The effects of alcohol use severity and polygenic risk on gray matter volumes in young adults
IntroductionGenetic factors contribute to alcohol misuse. Chronic alcohol consumption is associated with decreases in gray matter volumes (GMVs) of the brain. However, it remains unclear whether or how genetic risks may alter GMVs independent of the effects of alcohol exposure. MethodsHere, we emplo...
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Frontiers Media S.A.
2025-05-01
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| author | Yu Chen Huey-Ting Li Xingguang Luo Guangfei Li Guangfei Li Jaime S. Ide Chiang-Shan R. Li Chiang-Shan R. Li Chiang-Shan R. Li Chiang-Shan R. Li |
| author_facet | Yu Chen Huey-Ting Li Xingguang Luo Guangfei Li Guangfei Li Jaime S. Ide Chiang-Shan R. Li Chiang-Shan R. Li Chiang-Shan R. Li Chiang-Shan R. Li |
| author_sort | Yu Chen |
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| description | IntroductionGenetic factors contribute to alcohol misuse. Chronic alcohol consumption is associated with decreases in gray matter volumes (GMVs) of the brain. However, it remains unclear whether or how genetic risks may alter GMVs independent of the effects of alcohol exposure. MethodsHere, we employed the Human Connectome Project data of neurotypical adults (n = 995; ages 22-35; 534 women) and, with voxel-based morphometry analysis, computed the GMVs of 166 regions in the automated anatomical atlas 3. Alcohol use behaviors were assessed with the Semi-Structured Assessment for the Genetics of Alcoholism. Alcohol use severity was quantified by the first principal component (PC1) identified of principal component analysis of 15 drinking measures. Polygenic risk scores (PRS) for alcohol dependence were computed for all subjects using the Psychiatric Genomics Consortium study of alcohol dependence as the base sample. With age, sex, race, and total intracranial volume as covariates, we evaluated the relationships of regional GMVs with PC1 and PRS together in a linear regression. ResultsPC1 was negatively correlated with GMVs of right insula and Heschl’s gyrus, and PRS was positively correlated with GMVs of left posterior orbitofrontal cortex, bilateral intralaminar nuclei of the thalamus and lingual gyri. DiscussionThese findings suggest distinct volumetric neural markers of drinking severity and genetic risks of alcohol misuse. Notably, in contrast to volumetric reduction, the genetic risks of dependent drinking may involve larger regional volumes in the reward, emotion, and saliency circuits. |
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| language | English |
| publishDate | 2025-05-01 |
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| series | Frontiers in Psychiatry |
| spelling | doaj-art-c5acfb3ffec441d5bc3510e99bf149b42025-08-20T02:57:29ZengFrontiers Media S.A.Frontiers in Psychiatry1664-06402025-05-011610.3389/fpsyt.2025.15600531560053The effects of alcohol use severity and polygenic risk on gray matter volumes in young adultsYu Chen0Huey-Ting Li1Xingguang Luo2Guangfei Li3Guangfei Li4Jaime S. Ide5Chiang-Shan R. Li6Chiang-Shan R. Li7Chiang-Shan R. Li8Chiang-Shan R. Li9Department of Psychiatry, Yale University School of Medicine, New Haven, CT, United StatesYale College, New Haven, CT, United StatesDepartment of Psychiatry, Yale University School of Medicine, New Haven, CT, United StatesDepartment of Biomedical Engineering, College of Chemistry and Life Science, Beijing University of Technology, Beijing, ChinaBeijing International Science and Technology Cooperation Base for Intelligent Physiological Measurement and Clinical Transformation, Beijing, ChinaDepartment of Psychiatry, Yale University School of Medicine, New Haven, CT, United StatesDepartment of Psychiatry, Yale University School of Medicine, New Haven, CT, United StatesDepartment of Neuroscience, Yale University School of Medicine, New Haven, CT, United StatesInter-Department Neuroscience Program, Yale University, New Haven, CT, United StatesWu Tsai Institute, Yale University, New Haven, CT, United StatesIntroductionGenetic factors contribute to alcohol misuse. Chronic alcohol consumption is associated with decreases in gray matter volumes (GMVs) of the brain. However, it remains unclear whether or how genetic risks may alter GMVs independent of the effects of alcohol exposure. MethodsHere, we employed the Human Connectome Project data of neurotypical adults (n = 995; ages 22-35; 534 women) and, with voxel-based morphometry analysis, computed the GMVs of 166 regions in the automated anatomical atlas 3. Alcohol use behaviors were assessed with the Semi-Structured Assessment for the Genetics of Alcoholism. Alcohol use severity was quantified by the first principal component (PC1) identified of principal component analysis of 15 drinking measures. Polygenic risk scores (PRS) for alcohol dependence were computed for all subjects using the Psychiatric Genomics Consortium study of alcohol dependence as the base sample. With age, sex, race, and total intracranial volume as covariates, we evaluated the relationships of regional GMVs with PC1 and PRS together in a linear regression. ResultsPC1 was negatively correlated with GMVs of right insula and Heschl’s gyrus, and PRS was positively correlated with GMVs of left posterior orbitofrontal cortex, bilateral intralaminar nuclei of the thalamus and lingual gyri. DiscussionThese findings suggest distinct volumetric neural markers of drinking severity and genetic risks of alcohol misuse. Notably, in contrast to volumetric reduction, the genetic risks of dependent drinking may involve larger regional volumes in the reward, emotion, and saliency circuits.https://www.frontiersin.org/articles/10.3389/fpsyt.2025.1560053/fullHCPalcohol dependencepolygenic risk scoreVBMthalamus |
| spellingShingle | Yu Chen Huey-Ting Li Xingguang Luo Guangfei Li Guangfei Li Jaime S. Ide Chiang-Shan R. Li Chiang-Shan R. Li Chiang-Shan R. Li Chiang-Shan R. Li The effects of alcohol use severity and polygenic risk on gray matter volumes in young adults Frontiers in Psychiatry HCP alcohol dependence polygenic risk score VBM thalamus |
| title | The effects of alcohol use severity and polygenic risk on gray matter volumes in young adults |
| title_full | The effects of alcohol use severity and polygenic risk on gray matter volumes in young adults |
| title_fullStr | The effects of alcohol use severity and polygenic risk on gray matter volumes in young adults |
| title_full_unstemmed | The effects of alcohol use severity and polygenic risk on gray matter volumes in young adults |
| title_short | The effects of alcohol use severity and polygenic risk on gray matter volumes in young adults |
| title_sort | effects of alcohol use severity and polygenic risk on gray matter volumes in young adults |
| topic | HCP alcohol dependence polygenic risk score VBM thalamus |
| url | https://www.frontiersin.org/articles/10.3389/fpsyt.2025.1560053/full |
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