A single nucleotide polymorphism associated with reduced alcohol intake in the RASGRF2 gene predicts larger cortical volumes but faster longitudinal ventricular expansion in the elderly

Florence F. Roussotte, Boris A. Gutman, Derrek P. Hibar, Neda Jahanshad, Sarah K. Madsen, Clifford R Jr. Jack, Michael W. Weiner, Paul M. Thompson

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

A recent genome-wide association meta-analysis showed a suggestive association between alcohol intake in humans and a common single nucleotide polymorphism in the ras-specific guanine nucleotide releasing factor 2 gene. Here, we tested whether this variant - associated with lower alcohol consumption - showed associations with brain structure and longitudinal ventricular expansion over time, across two independent elderly cohorts, totaling 1,032 subjects. We first examined a large sample of 738 elderly participants with neuroimaging and genetic data from the Alzheimer's Disease Neuroimaging Initiative (ADNI1). Then, we assessed the generalizability of the findings by testing this polymorphism in a replication sample of 294 elderly subjects from a continuation of the first ADNI project (ADNI2) to minimize the risk of reporting false positive results. The minor allele - previously linked with lower alcohol intake - was associated with larger volumes in various cortical regions, notably the medial prefrontal cortex and cingulate gyrus in both cohorts. Intriguingly, the same allele also predicted faster ventricular expansion rates in the ADNI1 cohort at 1-and 2-year follow up. Despite a lack of alcohol consumption data in this study cohort, these findings, combined with earlier functional imaging investigations of the same gene, suggest the existence of reciprocal interactions between genes, brain, and drinking behavior.

Original languageEnglish (US)
Article numberArticle 93
JournalFrontiers in Aging Neuroscience
Volume5
Issue numberDEC
DOIs
StatePublished - 2013

Fingerprint

Single Nucleotide Polymorphism
Alcohols
Neuroimaging
Alcohol Drinking
Guanine Nucleotide-Releasing Factor 2
ras-GRF1
Alleles
Genes
Drinking Behavior
Genome-Wide Association Study
Gyrus Cinguli
Brain
Prefrontal Cortex
Meta-Analysis
Alzheimer Disease
Cohort Studies

Keywords

  • Aging neuroscience
  • Brain volume
  • Neuroimaging genetics
  • Rasgrf2
  • Structural MRI
  • Ventricular expansion

ASJC Scopus subject areas

  • Aging
  • Cognitive Neuroscience

Cite this

A single nucleotide polymorphism associated with reduced alcohol intake in the RASGRF2 gene predicts larger cortical volumes but faster longitudinal ventricular expansion in the elderly. / Roussotte, Florence F.; Gutman, Boris A.; Hibar, Derrek P.; Jahanshad, Neda; Madsen, Sarah K.; Jack, Clifford R Jr.; Weiner, Michael W.; Thompson, Paul M.

In: Frontiers in Aging Neuroscience, Vol. 5, No. DEC, Article 93, 2013.

Research output: Contribution to journalArticle

Roussotte, Florence F. ; Gutman, Boris A. ; Hibar, Derrek P. ; Jahanshad, Neda ; Madsen, Sarah K. ; Jack, Clifford R Jr. ; Weiner, Michael W. ; Thompson, Paul M. / A single nucleotide polymorphism associated with reduced alcohol intake in the RASGRF2 gene predicts larger cortical volumes but faster longitudinal ventricular expansion in the elderly. In: Frontiers in Aging Neuroscience. 2013 ; Vol. 5, No. DEC.
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