Gurriarán Xaquín, Rodríguez-López Julio, Flórez Gerardo, Pereiro César, Fernández José M, Fariñas Emilio, Estévez Valentín, Arrojo Manuel, Costas Javier
Instituto de Investigación Sanitaria (IDIS) de Santiago de Compostela, Complexo Hospitalario Universitario de Santiago de Compostela (CHUS), Servizo Galego de Saúde (SERGAS), Santiago de Compostela, Galicia, Spain.
Unidade de Conductas Adictivas, Servizo de Psiquiatría, Complexo Hospitalario Universitario de Ourense (CHUO), Servizo Galego de Saúde (SERGAS), Ourense, Galicia, Spain.
Genes Brain Behav. 2019 Mar;18(3):e12504. doi: 10.1111/gbb.12504. Epub 2018 Jul 19.
Genetic susceptibility to substance use disorders (SUDs) is partially shared between substances. Heritability of any substance dependence, estimated as 54%, is partly explained by additive effects of common variants. Comorbidity between SUDs and other psychiatric disorders is frequent. The present study aims to analyze the additive role of common variants in this comorbidity using polygenic scores (PGSs) based on genome-wide association study discovery samples of schizophrenia (SCZ), bipolar disorder, attention-deficit/hyperactivity disorder, autism spectrum disorder, major depressive disorder and anxiety disorders, available from large consortia. PGSs were calculated for 534 patients meeting DSM-IV criteria for dependence of a substance and abuse/dependence of another substance between alcohol, tobacco, cannabis, cocaine, opiates, hypnotics, stimulants, hallucinogens and solvents; and 587 blood donors from the same population, Iberians from Galicia, as controls. Significance of the PGS and percentage of variance explained were calculated by logistic regression. Using discovery samples of similar size, significant associations with SUDs were detected for SCZ PGS. SCZ PGS explained more variance in SUDs than in most psychiatric disorders. Cross-disorder PGS based on five psychiatric disorders was significant after adjustment for the effect of SCZ PGS. SCZ PGS was significantly higher in women than in men abusing alcohol. Our findings indicate that SUDs share genetic susceptibility with SCZ to a greater extent than with other psychiatric disorders, including externalizing disorders such as attention-deficit/hyperactivity disorder. Women have lower probability to develop substance abuse/dependence than men at similar PGS probably because of a higher social pressure against excessive drug use in women.
物质使用障碍（SUDs）的遗传易感性在不同物质之间存在部分共享。任何物质依赖的遗传度估计为54%，部分可由常见变异的加性效应来解释。SUDs与其他精神障碍之间的共病情况很常见。本研究旨在利用基于精神分裂症（SCZ）、双相情感障碍、注意力缺陷多动障碍、自闭症谱系障碍、重度抑郁症和焦虑症的全基因组关联研究发现样本的多基因评分（PGSs），分析常见变异在这种共病中的加性作用，这些样本可从大型研究联盟获得。对534名符合《精神疾病诊断与统计手册第四版》（DSM-IV）标准的患者计算PGSs，这些患者存在一种物质依赖以及酒精、烟草、大麻、可卡因、阿片类药物、催眠药、兴奋剂、致幻剂和溶剂中另一种物质的滥用/依赖情况；并以587名来自同一人群（加利西亚的伊比利亚人）的献血者作为对照。通过逻辑回归计算PGS的显著性以及解释的方差百分比。使用相似规模的发现样本，检测到SCZ PGS与SUDs存在显著关联。SCZ PGS在SUDs中解释的方差比在大多数精神障碍中更多。在调整SCZ PGS的影响后，基于五种精神障碍的跨疾病PGS具有显著性。在滥用酒精的女性中，SCZ PGS显著高于男性。我们的研究结果表明，SUDs与SCZ共享的遗传易感性程度高于与其他精神障碍，包括注意力缺陷多动障碍等外化性障碍。在相似的PGS水平下，女性发生物质滥用/依赖的概率低于男性，这可能是因为社会对女性过度使用药物的压力更大。
