Alcohol and nicotine polygenic scores are associated with the development of alcohol and nicotine use problems from adolescence to young adulthood.
Alcohol and nicotine polygenic scores are associated with the development of alcohol and nicotine use problems from adolescence to young adulthood.
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DOI：
10.1111/add.15697
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发表时间：
2022-04
期刊：
影响因子：
--
通讯作者：
Hicks BM
中科院分区：
文献类型：
--
作者：
Deak JD;Clark DA;Liu M;Schaefer JD;Jang SK;Durbin CE;Iacono WG;McGue M;Vrieze S;Hicks BM
酒精和尼古丁使用的分子遗传学研究已经确定了许多全基因组关联研究（GWAS）位点。我们测量了饮酒和吸烟多基因评分（PGS）与从儿童晚期到成年早期酒精和尼古丁使用结果的轨迹之间的关联，物质特异性与更广泛责任的PGS效应，以及PGS表现是否因消费与有问题的物质使用而变化。我们将具有结构化残差的潜在增长曲线模型与14至34岁的酒精和尼古丁使用和问题的测量分数相拟合。然后，我们估计了截距（初始状态）和斜率（变化率）参数与每周饮酒量（DPW），问题酒精使用（PAU），每天吸烟量（CPD）和经常吸烟者（SMK）之间的关联，控制性别和遗传主成分。所有数据均在美国进行分析。使用迄今为止最大的酒精和尼古丁摄入量和问题使用GWAS的结果，计算明尼苏达州双胞胎家庭研究（n = 3225）参与者的PGS。每个PGS都与其各自物质的使用轨迹相关[即DPW（β平均值= 0.08; β范围= 0.02-0.12）和PAU（酒精的β平均值= 0.12; β范围= −0.02 - 0.31）;尼古丁的CPD（β平均值= 0.08; β范围= 0.04-0.14）和SMK（β平均值= 0.18; β范围= 0.05-0.36）]。PAU和SMK PGS还显示出跨物质关联（即PAU用于尼古丁特异性拦截，SMK用于酒精拦截和斜率）。所有确定的SMK PGS效应仍然是尼古丁和酒精轨迹的显著预测因子（β平均值= 0.15; β范围= 0.02-0.33），即使在调整所有其他PGS的相应效应后。物质使用相关的多基因评分（PGSs）随着时间的推移，其与物质使用和问题的关联的强度和一般性与特异性不同。经常吸烟的PGS似乎是物质使用轨迹的一个强有力的预测因子，并且似乎可以测量物质使用的尼古丁特异性和非特异性遗传责任，以及一般潜在的外部化问题。
Molecular genetic studies of alcohol and nicotine use have identified many genome-wide association study (GWAS) loci. We measured associations between drinking and smoking polygenic scores (PGS) and trajectories of alcohol and nicotine use outcomes from late childhood to early adulthood, substance-specific versus broader-liability PGS effects, and if PGS performance varied for consumption versus problematic substance use. We fitted latent growth curve models with structured residuals to scores on measures of alcohol and nicotine use and problems from ages 14 to 34 years. We then estimated associations between the intercept (initial status) and slope (rate of change) parameters and PGSs for drinks per week (DPW), problematic alcohol use (PAU), cigarettes per day (CPD) and ever being a regular smoker (SMK), controlling for sex and genetic principal components. All data were analyzed in the United States. PGSs were calculated for participants of the Minnesota Twin Family Study (n = 3225) using results from the largest GWAS of alcohol and nicotine consumption and problematic use to date. Each PGS was associated with trajectories of use for their respective substances [i.e. DPW (βmean = 0.08; βrange = 0.02–0.12) and PAU (βmean = 0.12; βrange = −0.02 to 0.31) for alcohol; CPD (βmean = 0.08; βrange = 0.04–0.14) and SMK (βmean = 0.18; βrange = 0.05–0.36) for nicotine]. The PAU and SMK PGSs also exhibited cross-substance associations (i.e. PAU for nicotine-specific intercepts and SMK for alcohol intercepts and slope). All identified SMK PGS effects remained as significant predictors of nicotine and alcohol trajectories (βmean = 0.15; βrange = 0.02–0.33), even after adjusting for the respective effects of all other PGSs. Substance use-related polygenic scores (PGSs) vary in the strength and generality versus specificity of their associations with substance use and problems over time. The regular smoking PGS appears to be a robust predictor of substance use trajectories and seems to measure both nicotine-specific and non-specific genetic liability for substance use, and potentially externalizing problems in general.
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影响因子：
30.8
作者：
Das, Sayantan;Forer, Lukas;Schoenherr, Sebastian;Sidore, Carlo;Locke, Adam E.;Kwong, Alan;Vrieze, Scott I.;Chew, Emily Y.;Levy, Shawn;McGue, Matt;Schlessinger, David;Stambolian, Dwight;Loh, Po-Ru;Iacono, William G.;Swaroop, Anand;Scott, Laura J.;Cucca, Francesco;Kronenberg, Florian;Boehnke, Michael;Abecasis, Goncalo R.;Fuchsberger, Christian
通讯作者：
Fuchsberger, Christian
DOI：
10.1056/nejmoa1605086
发表时间：
2016-12-15
期刊：
The New England journal of medicine
影响因子：
--
作者：
Khera AV;Emdin CA;Drake I;Natarajan P;Bick AG;Cook NR;Chasman DI;Baber U;Mehran R;Rader DJ;Fuster V;Boerwinkle E;Melander O;Orho-Melander M;Ridker PM;Kathiresan S
通讯作者：
Kathiresan S
影响因子：
9.2
作者：
Chang CC;Chow CC;Tellier LC;Vattikuti S;Purcell SM;Lee JJ
通讯作者：
Lee JJ
影响因子：
16.6
作者：
Kranzler, Henry R.;Zhou, Hang;Gelernter, Joel
通讯作者：
Gelernter, Joel
明尼苏达双胞胎家庭研究的富集研究：增加了外部化精神病理风险高风险的双胞胎家族的产量。
DOI：
10.1375/twin.12.5.489
发表时间：
2009-10
期刊：
Twin research and human genetics : the official journal of the International Society for Twin Studies
影响因子：
--
作者：
Keyes MA;Malone SM;Elkins IJ;Legrand LN;McGue M;Iacono WG
通讯作者：
Iacono WG