TY - JOUR
T1 - Mapping the Genetic Variation of Regional Brain Volumes as Explained by All Common SNPs from the ADNI Study
AU - Bryant, Christopher
AU - Giovanello, Kelly S.
AU - Ibrahim, Joseph G.
AU - Chang, Jing
AU - Shen, Dinggang
AU - Peterson, Bradley S.
AU - Zhu, Hongtu
N1 - 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.
PY - 2013/8/28
Y1 - 2013/8/28
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=84883193582&partnerID=8YFLogxK
U2 - 10.1371/journal.pone.0071723
DO - 10.1371/journal.pone.0071723
M3 - Article
C2 - 24015190
AN - SCOPUS:84883193582
SN - 1932-6203
VL - 8
JO - PLoS One
JF - PLoS One
IS - 8
M1 - e71723
ER -