Association of genetic copy number variations at 11 q14.2 with brain regional volume differences in an alcohol use disorder population.
This study investigates the relationship between genetic copy number variations and brain volume differences in an alcohol use disorder (AUD) population. We hypothesized that copy number variations may influence subject's risk for alcohol use disorders through variations in regional gray and white matter brain volumes. Since genetic influences upon behavior are the result of many complicated interactions we focus on differences in brain volume as a putative intermediate phenotype between genetic variation and behavior. Copy number variation, alcohol use assessments and brain structural magnetic resonance images from 283 subjects, 199 male and 84 females who were enrolled in two AUD studies were obtained and analyzed using a combination of the Freesurfer image analysis suite and independent component analysis. Because brain volume varies by age we compared participant's volume variation with that derived from a control cohort of 75 subjects. In addition we also regressed out the possible brain volume changes induced by long term alcohol consumption. Small cerebral cortex, cerebellar and caudate along with large cerebral white matter and 5th ventricle volumes are shown to be significantly associated with increased AUD severity. When these volume variations are compared with control subject volumes; the variations seen in subjects with AUD are markedly different from normal aging effects. CNVs at 11 q14.2 are marginally (p < 0.05 uncorrected) correlated with such brain volume variations and the correlation holds true after controlling for long-term alcohol consumption; deletion carriers have smaller cerebral cortex, cerebellar, caudate and larger cerebral white matter and 5th ventricle volumes than insertion carriers or subjects with no variation in this region. Similarly, deletion carriers also demonstrate higher AUD severity scores than insertion carriers or subjects with no variation. The results presented here suggest that copy number variation and in particular the variation at chromosome 11 q14.2 may have an impact in brain volume variation, potentially influencing AUD behavior.
The Mind Research Network, 1101 Yale blvd. NE, Albuquerque, NM 87106, USA. dboutte@mrn.org
David
D
Boutte
Vince D
VD
Calhoun
Jiayu
J
Chen
Amithrupa
A
Sabbineni
Kent
K
Hutchison
Jingyu
J
Liu
D000328:Adult; D019973:Alcohol-Related Disorders / Q000235:genetics* / Q000473:pathology*; D000437:Alcoholism / Q000235:genetics / Q000473:pathology; D001921:Brain / Q000473:pathology*; D002531:Cerebellum / Q000473:pathology; D002540:Cerebral Cortex / Q000473:pathology; D002880:Chromosomes, Human, Pair 11 / Q000235:genetics; D056915:DNA Copy Number Variations; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged