Department of Psychiatry, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.
Department of Psychiatry, Washington University School of Medicine, Saint Louis, Missouri, USA.
Addict Biol. 2021 Jan;26(1):e12880. doi: 10.1111/adb.12880. Epub 2020 Feb 16.
Eating disorders and substance use disorders frequently co-occur. Twin studies reveal shared genetic variance between liabilities to eating disorders and substance use, with the strongest associations between symptoms of bulimia nervosa and problem alcohol use (genetic correlation [r ], twin-based = 0.23-0.53). We estimated the genetic correlation between eating disorder and substance use and disorder phenotypes using data from genome-wide association studies (GWAS). Four eating disorder phenotypes (anorexia nervosa [AN], AN with binge eating, AN without binge eating, and a bulimia nervosa factor score), and eight substance-use-related phenotypes (drinks per week, alcohol use disorder [AUD], smoking initiation, current smoking, cigarettes per day, nicotine dependence, cannabis initiation, and cannabis use disorder) from eight studies were included. Significant genetic correlations were adjusted for variants associated with major depressive disorder and schizophrenia. Total study sample sizes per phenotype ranged from ~2400 to ~537 000 individuals. We used linkage disequilibrium score regression to calculate single nucleotide polymorphism-based genetic correlations between eating disorder- and substance-use-related phenotypes. Significant positive genetic associations emerged between AUD and AN (r = 0.18; false discovery rate q = 0.0006), cannabis initiation and AN (r = 0.23; q < 0.0001), and cannabis initiation and AN with binge eating (r = 0.27; q = 0.0016). Conversely, significant negative genetic correlations were observed between three nondiagnostic smoking phenotypes (smoking initiation, current smoking, and cigarettes per day) and AN without binge eating (r = -0.19 to -0.23; qs < 0.04). The genetic correlation between AUD and AN was no longer significant after co-varying for major depressive disorder loci. The patterns of association between eating disorder- and substance-use-related phenotypes highlights the potentially complex and substance-specific relationships among these behaviors.
饮食障碍和物质使用障碍经常同时发生。双胞胎研究揭示了饮食障碍和物质使用倾向之间的共同遗传差异，其中神经性贪食症和酒精使用问题之间的关联最强（遗传相关系数[r]，基于双胞胎=0.23-0.53）。我们使用全基因组关联研究（GWAS）的数据，估计了饮食障碍和物质使用障碍及表型之间的遗传相关性。纳入了四种饮食障碍表型（神经性厌食症[AN]、伴有暴食的 AN、不伴有暴食的 AN 和神经性贪食症因子评分）和八种与物质使用相关的表型（每周饮酒量、酒精使用障碍[AUD]、吸烟起始、当前吸烟、每天吸烟量、尼古丁依赖、大麻起始和大麻使用障碍），来自八项研究。对每种表型的调整后显著遗传相关性与与重度抑郁症和精神分裂症相关的变体有关。每种表型的总研究样本量从2400 到537000 人不等。我们使用连锁不平衡评分回归来计算饮食障碍和物质使用相关表型之间基于单核苷酸多态性的遗传相关性。在 AUD 和 AN（r=0.18；假发现率 q=0.0006）、大麻起始和 AN（r=0.23；q<0.0001）以及大麻起始和伴有暴食的 AN（r=0.27；q=0.0016）之间出现了显著的正遗传关联。相反，在共变异重度抑郁症位点后，在三个非诊断性吸烟表型（吸烟起始、当前吸烟和每天吸烟量）和不伴有暴食的 AN（r=-0.19 到-0.23；qs<0.04）之间观察到显著的负遗传相关性。AUD 和 AN 之间的遗传相关性在共变重度抑郁症位点后不再显著。饮食障碍和物质使用相关表型之间的关联模式突出了这些行为之间潜在的复杂和物质特异性关系。
