Genome-wide analysis of 53,400 people with irritable bowel syndrome highlights shared genetic pathways with mood and anxiety disorders.
Genome-wide analysis of 53,400 people with irritable bowel syndrome highlights shared genetic pathways with mood and anxiety disorders.
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DOI：
10.1038/s41588-021-00950-8
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发表时间：
2021-11
期刊：
影响因子：
30.8
通讯作者：
Parkes M
中科院分区：
文献类型：
--
作者：
Eijsbouts C;Zheng T;Kennedy NA;Bonfiglio F;Anderson CA;Moutsianas L;Holliday J;Shi J;Shringarpure S;23andMe Research Team;Voda AI;Bellygenes Initiative;Farrugia G;Franke A;Hübenthal M;Abecasis G;Zawistowski M;Skogholt AH;Ness-Jensen E;Hveem K;Esko T;Teder-Laving M;Zhernakova A;Camilleri M;Boeckxstaens G;Whorwell PJ;Spiller R;McVean G;D'Amato M;Jostins L;Parkes M
肠易激综合征（IBS）是脑-肠相互作用紊乱的结果。确定易感基因可以突出潜在的病理生理机制。我们为英国生物银行设计了一份消化系统健康问卷，并将确定的IBS病例与独立队列相结合。我们对53,400例病例和433,201例对照进行了全基因组关联研究，并在23andMe小组（205,252例病例和1,384,055例对照）中重复了显著关联。我们的研究确定并确认了肠易激综合征的6个遗传易感位点。涉及的基因包括NCAM1、CADM2、PHF2/FAM120A、DOCK9、CKAP2/TPTE2P3和BAG6。前四种与情绪和焦虑障碍有关，表现在神经系统中，或两者兼而有之。与此相呼应的是，我们还发现肠易激综合征的风险与焦虑、神经质和抑郁之间存在很强的全基因组相关性（rg>.5）。其他分析表明，这是由于共同的致病途径，而不是例如焦虑引起的腹部症状。涉及的机制需要进一步探索，以帮助理解肠易激综合征背后改变的脑-肠相互作用。肠易激综合征的全基因组关联分析确定了遗传易感性位点，并强调了与情绪和焦虑障碍的共享途径。
Irritable bowel syndrome (IBS) results from disordered brain–gut interactions. Identifying susceptibility genes could highlight the underlying pathophysiological mechanisms. We designed a digestive health questionnaire for UK Biobank and combined identified cases with IBS with independent cohorts. We conducted a genome-wide association study with 53,400 cases and 433,201 controls and replicated significant associations in a 23andMe panel (205,252 cases and 1,384,055 controls). Our study identified and confirmed six genetic susceptibility loci for IBS. Implicated genes included NCAM1, CADM2, PHF2/FAM120A, DOCK9, CKAP2/TPTE2P3 and BAG6. The first four are associated with mood and anxiety disorders, expressed in the nervous system, or both. Mirroring this, we also found strong genome-wide correlation between the risk of IBS and anxiety, neuroticism and depression (rg > 0.5). Additional analyses suggested this arises due to shared pathogenic pathways rather than, for example, anxiety causing abdominal symptoms. Implicated mechanisms require further exploration to help understand the altered brain–gut interactions underlying IBS. Genome-wide association analysis of irritable bowel syndrome identifies genetic susceptibility loci and highlights shared pathways with mood and anxiety disorders.
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影响因子：
64.8
作者：
Iossifov, Ivan;O'Roak, Brian J.;Sanders, Stephan J.;Ronemus, Michael;Krumm, Niklas;Levy, Dan;Stessman, Holly A.;Witherspoon, Kali T.;Vives, Laura;Patterson, Karynne E.;Smith, Joshua D.;Paeper, Bryan;Nickerson, Deborah A.;Dea, Jeanselle;Dong, Shan;Gonzalez, Luis E.;Mandell, Jeffrey D.;Mane, Shrikant M.;Murtha, Michael T.;Sullivan, Catherine A.;Walker, Michael F.;Waqar, Zainulabedin;Wei, Liping;Willsey, A. Jeremy;Yamrom, Boris;Lee, Yoon-ha;Grabowska, Ewa;Dalkic, Ertugrul;Wang, Zihua;Marks, Steven;Andrews, Peter;Leotta, Anthony;Kendall, Jude;Hakker, Inessa;Rosenbaum, Julie;Ma, Beicong;Rodgers, Linda;Troge, Jennifer;Narzisi, Giuseppe;Yoon, Seungtai;Schatz, Michael C.;Ye, Kenny;McCombie, W. Richard;Shendure, Jay;Eichler, Evan E.;State, Matthew W.;Wigler, Michael
通讯作者：
Wigler, Michael
影响因子：
29.4
作者：
Camilleri M;Carlson P;Zinsmeister AR;McKinzie S;Busciglio I;Burton D;Zucchelli M;D'Amato M
通讯作者：
D'Amato M
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;Reshef YA;Anttila V;Slowikowski K;Gusev A;Byrnes A;Gazal S;Loh PR;Lareau C;Shoresh N;Genovese G;Saunders A;Macosko E;Pollack S;Brainstorm Consortium;Perry JRB;Buenrostro JD;Bernstein BE;Raychaudhuri S;McCarroll S;Neale BM;Price AL
通讯作者：
Price AL
影响因子：
29.4
作者：
Bonfiglio F;Zheng T;Garcia-Etxebarria K;Hadizadeh F;Bujanda L;Bresso F;Agreus L;Andreasson A;Dlugosz A;Lindberg G;Schmidt PT;Karling P;Ohlsson B;Simren M;Walter S;Nardone G;Cuomo R;Usai-Satta P;Galeazzi F;Neri M;Portincasa P;Bellini M;Barbara G;Latiano A;Hübenthal M;Thijs V;Netea MG;Jonkers D;Chang L;Mayer EA;Wouters MM;Boeckxstaens G;Camilleri M;Franke A;Zhernakova A;D'Amato M
通讯作者：
D'Amato M