- Home
- About
- Collaborative Data Access (SAGs)
- Publications
- For Members
Title | Genome-wide association identifies genetic variants associated with lentiform nucleus volume in N = 1345 young and elderly subjects. |
Publication Type | Journal Article |
Year of Publication | 2013 |
Authors | Hibar DP, Stein JL, Ryles AB, Kohannim O, Jahanshad N, Medland SE, Hansell NK, McMahon KL, de Zubicaray GI, Montgomery GW, Martin NG, Wright MJ, Saykin AJ, Jack CR, Weiner MW, Toga AW, Thompson PM |
Corporate Authors | Alzheimer’s Disease Neuroimaging Initiative |
Journal | Brain Imaging Behav |
Volume | 7 |
Issue | 2 |
Pagination | 102-15 |
Date Published | 06/2013 |
ISSN | 1931-7565 |
Keywords | Adult, Aged, Aged, 80 and over, Alzheimer Disease, Cognitive Dysfunction, Corpus Striatum, Female, Genetic Predisposition to Disease, Genetic Variation, Genome-Wide Association Study, Genotype, Humans, Longitudinal Studies, Male, Polymorphism, Single Nucleotide, Young Adult |
Abstract | Deficits in lentiform nucleus volume and morphometry are implicated in a number of genetically influenced disorders, including Parkinson's disease, schizophrenia, and ADHD. Here we performed genome-wide searches to discover common genetic variants associated with differences in lentiform nucleus volume in human populations. We assessed structural MRI scans of the brain in two large genotyped samples: the Alzheimer's Disease Neuroimaging Initiative (ADNI; N = 706) and the Queensland Twin Imaging Study (QTIM; N = 639). Statistics of association from each cohort were combined meta-analytically using a fixed-effects model to boost power and to reduce the prevalence of false positive findings. We identified a number of associations in and around the flavin-containing monooxygenase (FMO) gene cluster. The most highly associated SNP, rs1795240, was located in the FMO3 gene; after meta-analysis, it showed genome-wide significant evidence of association with lentiform nucleus volume (P MA = 4.79 × 10(-8)). This commonly-carried genetic variant accounted for 2.68 % and 0.84 % of the trait variability in the ADNI and QTIM samples, respectively, even though the QTIM sample was on average 50 years younger. Pathway enrichment analysis revealed significant contributions of this gene to the cytochrome P450 pathway, which is involved in metabolizing numerous therapeutic drugs for pain, seizures, mania, depression, anxiety, and psychosis. The genetic variants we identified provide replicated, genome-wide significant evidence for the FMO gene cluster's involvement in lentiform nucleus volume differences in human populations. |
DOI | 10.1007/s11682-012-9199-7 |
Alternate Journal | Brain Imaging Behav |
PubMed ID | 22903471 |
PubMed Central ID | PMC3779070 |
Grant List | K01 AG030514 / AG / NIA NIH HHS / United States T15 LM007356 / LM / NLM NIH HHS / United States EB007813 / EB / NIBIB NIH HHS / United States R01 EB007813 / EB / NIBIB NIH HHS / United States R01 AG019771 / AG / NIA NIH HHS / United States AG016570 / AG / NIA NIH HHS / United States P30 AG10133 / AG / NIA NIH HHS / United States F30 AG041681 / AG / NIA NIH HHS / United States P30 AG010133 / AG / NIA NIH HHS / United States T32 GM008042 / GM / NIGMS NIH HHS / United States U24 AG021886 / AG / NIA NIH HHS / United States R01 AG040060 / AG / NIA NIH HHS / United States R21 RR019771 / RR / NCRR NIH HHS / United States R01 LM005639 / LM / NLM NIH HHS / United States U01 AG032984 / AG / NIA NIH HHS / United States U01 AG024904 / AG / NIA NIH HHS / United States U19 AG010483 / AG / NIA NIH HHS / United States EB01651 / EB / NIBIB NIH HHS / United States EB008432 / EB / NIBIB NIH HHS / United States RR019771 / RR / NCRR NIH HHS / United States P50 AG016570 / AG / NIA NIH HHS / United States R01 HD050735 / HD / NICHD NIH HHS / United States R01 EB008432 / EB / NIBIB NIH HHS / United States R01 AG19771 / AG / NIA NIH HHS / United States F30AG041681 / AG / NIA NIH HHS / United States EB008281 / EB / NIBIB NIH HHS / United States LM05639 / LM / NLM NIH HHS / United States T15 LM07356 / LM / NLM NIH HHS / United States P30 AG010129 / AG / NIA NIH HHS / United States R01 EB008281 / EB / NIBIB NIH HHS / United States |