Attention-deficit/hyperactivity disorder and lifetime cannabis use: genetic overlap and causality.
Attention-deficit/hyperactivity disorder and lifetime cannabis use: genetic overlap and causality.
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DOI：
10.1038/s41380-018-0339-3
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发表时间：
2020-10
影响因子：
11
通讯作者：
Ribasés M
中科院分区：
文献类型：
--
作者：
Soler Artigas M;Sánchez-Mora C;Rovira P;Richarte V;Garcia-Martínez I;Pagerols M;Demontis D;Stringer S;ADHD Group of the Psychiatric Genomics Consortium, International Cannabis Consortium;Vink JM;Børglum AD;Neale BM;Franke B;Faraone SV;Casas M;Ramos-Quiroga JA;Ribasés M
注意力缺陷多动障碍（ADHD）是一种严重损害神经发育的疾病，在儿童和青少年中的患病率为5%，在成人中为2.5%。多动症的共病状况在症状进展、疾病进程和结果中发挥着关键作用。ADHD与物质使用、滥用和依赖的风险显著增加有关。ADHD和大麻使用部分由遗传因素决定; ADHD的遗传率估计为70-80%，大麻使用的遗传率估计为40- 48%。在这项研究中，我们使用了ADHD（n=53 293）和大麻终生使用（n=32 330）的全基因组关联研究（GWAS）的最大可用荟萃分析的汇总统计数据，以深入了解这两个特征的遗传重叠和因果关系。我们估计它们的遗传相关系数为r2=0.29（P=1.63×10−5），并在交叉性状分析中确定了四个新的全基因组显著位点：单变量关联分析（rs 145108385，P=3.30×10−8和rs 4259397，P=4.52×10−8）和两个基于基因的关联分析（WDPCP，P=9.67×10−7和ZNF 251，P=1.62×10−6）。使用双样本孟德尔随机化方法，我们发现ADHD是终生使用大麻的因果关系，ADHD患者与无ADHD患者相比使用大麻的优势比为7.9（95% CI（3.72，15.51），P=5.88×10−5）。这些结果证实了ADHD和未来大麻使用之间的时间关系，并加强了在临床干预中考虑ADHD背景下药物滥用的必要性。
Attention-deficit/hyperactivity disorder (ADHD) is a severely impairing neurodevelopmental disorder with a prevalence of 5% in children and adolescents and of 2.5% in adults. Comorbid conditions in ADHD play a key role in symptom progression, disorder course and outcome. ADHD is associated with a significantly increased risk for substance use, abuse and dependence. ADHD and cannabis use are partly determined by genetic factors; the heritability of ADHD is estimated at 70–80% and of cannabis use initiation at 40–48%. In this study, we used summary statistics from the largest available meta-analyses of genome-wide association studies (GWAS) of ADHD (n=53 293) and lifetime cannabis use (n=32 330) to gain insights into the genetic overlap and causal relationship of these two traits. We estimated their genetic correlation to be r2=0.29 (P=1.63×10−5) and identified four new genome-wide significant loci in a cross-trait analysis: two in a single variant association analysis (rs145108385, P=3.30×10−8 and rs4259397, P=4.52×10−8) and two in a gene-based association analysis (WDPCP, P=9.67×10−7 and ZNF251, P=1.62×10−6). Using a two-sample Mendelian randomization approach we found support that ADHD is causal for lifetime cannabis use, with an odds ratio of 7.9 for cannabis use in individuals with ADHD in comparison to individuals without ADHD (95% CI (3.72, 15.51), P=5.88×10−5). These results substantiate the temporal relationship between ADHD and future cannabis use and reinforce the need to consider substance misuse in the context of ADHD in clinical interventions.
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来自1,092个人基因组的遗传变异的综合图。
影响因子：
64.8
作者：
通讯作者：
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注意力缺陷多动障碍的遗传学。
影响因子：
11
作者：
Faraone SV;Larsson H
通讯作者：
Larsson H
影响因子：
2.1
作者：
Bowden J;Davey Smith G;Haycock PC;Burgess S
通讯作者：
Burgess S
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：
11
作者：
Franke, B.;Faraone, S. V.;Asherson, P.;Buitelaar, J.;Bau, C. H. D.;Ramos-Quiroga, J. A.;Mick, E.;Grevet, E. H.;Johansson, S.;Haavik, J.;Lesch, K-P;Cormand, B.;Reif, A.
通讯作者：
Reif, A.