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Searching for genetic variants affecting brain connectivity

Wednesday, November 06, 2013 — Poster Session I

4:00 p.m. – 6:00 p.m.

FAES Academic Center (Upper-Level Terrace)

NIAAA

NEURO-43

Authors

  • Z. C. Hommer
  • C. A. Hodgkinson
  • A.A. Rosser
  • E. A. Stein
  • D. Goldman

Abstract

Genotypes at the CHRNA5 locus can predict nicotine craving, success in smoking cessation, and brain connectivity patterns. Recognizing the influence of such genotypes on other neuropathologies and overall neural connectivity, we have performed a genome-wide association study (GWAS) in an attempt to identify genes regulating neural connectivity. BOLD resting state data from 350 subjects were aligned in 3D space and submitted to group independent component analysis (gICA) to identify large-scale brain networks. The 4 networks most relevant to general cognitive capacity were selected based on visual identification and converted to a quantitative phenotype. Subject genotypes spanning the ~730,000 SNPs available in Illumina’s OmniExpress array were analyzed to identify associations between specific genomic loci and the 4 phenotypic networks using PLINK. Analysis yielded a significant association between the default network and a SNP in the CAMTA1 gene, whereas other networks displayed no significant associations with any genomic loci. We generated Q-Q plots to determine whether population admixture was inflating p-values and found no appreciable inflation for the default network. However, association between this factor and CAMTA1 is driven by minor alleles found only in African-American subjects, making it a possible artifact correctable by increases in sample size and/or separation of ethnicities.

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