Behavioural Science Institute, Radboud University, Nijmegen, The Netherlands.
Department of Psychiatry, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands.
Am J Med Genet B Neuropsychiatr Genet. 2021 Oct;186(7):423-429. doi: 10.1002/ajmg.b.32822. Epub 2020 Sep 10.
People with attention-deficit/hyperactivity disorder (ADHD) or other psychiatric disorders show high rates of nicotine dependence (ND). This comorbidity might be (partly) explained by shared genetic factors. Genetic correlations between ND and ADHD (or other psychiatric disorders) have not yet been estimated. A significant genetic correlation might indicate genetic overlap, but could also reflect a causal relationship. In the present study we investigated the genetic correlation (with LD score regression analyses) between ND and ADHD, as well as between ND and other major psychiatric conditions (major depressive disorder, schizophrenia, anxiety, bipolar disorder, autism spectrum, anorexia nervosa, and antisocial behavior) based on the summary statistics of large Genome Wide Association studies. We explored the causal nature of the relationship between ND and ADHD using two-sample Mendelian randomization. We found a high genetic correlation between ND and ADHD (r = .53, p = 1.85 × 10 ), and to a lesser extent also between ND-major depressive disorder (r = .42, p = 3.6 × 10 ) and ND-schizophrenia (r = .18, p = 1.1 × 10 ). We did not find evidence for a causal relationship from liability for ADHD to ND (which could be due to a lack of power). The strong genetic correlations might reflect different phenotypic manifestations of (partly) shared underlying genetic vulnerabilities. Combined with the lack of evidence for a causal relationship from liability for ADHD to ND, these findings stress the importance to further investigate the underlying genetic vulnerability explaining co-morbidity in psychiatric disorders.
患有注意力缺陷多动障碍（ADHD）或其他精神疾病的人表现出较高的尼古丁依赖（ND）率。这种共病可能部分归因于共同的遗传因素。ND 和 ADHD（或其他精神疾病）之间的遗传相关性尚未得到估计。显著的遗传相关性可能表明存在遗传重叠，但也可能反映出因果关系。在本研究中，我们基于大型全基因组关联研究的汇总统计数据，使用 LD 得分回归分析，调查了 ND 和 ADHD 之间以及 ND 和其他主要精神疾病（重度抑郁症、精神分裂症、焦虑症、双相情感障碍、自闭症谱系障碍、神经性厌食症和反社会行为）之间的遗传相关性。我们使用两样本孟德尔随机化来探索 ND 和 ADHD 之间关系的因果性质。我们发现 ND 和 ADHD 之间存在高度的遗传相关性（r =.53，p = 1.85×10 ），并且在 ND-重度抑郁症（r =.42，p = 3.6×10 ）和 ND-精神分裂症（r =.18，p = 1.1×10 ）之间也存在较小程度的遗传相关性。我们没有发现从 ADHD 的易感性到 ND 的因果关系的证据（这可能是由于缺乏效力）。强烈的遗传相关性可能反映了（部分）共同潜在遗传脆弱性的不同表型表现。结合 ADHD 的易感性到 ND 缺乏因果关系的证据，这些发现强调了进一步研究解释精神障碍共病的潜在遗传脆弱性的重要性。
