Journal
CEREBRAL CORTEX
Volume 32, Issue 4, Pages 796-807Publisher
OXFORD UNIV PRESS INC
DOI: 10.1093/cercor/bhab243
Keywords
alcohol use; cannabis use; genetics; neuroimaging; smoking behavior
Categories
Funding
- Australian National Health & Medical Research Council through an NHMRC-ARC Dementia Research Development Fellowship [GNT1002821]
- Australian Research Council through an NHMRC-ARC Dementia Research Development Fellowship [GNT1002821]
- National Institutes of Health [U01DA041048, U01DA050989, U01DA051016, U01DA041022, U01DA051018, U01DA051037, U01DA050987, U01DA041174, U01DA041106, U01DA041117, U01DA041028, U01DA041134]
- The National Institutes of Health [U01 DA050988, U01DA051039, U01DA041156, U01DA041025, U01DA041120, U01DA051038, U01DA041148, U01DA041093, U01DA041089, U24DA041123, U24DA041147]
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The study uncovered a shared genetic etiology between cortical brain morphology and substance use behaviors, suggesting that genetic variants associated with substance use may be causally related to brain structure differences. This may help to better understand the association between brain structure and substance use.
Genome-wide association studies (GWAS) have identified genetic variants associated with brain morphology and substance use behaviors (SUB). However, the genetic overlap between brain structure and SUB has not been well characterized. We leveraged GWAS summary data of 71 brain imaging measures and alcohol, tobacco, and cannabis use to investigate their genetic overlap using linkage disequilibrium score regression. We used genomic structural equation modeling to model a common SUB genetic factor and investigated its genetic overlap with brain structure. Furthermore, we estimated SUB polygenic risk scores (PRS) and examined whether they predicted brain imaging traits using the Adolescent Behavior and Cognitive Development (ABCD) study. We identified 8 significant negative genetic correlations, including between (1) alcoholic drinks per week and average cortical thickness, and (2) intracranial volume with age of smoking initiation. We observed 5 positive genetic correlations, including those between (1) insula surface area and lifetime cannabis use, and (2) the common SUB genetic factor and pericalcarine surface area. SUB PRS were associated with brain structure variation in ABCD. Our findings highlight a shared genetic etiology between cortical brain morphology and SUB and suggest that genetic variants associated with SUB may be causally related to brain structure differences.
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