Exploring the genetic architecture of inflammatory bowel disease by whole genome sequencing identifies association at ADCY7
Exploring the genetic architecture of inflammatory bowel disease by whole genome sequencing identifies association at ADCY7
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通过全基因组测序探索炎症性肠病的遗传结构，确定 ADCY7 的关联
DOI：
10.1101/058347
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发表时间：
2016
期刊：
影响因子：
--
通讯作者：
Luo Y
中科院分区：
文献类型：
--
作者：
Luo Y
为了进一步解决炎症性肠病溃疡性结肠炎和克罗恩病的遗传结构，我们对低覆盖率的4280例患者的全基因组进行了测序，并将其与先前测序的3,652例人群对照进行了比较，这些对照涉及7350万个变体。然后，我们将这些序列输入到新的和现有的全基因组关联研究队列中，并在总共16,432例病例和18,843例对照中测试了约1200万个变体的相关性。我们发现adcy7中0.6%的频率错义变异使溃疡性结肠炎的风险增加了一倍。尽管有良好的统计能力，但我们没有发现任何其他新的低频风险变异，并且发现这些变异几乎不能解释遗传性。我们在已知的克罗恩病风险基因中发现了非常罕见的、破坏性的错义变异，这表明更全面的测序研究将继续提高对复杂疾病生物学的理解。
To further resolve the genetic architecture of the inflammatory bowel diseases ulcerative colitis and Crohn's disease, we sequenced the whole genomes of 4,280 patients at low coverage and compared them to 3,652 previously sequenced population controls across 73.5 million variants. We then imputed from these sequences into new and existing genome-wide association study cohorts and tested for association at ∼12 million variants in a total of 16,432 cases and 18,843 controls. We discovered a 0.6% frequency missense variant inADCY7that doubles the risk of ulcerative colitis. Despite good statistical power, we did not identify any other new low-frequency risk variants and found that such variants explained little heritability. We detected a burden of very rare, damaging missense variants in known Crohn's disease risk genes, suggesting that more comprehensive sequencing studies will continue to improve understanding of the biology of complex diseases.
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影响因子：
4.5
作者：
Prescott NJ;Lehne B;Stone K;Lee JC;Taylor K;Knight J;Papouli E;Mirza MM;Simpson MA;Spain SL;Lu G;Fraternali F;Bumpstead SJ;Gray E;Amar A;Bye H;Green P;Chung-Faye G;Hayee B;Pollok R;Satsangi J;Parkes M;Barrett JC;Mansfield JC;Sanderson J;Lewis CM;Weale ME;Schlitt T;Mathew CG;UK IBD Genetics Consortium
通讯作者：
UK IBD Genetics Consortium
影响因子：
30.8
作者：
Ellinghaus D;Jostins L;Spain SL;Cortes A;Bethune J;Han B;Park YR;Raychaudhuri S;Pouget JG;Hübenthal M;Folseraas T;Wang Y;Esko T;Metspalu A;Westra HJ;Franke L;Pers TH;Weersma RK;Collij V;D'Amato M;Halfvarson J;Jensen AB;Lieb W;Degenhardt F;Forstner AJ;Hofmann A;International IBD Genetics Consortium (IIBDGC);International Genetics of Ankylosing Spondylitis Consortium (IGAS);International PSC Study Group (IPSCSG);Genetic Analysis of Psoriasis Consortium (GAPC);Psoriasis Association Genetics Extension (PAGE);Schreiber S;Mrowietz U;Juran BD;Lazaridis KN;Brunak S;Dale AM;Trembath RC;Weidinger S;Weichenthal M;Ellinghaus E;Elder JT;Barker JN;Andreassen OA;McGovern DP;Karlsen TH;Barrett JC;Parkes M;Brown MA;Franke A
通讯作者：
Franke A
DOI：
10.1093/bioinformatics/bts180
发表时间：
2012-06-15
期刊：
Bioinformatics (Oxford, England)
影响因子：
--
作者：
Shah TS;Liu JZ;Floyd JA;Morris JA;Wirth N;Barrett JC;Anderson CA
通讯作者：
Anderson CA
影响因子：
9.8
作者：
Browning, Brian L.;Browning, Sharon R.
通讯作者：
Browning, Sharon R.
影响因子：
3.5
作者：
Chen, Guo-Bo;Lee, Sang Hong;Visscher, Peter M.
通讯作者：
Visscher, Peter M.