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评估美国 HIV 感染者中已知遗传变异与物质使用之间的关联。

Assessing the associations between known genetic variants and substance use in people with HIV in the United States.

机构信息

Department of Epidemiology, University of Washington, Seattle, WA, United States of America.

Department of Medicine, University of Washington, Seattle, WA, United States of America.

出版信息

PLoS One. 2023 Oct 5;18(10):e0292068. doi: 10.1371/journal.pone.0292068. eCollection 2023.

Abstract

BACKGROUND

The prevalence of substance use in people with HIV (PWH) in the United States is higher than in the general population and is an important driver of HIV-related outcomes. We sought to assess if previously identified genetic associations that contribute to substance use are also observed in a population of PWH.

METHODS

We performed genome-wide association studies (GWAS) of alcohol, smoking, and cannabis use phenotypes in a multi-ancestry population of 7,542 PWH from the Center for AIDS Research Network of Integrated Clinical Systems (CNICS). We conducted multi-ancestry GWAS for individuals of African (n = 3,748), Admixed American (n = 1,334), and European (n = 2,460) ancestry. Phenotype data were self-reported and collected using patient reported outcomes (PROs) and three questions from AUDIT-C, an alcohol screening tool. We analyzed nine phenotypes: 1) frequency of alcohol consumption, 2) typical number of drinks on a day when drinking alcohol, 3) frequency of five or more alcoholic drinks in a 30-day period, 4) smoking initiation, 5) smoking cessation, 6) cigarettes per day, 7) cannabis use initiation, 8) cannabis use cessation, 9) frequency of cannabis use during the previous 30 days. For each phenotype we considered a) variants previously identified as associated with a substance use trait and b) novel associations.

RESULTS

We observed evidence for effects of previously reported single nucleotide polymorphisms (SNPs) related to alcohol (rs1229984, p = 0.001), tobacco (rs11783093, p = 2.22E-4), and cannabis use (rs2875907, p = 0.005). We also report two novel loci (19p13.2, p = 1.3E-8; and 20p11.21, p = 2.1E-8) associated with cannabis use cessation.

CONCLUSIONS

Our analyses contribute to understanding the genetic bases of substance use in a population with relatively higher rates of use compared to the general population.

摘要

背景

美国艾滋病毒感染者(PWH)的物质使用流行率高于一般人群,是与艾滋病毒相关结果的重要驱动因素。我们试图评估以前确定的与物质使用有关的遗传关联是否也存在于 PWH 人群中。

方法

我们对来自艾滋病研究中心综合临床系统网络(CNICS)的 7542 名多血统 PWH 进行了酒精、吸烟和大麻使用表型的全基因组关联研究(GWAS)。我们对非洲血统个体(n = 3748)、混合血统美国人(n = 1334)和欧洲血统个体(n = 2460)进行了多血统 GWAS。表型数据是通过患者报告的结果(PROs)和 AUDIT-C 中的三个问题(一种酒精筛查工具)进行自我报告收集的。我们分析了九个表型:1)饮酒频率,2)饮酒日典型饮酒量,3)30 天内五次或更多含酒精饮料的频率,4)吸烟开始,5)戒烟,6)每天吸烟量,7)大麻使用开始,8)大麻使用停止,9)过去 30 天内大麻使用频率。对于每种表型,我们考虑了 a)先前确定与物质使用特征相关的变异,以及 b)新的关联。

结果

我们观察到先前报道的与酒精(rs1229984,p = 0.001)、烟草(rs11783093,p = 2.22E-4)和大麻使用(rs2875907,p = 0.005)相关的单核苷酸多态性(SNP)相关效应的证据。我们还报告了两个新的基因座(19p13.2,p = 1.3E-8;20p11.21,p = 2.1E-8)与大麻使用停止相关。

结论

我们的分析有助于了解与一般人群相比使用频率相对较高的人群中物质使用的遗传基础。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/245d/10553320/64005e36d872/pone.0292068.g001.jpg

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