TY - JOUR
T1 - Polygenic risk scores for alcohol involvement relate to brain structure in substance-naïve children
T2 - Results from the ABCD study
AU - Hatoum, Alexander S.
AU - Johnson, Emma C.
AU - Baranger, David A.A.
AU - Paul, Sarah E.
AU - Agrawal, Arpana
AU - Bogdan, Ryan
N1 - Funding Information:
Summary statistics and data are publicly available through various sources. The Million Veterans Project summary statistics were accessed via dbGaP (phs001672.v1.p1) as part of #24806: Neurobiological bases of psychiatric traits. The authors thank Million Veteran Program (MVP) staff, researchers, and volunteers, who have contributed to MVP, and especially participants who previously served their country in the military and now generously agreed to enroll in the study. (See https://www.research.va.gov/mvp/ for more details). The citation for MVP is Gaziano, J.M. et al. Million Veteran Program: A mega‐biobank to study genetic influences on health and disease. J Clin Epidemiol 70, 214‐23 (2016). This research is based on data from the Million Veteran Program, Office of Research and Development, Veterans Health Administration, and was supported by the Veterans Administration (VA) Cooperative Studies Program (CSP) award #G002. Data for this study were provided by the Adolescent Brain Cognitive Development (ABCD) study, which was funded by awards U01DA041022, U01DA041025, U01DA041028, U01DA041048, U01DA041089, U01DA041093, U01DA041106, U01DA041117, U01DA041120, U01DA041134, U01DA041148, U01DA041156, U01DA041174, U24DA041123, and U24DA041147 from the NIH and additional federal partners ( https://abcdstudy.org/federal-partners.html ). All data used here in are publicly available through the GSCAN consortium, dbGAP, and the ABCD consortium.
Publisher Copyright:
© 2021 International Behavioural and Neural Genetics Society and John Wiley & Sons Ltd.
PY - 2021
Y1 - 2021
N2 - Brain imaging-derived structural correlates of alcohol involvement have largely been speculated to arise as a consequence of alcohol exposure. However, they may also reflect predispositional risk. In substance naïve children of European ancestry who completed the baseline session of the Adolescent Brain Cognitive Development (ABCD) Study (n = 3013), mixed-effects models estimated whether polygenic risk scores (PRS) for problematic alcohol use (PAU-PRS) and drinks per week (DPW-PRS) are associated with magnetic resonance imaging-derived brain structure phenotypes (i.e., total and regional: cortical thickness, surface area and volume; subcortical volume; white matter volume, fractional anisotropy, mean diffusivity). Follow-up analyses evaluated whether any identified regions were also associated with polygenic risk among substance naïve children of African ancestry (n = 898). After adjustment for multiple testing correction, polygenic risk for PAU was associated with lower volume of the left frontal pole and greater cortical thickness of the right supramarginal gyrus (|βs| > 0.009; ps < 0.001; psfdr < 0.046; r2s < 0.004). PAU PRS and DPW PRS showed nominally significant associations with a host of other regional brain structure phenotypes (e.g., insula surface area and volume). None of these regions showed any, even nominal association among children of African ancestry. Genomic liability to alcohol involvement may manifest as variability in brain structure during middle childhood prior to alcohol use initiation. Broadly, alcohol-related variability in brain morphometry may partially reflect predisposing genomic influence. Larger discovery genome-wide association studies and target samples of diverse ancestries are needed to determine whether observed associations may generalize across ancestral origins.
AB - Brain imaging-derived structural correlates of alcohol involvement have largely been speculated to arise as a consequence of alcohol exposure. However, they may also reflect predispositional risk. In substance naïve children of European ancestry who completed the baseline session of the Adolescent Brain Cognitive Development (ABCD) Study (n = 3013), mixed-effects models estimated whether polygenic risk scores (PRS) for problematic alcohol use (PAU-PRS) and drinks per week (DPW-PRS) are associated with magnetic resonance imaging-derived brain structure phenotypes (i.e., total and regional: cortical thickness, surface area and volume; subcortical volume; white matter volume, fractional anisotropy, mean diffusivity). Follow-up analyses evaluated whether any identified regions were also associated with polygenic risk among substance naïve children of African ancestry (n = 898). After adjustment for multiple testing correction, polygenic risk for PAU was associated with lower volume of the left frontal pole and greater cortical thickness of the right supramarginal gyrus (|βs| > 0.009; ps < 0.001; psfdr < 0.046; r2s < 0.004). PAU PRS and DPW PRS showed nominally significant associations with a host of other regional brain structure phenotypes (e.g., insula surface area and volume). None of these regions showed any, even nominal association among children of African ancestry. Genomic liability to alcohol involvement may manifest as variability in brain structure during middle childhood prior to alcohol use initiation. Broadly, alcohol-related variability in brain morphometry may partially reflect predisposing genomic influence. Larger discovery genome-wide association studies and target samples of diverse ancestries are needed to determine whether observed associations may generalize across ancestral origins.
KW - DTI
KW - adolescence
KW - alcohol use
KW - alcohol use disorder
KW - cortical gray matter
KW - drug naive
KW - imaging genetics
KW - multi-site study
KW - polygenic risk scores
KW - subcortical gray matter
UR - http://www.scopus.com/inward/record.url?scp=85108826307&partnerID=8YFLogxK
U2 - 10.1111/gbb.12756
DO - 10.1111/gbb.12756
M3 - Article
C2 - 34092032
AN - SCOPUS:85108826307
JO - Genes, Brain and Behavior
JF - Genes, Brain and Behavior
SN - 1601-1848
ER -