Mapping the Genetic Variation of Regional Brain Volumes as Explained by All Common SNPs from the ADNI Study

Christopher Bryant, Kelly S. Giovanello, Joseph G. Ibrahim, Jing Chang, Dinggang Shen, Bradley S. Peterson, Hongtu Zhu

Research output: Contribution to journalArticlepeer-review

23 Citations (Scopus)

Abstract

Typically twin studies are used to investigate the aggregate effects of genetic and environmental influences on brain phenotypic measures. Although some phenotypic measures are highly heritable in twin studies, SNPs (single nucleotide polymorphisms) identified by genome-wide association studies (GWAS) account for only a small fraction of the heritability of these measures. We mapped the genetic variation (the proportion of phenotypic variance explained by variation among SNPs) of volumes of pre-defined regions across the whole brain, as explained by 512,905 SNPs genotyped on 747 adult participants from the Alzheimer's Disease Neuroimaging Initiative (ADNI). We found that 85% of the variance of intracranial volume (ICV) (p = 0.04) was explained by considering all SNPs simultaneously, and after adjusting for ICV, total grey matter (GM) and white matter (WM) volumes had genetic variation estimates near zero (p = 0.5). We found varying estimates of genetic variation across 93 non-overlapping regions, with asymmetry in estimates between the left and right cerebral hemispheres. Several regions reported in previous studies to be related to Alzheimer's disease progression were estimated to have a large proportion of volumetric variance explained by the SNPs.

Original languageEnglish
Article numbere71723
JournalPloS one
Volume8
Issue number8
DOIs
Publication statusPublished - 2013 Aug 28

Bibliographical note

Funding Information:
Data collection and sharing for this project was funded by the Alzheimer's Disease Neuroimaging Initiative (ADNI), which includes funds from commercial sources (Abbott, Amorfix Life Sciences Ltd.; AstraZeneca; Bayer HealthCare; BioClinica, Inc.; Biogen Idec Inc.; Bristol-Myers Squibb Company; Eisai Inc.; Elan Pharmaceuticals Inc.; Eli Lilly and Company; F. Hoffmann-La Roche Ltd and its affiliated company Genentech, Inc.; GE Healthcare; Innogenetics, N.V.; IXICO Ltd.; Janssen Alzheimer Immunotherapy Research & Development, LLC.; Johnson & Johnson Pharmaceutical Research & Development LLC.; Medpace, Inc.; Merck & Co., Inc.; Meso Scale Diagnostics, LLC.; Novartis Pharmaceuticals Corporation; Pfizer Inc.; Servier; Synarc Inc.; and Takeda Pharmaceutical Company). This does not alter the authors' adherence to all the PLOS ONE policies on sharing data and materials.

ASJC Scopus subject areas

  • General Biochemistry,Genetics and Molecular Biology
  • General Agricultural and Biological Sciences
  • General

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