Item-Level Genome-Wide Association Study of the Alcohol Use Disorders Identification Test in Three Population-Based Cohorts.
Item-Level Genome-Wide Association Study of the Alcohol Use Disorders Identification Test in Three Population-Based Cohorts.
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DOI：
10.1176/appi.ajp.2020.20091390
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发表时间：
2022-01
影响因子：
17.7
通讯作者：
Sanchez-Roige, Sandra
中科院分区：
文献类型：
--
作者：
Mallard, Travis T.;Savage, Jeanne E.;Johnson, Emma C.;Huang, Yuye;Edwards, Alexis C.;Hottenga, Jouke J.;Grotzinger, Andrew D.;Gustavson, Daniel E.;Jennings, Mariela, V;Anokhin, Andrey;Dick, Danielle M.;Edenberg, Howard J.;Kramer, John R.;Lai, Dongbing;Meyers, Jacquelyn L.;Pandey, Ashwini K.;Harden, Kathryn Paige;Nivard, Michel G.;de Geus, Eco J. C.;Boomsma, Dorret, I;Agrawal, Arpana;Davis, Lea K.;Clarke, Toni-Kim;Palmer, Abraham A.;Sanchez-Roige, Sandra
酒精使用障碍识别测试（AUDIT）的全基因组关联研究（GWAS），酒精使用障碍（AUD）的十项筛选，阐明了酒精消费和滥用的新位点。然而，这些研究也表明，GWAS可能受到许多偏见的影响（例如，测量误差，选择偏差），这可能导致酒精参与和AUD之间不一致的遗传相关性，以及酒精参与和精神疾病/医学状况之间矛盾的负遗传相关性。为了探索遗传相关性中这些意想不到的差异，我们进行了AUDIT项目的第一个项目级别和最大GWAS（N= 160，824），并应用多变量框架来减轻先前的偏倚。我们确定了审计项目之间的相似性（和不相似性）的新模式，并在遗传水平上发现了相关的双因素结构的证据（消费和问题，rg= 0.80）。此外，通过对每个AUDIT项目应用计算机衍生的权重，我们构建了一个酒精消费的综合指标，该指标与酒精依赖（rg= 0.67）和其他几种精神疾病密切相关，与健康和积极的社会经济结果不再呈正相关。最后，通过在三个独立的队列中进行多基因分析，这些队列在确定和患病率方面存在差异，我们确定了饮酒，酒精滥用和人类健康之间的新遗传关联。我们的工作进一步强调了AUDIT对AUD的临床和遗传研究的价值，以及使用多变量方法研究与AUD更密切相关的遗传关联的重要性。
Genome-wide association studies (GWASs) of the Alcohol Use Disorders Identification Test (AUDIT), a ten-item screener for alcohol use disorders (AUD), have elucidated novel loci for alcohol consumption and misuse. However, these studies also revealed that GWASs can be influenced by numerous biases (e.g., measurement error, selection bias), which may have led to inconsistent genetic correlations between alcohol involvement and AUD, as well as paradoxically negative genetic correlations between alcohol involvement and psychiatric disorders/medical conditions. To explore these unexpected differences in genetic correlations, we conducted the first item-level and largest GWAS of AUDIT items (N=160,824), and applied a multivariate framework to mitigate previous biases. We identified novel patterns of similarity (and dissimilarity) among the AUDIT items, and found evidence of a correlated two-factor structure at the genetic level (Consumption and Problems, rg=.80). Moreover, by applying empirically-derived weights to each of the AUDIT items, we constructed an aggregate measure of alcohol consumption that is strongly associated with alcohol dependence (rg=.67) and several other psychiatric disorders, and no longer positively associated with health and positive socioeconomic outcomes. Lastly, by conducting polygenic analyses in three independent cohorts that differed in their ascertainment and prevalence of AUD, we identified novel genetic associations between alcohol consumption, alcohol misuse, and human health. Our work further emphasizes the value of AUDIT for both clinical and genetic studies of AUD, and the importance of using multivariate methods to study genetic associations that are more closely related to AUD.
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影响因子：
11
作者：
Davies G;Marioni RE;Liewald DC;Hill WD;Hagenaars SP;Harris SE;Ritchie SJ;Luciano M;Fawns-Ritchie C;Lyall D;Cullen B;Cox SR;Hayward C;Porteous DJ;Evans J;McIntosh AM;Gallacher J;Craddock N;Pell JP;Smith DJ;Gale CR;Deary IJ
通讯作者：
Deary IJ
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：
5
作者：
Fry A;Littlejohns TJ;Sudlow C;Doherty N;Adamska L;Sprosen T;Collins R;Allen NE
通讯作者：
Allen NE
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：
9.2
作者：
Chang CC;Chow CC;Tellier LC;Vattikuti S;Purcell SM;Lee JJ
通讯作者：
Lee JJ