title: Predicting white matter integrity from multiple common genetic variants.
abstract: Several common genetic variants have recently been discovered that appear to influence white matter microstructure, as measured by diffusion tensor imaging (DTI). Each genetic variant explains only a small proportion of the variance in brain microstructure, so we set out to explore their combined effect on the white matter integrity of the corpus callosum. We measured six common candidate single-nucleotide polymorphisms (SNPs) in the COMT, NTRK1, BDNF, ErbB4, CLU, and HFE genes, and investigated their individual and aggregate effects on white matter structure in 395 healthy adult twins and siblings (age: 20-30 years). All subjects were scanned with 4-tesla 94-direction high angular resolution diffusion imaging. When combined using mixed-effects linear regression, a joint model based on five of the candidate SNPs (COMT, NTRK1, ErbB4, CLU, and HFE) explained ≈ 6% of the variance in the average fractional anisotropy (FA) of the corpus callosum. This predictive model had detectable effects on FA at 82% of the corpus callosum voxels, including the genu, body, and splenium. Predicting the brain's fiber microstructure from genotypes may ultimately help in early risk assessment, and eventually, in personalized treatment for neuropsychiatric disorders in which brain integrity and connectivity are affected.
authors.affiliation: Laboratory of Neuro Imaging, Department of Neurology, UCLA School of Medicine, Los Angeles, CA 90095-1769, USA.
authors.forename: Omid
authors.initials: O
authors.lastname: Kohannim
authors.forename: Neda
authors.initials: N
authors.lastname: Jahanshad
authors.forename: Meredith N
authors.initials: MN
authors.lastname: Braskie
authors.forename: Jason L
authors.initials: JL
authors.lastname: Stein
authors.forename: Ming-Chang
authors.initials: MC
authors.lastname: Chiang
authors.forename: April H
authors.initials: AH
authors.lastname: Reese
authors.forename: Derrek P
authors.initials: DP
authors.lastname: Hibar
authors.forename: Arthur W
authors.initials: AW
authors.lastname: Toga
authors.forename: Katie L
authors.initials: KL
authors.lastname: McMahon
authors.forename: Greig I
authors.initials: GI
authors.lastname: de Zubicaray
authors.forename: Sarah E
authors.initials: SE
authors.lastname: Medland
authors.forename: Grant W
authors.initials: GW
authors.lastname: Montgomery
authors.forename: Nicholas G
authors.initials: NG
authors.lastname: Martin
authors.forename: Margaret J
authors.initials: MJ
authors.lastname: Wright
authors.forename: Paul M
authors.initials: PM
authors.lastname: Thompson
mesh_terms: D000328:Adult; D015331:Cohort Studies; D003337:Corpus Callosum / Q000378:metabolism / Q000473:pathology* / Q000502:physiology; D056324:Diffusion Tensor Imaging / Q000379:methods; D005260:Female; D014644:Genetic Variation / Q000235:genetics*; D006801:Humans; D008297:Male; D009413:Nerve Fibers, Myelinated / Q000473:pathology / Q000502:physiology; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011237:Predictive Value of Tests; D055815:Young Adult