Genome-wide association meta-analysis yields 20 loci associated with gallstone disease.
Genome-wide association meta-analysis yields 20 loci associated with gallstone disease.
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全基因组关联荟萃分析产生了20个与胆结石疾病相关的基因座。
DOI：
10.1038/s41467-018-07460-y
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发表时间：
2018-11-30
影响因子：
16.6
通讯作者：
Stefansson K
中科院分区：
文献类型：
--
作者：
Ferkingstad E;Oddsson A;Gretarsdottir S;Benonisdottir S;Thorleifsson G;Deaton AM;Jonsson S;Stefansson OA;Norddahl GL;Zink F;Arnadottir GA;Gunnarsson B;Halldorsson GH;Helgadottir A;Jensson BO;Kristjansson RP;Sveinbjornsson G;Sverrisson DA;Masson G;Olafsson I;Eyjolfsson GI;Sigurdardottir O;Holm H;Jonsdottir I;Olafsson S;Steingrimsdottir T;Rafnar T;Bjornsson ES;Thorsteinsdottir U;Gudbjartsson DF;Sulem P;Stefansson K
胆结石是西方世界最常见的疾病之一，通常用胆囊切除术治疗。我们对冰岛和英国的两项胆石病全基因组关联研究进行了荟萃分析，共27，174例病例和736，838例对照，在20个位点发现了21种新的胆石相关变异。SLC 10A 2中两种不同的低频错义变体，编码顶端钠依赖性胆汁酸转运蛋白（ASBT），与胆石病风险增加相关（Pro290Ser：OR = 1.36 [1.25-1.49]，P = 2.1 × 10-12，MAF = 1%; Val98Ile：OR = 1.15 [1.10-1.20]，P = 1.8 × 10-10，MAF = 4%）。我们证明ASBT降低胆汁酸转运伴随着更大的胆石病风险，并强调了胆汁酸肠肝循环的肠腔在胆石病易感性中的作用。此外，SERPINA 1和HNF 4A中的两种低频错义变体和17种常见变体代表了与胆石病的新关联。迄今为止，全基因组关联研究已经确定了胆结石疾病的八个风险位点。在这里，作者对来自冰岛和英国的队列进行了荟萃分析，揭示了另外21种常见和低频率的风险变异，这些变异突出了胆汁酸稳态在胆结石疾病中的作用。
Gallstones are responsible for one of the most common diseases in the Western world and are commonly treated with cholecystectomy. We perform a meta-analysis of two genome-wide association studies of gallstone disease in Iceland and the UK, totaling 27,174 cases and 736,838 controls, uncovering 21 novel gallstone-associated variants at 20 loci. Two distinct low frequency missense variants in SLC10A2, encoding the apical sodium-dependent bile acid transporter (ASBT), associate with an increased risk of gallstone disease (Pro290Ser: OR = 1.36 [1.25–1.49], P = 2.1 × 10–12, MAF = 1%; Val98Ile: OR = 1.15 [1.10–1.20], P = 1.8 × 10–10, MAF = 4%). We demonstrate that lower bile acid transport by ASBT is accompanied by greater risk of gallstone disease and highlight the role of the intestinal compartment of the enterohepatic circulation of bile acids in gallstone disease susceptibility. Additionally, two low frequency missense variants in SERPINA1 and HNF4A and 17 common variants represent novel associations with gallstone disease. Genome-wide association studies have so far identified eight risk loci for gallstone disease. Here, the authors perform meta-analysis in cohorts from Iceland and the UK which reveals further 21 common and low-frequency risk variants that highlight the role of bile acid homeostasis in gallstone disease.
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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
DOI：
10.1097/meg.0b013e3283477cc9
发表时间：
2011-08-01
影响因子：
2.1
作者：
Banim, Paul J. R.;Luben, Robert N.;Hart, Andrew R.
通讯作者：
Hart, Andrew R.
影响因子：
30.8
作者：
Buch, Stephan;Schafmayer, Clemens;Hampe, Jochen
通讯作者：
Hampe, Jochen
影响因子：
4.3
作者：
Dikkers, Arne;Tietge, Uwe J. F.
通讯作者：
Tietge, Uwe J. F.
影响因子：
15.9
作者：
ADMIRAND, WH;SMALL, DM
通讯作者：
SMALL, DM