PA) is an important risk factor for a wide range of diseases. Previous genome-wide association studies (GWAS), based on self-reported data or a small number of phenotypes derived from accelerometry, have identified a limited number of genetic loci associated with habitual PA and provided evidence for involvement of central nervous system in mediating genetic effects. In this study, we derived 27 PA phenotypes from wrist accelerometry data obtained from 88,411 UK Biobank study participants. Single-variant association analysis based on mixed-effects models and transcriptome-wide association studies (TWAS) together identified 5 novel loci that were not detected by previous studies of PA, sleep duration and self-reported chronotype. For both novel and previously known loci, we discovered associations with novel phenotypes including active-to-sedentary transition probability, light-intensity PA, activity during different times of the day and proxy phenotypes to sleep and circadian patterns. Follow-up studies including TWAS, colocalization, tissue-specific heritability enrichment, gene-set enrichment and genetic correlation analyses indicated the role of the blood and immune system in modulating the genetic effects and a secondary role of the digestive and endocrine systems. Our findings provided important insights into the genetic architecture of PA and its underlying mechanisms.
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影响因子：
64.8
作者：
Bycroft C;Freeman C;Petkova D;Band G;Elliott LT;Sharp K;Motyer A;Vukcevic D;Delaneau O;O'Connell J;Cortes A;Welsh S;Young A;Effingham M;McVean G;Leslie S;Allen N;Donnelly P;Marchini J
通讯作者：
Marchini J
遗传对人体组织基因表达的影响。
影响因子：
64.8
作者：
GTEx Consortium;Laboratory, Data Analysis &Coordinating Center (LDACC)—Analysis Working Group;Statistical Methods groups—Analysis Working Group;Enhancing GTEx (eGTEx) groups;NIH Common Fund;NIH/NCI;NIH/NHGRI;NIH/NIMH;NIH/NIDA;Biospecimen Collection Source Site—NDRI;Biospecimen Collection Source Site—RPCI;Biospecimen Core Resource—VARI;Brain Bank Repository—University of Miami Brain Endowment Bank;Leidos Biomedical—Project Management;ELSI Study;Genome Browser Data Integration &Visualization—EBI;Genome Browser Data Integration &Visualization—UCSC Genomics Institute, University of California Santa Cruz;Lead analysts:;Laboratory, Data Analysis &Coordinating Center (LDACC):;NIH program management:;Biospecimen collection:;Pathology:;eQTL manuscript working group:;Battle A;Brown CD;Engelhardt BE;Montgomery SB
通讯作者：
Montgomery SB
DOI：
10.1038/s41366-018-0120-3
发表时间：
2018-06
期刊：
International journal of obesity (2005)
影响因子：
--
作者：
Klimentidis YC;Raichlen DA;Bea J;Garcia DO;Wineinger NE;Mandarino LJ;Alexander GE;Chen Z;Going SB
通讯作者：
Going SB
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.
影响因子：
30.8
作者：
Finucane HK;Bulik-Sullivan B;Gusev A;Trynka G;Reshef Y;Loh PR;Anttila V;Xu H;Zang C;Farh K;Ripke S;Day FR;ReproGen Consortium;Schizophrenia Working Group of the Psychiatric Genomics Consortium;RACI Consortium;Purcell S;Stahl E;Lindstrom S;Perry JR;Okada Y;Raychaudhuri S;Daly MJ;Patterson N;Neale BM;Price AL
通讯作者：
Price AL