Large-Scale Analyses Provide No Evidence for Gene-Gene Interactions Influencing Type 2 Diabetes Risk.
Large-Scale Analyses Provide No Evidence for Gene-Gene Interactions Influencing Type 2 Diabetes Risk.
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作者：
Nag A;McCarthy MI;Mahajan A
越来越多的遗传位点已被证明会影响2型糖尿病（T2 D）的个体易感性。尽管长期以来对了解这些风险变体之间的非线性相互作用是否会额外影响T2 D风险感兴趣，但迄今为止检测显著基因-基因相互作用（GGI）效应的能力有限。为了提高检测GGI效应的能力，我们将因果性T2 D风险变异的精细映射的最新进展与英国生物库中增加的样本量（375，736名无关的欧洲参与者，包括16，430名T2 D参与者）相结合。除了传统的基于单变量的分析外，我们还使用了一种互补的基于多基因评分的方法，其中包括分区的T2 D风险评分，该评分捕获了与T2 D病理生理学相关的生物学过程。然而，我们没有发现支持GGI影响T2 D风险的证据。目前的研究有能力检测比值比>1.2的常见变异之间的相互作用，因此这些发现限制了GGIs对T2 D整体遗传力的贡献。
A growing number of genetic loci have been shown to influence individual predisposition to type 2 diabetes (T2D). Despite longstanding interest in understanding whether nonlinear interactions between these risk variants additionally influence T2D risk, the ability to detect significant gene-gene interaction (GGI) effects has been limited to date. To increase power to detect GGI effects, we combined recent advances in the fine-mapping of causal T2D risk variants with the increased sample size available within UK Biobank (375,736 unrelated European participants, including 16,430 with T2D). In addition to conventional single variant–based analysis, we used a complementary polygenic score–based approach, which included partitioned T2D risk scores that capture biological processes relevant to T2D pathophysiology. Nevertheless, we found no evidence in support of GGI effects influencing T2D risk. The current study was powered to detect interactions between common variants with odds ratios >1.2, so these findings place limits on the contribution of GGIs to the overall heritability of T2D.
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影响因子：
4.6
作者：
Wei WH;Bowes J;Plant D;Viatte S;Yarwood A;Massey J;Worthington J;Eyre S
通讯作者：
Eyre S
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
影响因子：
30.8
作者：
Mahajan A;Taliun D;Thurner M;Robertson NR;Torres JM;Rayner NW;Payne AJ;Steinthorsdottir V;Scott RA;Grarup N;Cook JP;Schmidt EM;Wuttke M;Sarnowski C;Mägi R;Nano J;Gieger C;Trompet S;Lecoeur C;Preuss MH;Prins BP;Guo X;Bielak LF;Below JE;Bowden DW;Chambers JC;Kim YJ;Ng MCY;Petty LE;Sim X;Zhang W;Bennett AJ;Bork-Jensen J;Brummett CM;Canouil M;Ec Kardt KU;Fischer K;Kardia SLR;Kronenberg F;Läll K;Liu CT;Locke AE;Luan J;Ntalla I;Nylander V;Schönherr S;Schurmann C;Yengo L;Bottinger EP;Brandslund I;Christensen C;Dedoussis G;Florez JC;Ford I;Franco OH;Frayling TM;Giedraitis V;Hackinger S;Hattersley AT;Herder C;Ikram MA;Ingelsson M;Jørgensen ME;Jørgensen T;Kriebel J;Kuusisto J;Ligthart S;Lindgren CM;Linneberg A;Lyssenko V;Mamakou V;Meitinger T;Mohlke KL;Morris AD;Nadkarni G;Pankow JS;Peters A;Sattar N;Stančáková A;Strauch K;Taylor KD;Thorand B;Thorleifsson G;Thorsteinsdottir U;Tuomilehto J;Witte DR;Dupuis J;Peyser PA;Zeggini E;Loos RJF;Froguel P;Ingelsson E;Lind L;Groop L;Laakso M;Collins FS;Jukema JW;Palmer CNA;Grallert H;Metspalu A;Dehghan A;Köttgen A;Abecasis GR;Meigs JB;Rotter JI;Marchini J;Pedersen O;Hansen T;Langenberg C;Wareham NJ;Stefansson K;Gloyn AL;Morris AP;Boehnke M;McCarthy MI
通讯作者：
McCarthy MI
影响因子：
14.9
作者：
Buniello, Annalisa;MacArthur, Jacqueline A. L.;Parkinson, Helen
通讯作者：
Parkinson, Helen
影响因子：
7.7
作者：
Wong, MY;Day, NE;Wareham, NJ
通讯作者：
Wareham, NJ