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_g = .53, p = 1.85 × 10⁻¹³), and to a lesser extent also between ND-major depressive disorder (r_g = .42, p = 3.6 × 10⁻¹¹) and ND-schizophrenia (r_g = .18, p = 1.1 × 10⁻³). 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.

中文翻译：

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在更广泛的精神病学背景下调查尼古丁依赖与 ADHD 之间的遗传相关性和因果关系

患有注意力缺陷/多动障碍 (ADHD) 或其他精神疾病的人表现出很高的尼古丁依赖 (ND) 率。这种合并症可能（部分）由共同的遗传因素解释。尚未估计 ND 和 ADHD（或其他精神疾病）之间的遗传相关性。显着的遗传相关性可能表明遗传重叠，但也可能反映因果关系。在本研究中，我们调查了 ND 与 ADHD 之间以及 ND 与其他主要精神疾病（重度抑郁症、精神分裂症、焦虑症、双相情感障碍、自闭症谱系、神经性厌食症和反社会行为）基于大型全基因组关联研究的汇总统计数据。我们使用两样本孟德尔随机化探索了 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 _g  = .53, p  = 1.85 × 10 ^-13 )，并且在较小程度上也介于 ND-重度抑郁症 ( r _g  = .42, p  = 3.6 × 10 ^-11 ) 和 ND-精神分裂症 ( r _g  = .18，p  = 1.1 × 10 ^-3）。我们没有找到证据表明 ADHD 责任与 ND 之间存在因果关系（这可能是由于缺乏权力）。强烈的遗传相关性可能反映了（部分）共享潜在遗传脆弱性的不同表型表现。再加上缺乏证据表明 ADHD 责任与 ND 之间存在因果关系，这些发现强调了进一步研究解释精神疾病合并症的潜在遗传脆弱性的重要性。