Virginia Institute for Psychiatric and Behavioral Genetics, Virginia Commonwealth University, Richmond, Virginia.
Department of Psychiatry, Virginia Commonwealth University, Richmond, Virginia.
J Stud Alcohol Drugs. 2023 May;84(3):361-367. doi: 10.15288/jsad.22-00359. Epub 2023 Jan 16.
The purpose of this study was to determine, using a top-down genetic analysis, the degree of specificity of the genetic risk factors for individual forms of substance use disorders (SUD).
We examined and followed to December 31, 2018, all individuals born in Sweden between 1960 and 1990 ( = 2,772,752) diagnosed with any of the following six SUDs: alcohol use disorder (AUD), drug use disorder (DUD), or one of four specific forms of DUD involving cannabis (CUD), cocaine and other stimulants (CSUD), opioids (OUD), or sedatives (SeUD). We examined population subsamples at high versus median genetic liability to each of these SUDs. In those samples, we then examined the prevalence of our SUDs in the high versus median liability groups, expressed as a tetrachoric correlation. Genetic liability was assessed by a family genetic risk score.
All SUDs were concentrated in those at high versus median risk for all six groups. DUD, CUD, and CSUD showed modest genetic specificity in that they were more concentrated in samples with high genetic liability to each of them than were other SUDs. The differences, however, were modest. No evidence for genetic specificity was seen for AUD, OUD, and SeUD, as other disorders were equally or more concentrated in those at high versus median genetic risk for that form of SUD.
Individuals at high genetic risk for particular forms of SUD typically had elevated rates for all forms of SUDs, consistent with the nonspecificity of much of SUD genetic liability. Evidence of specificity of genetic risk for particular forms of SUD was noted but was quantitatively modest.
本研究旨在通过自上而下的遗传分析，确定个体物质使用障碍（SUD）各亚型的遗传风险因素的特异性程度。
我们对 1960 年至 1990 年期间在瑞典出生的所有个体进行了检查和随访，直到 2018 年 12 月 31 日，这些个体被诊断为以下六种 SUD 中的任何一种：酒精使用障碍（AUD）、药物使用障碍（DUD）或涉及大麻（CUD）、可卡因和其他兴奋剂（CSUD）、阿片类药物（OUD）或镇静剂（SeUD）的四种特定形式的 DUD。我们在高遗传易感性和中等遗传易感性的人群亚组中检查了这些 SUD。在这些样本中，我们然后检查了高易感性和中等易感性组中每种 SUD 的患病率，用四因素相关表示。遗传易感性通过家族遗传风险评分来评估。
所有 SUD 都集中在对所有六组高遗传易感性和中等遗传易感性的人群中。DUD、CUD 和 CSUD 表现出一定程度的遗传特异性，因为与其他 SUD 相比，它们在对每种 SUD 高遗传易感性的样本中更为集中。然而，这些差异很小。对于 AUD、OUD 和 SeUD，没有遗传特异性的证据，因为其他障碍在对该形式 SUD 高遗传风险的人群中同样或更集中。
特定形式 SUD 的高遗传风险个体通常具有所有形式 SUD 的较高发病率，这与 SUD 遗传易感性的非特异性一致。注意到特定形式 SUD 的遗传风险特异性的证据，但数量上较小。
