title: A comparison of heritability maps of cortical surface area and thickness and the influence of adjustment for whole brain measures: a magnetic resonance imaging twin study.
abstract: Understanding the genetic and environmental contributions to measures of brain structure such as surface area and cortical thickness is important for a better understanding of the nature of brain-behavior relationships and changes due to development or disease. Continuous spatial maps of genetic influences on these structural features can contribute to our understanding of regional patterns of heritability, since it remains to be seen whether genetic contributions to brain structure respect the boundaries of any traditional parcellation approaches. Using data from magnetic resonance imaging scans collected on a large sample of monozygotic and dizygotic twins in the Vietnam Era Twin Study of Aging, we created maps of the heritability of areal expansion (a vertex-based area measure) and cortical thickness and examined the degree to which these maps were affected by adjustment for total surface area and mean cortical thickness. We also compared the approach of estimating regional heritability based on the average heritability of vertices within the region to the more traditional region-of-interest (ROI)-based approach. The results suggested high heritability across the cortex for areal expansion and, to a slightly lesser degree, for cortical thickness. There was a great deal of genetic overlap between global and regional measures for surface area, so maps of region-specific genetic influences on surface area revealed more modest heritabilities. There was greater inter-regional variability in heritabilities when calculated using the traditional ROI-based approach compared to summarizing vertex-by-vertex heritabilities within regions. Discrepancies between the approaches were greatest in small regions and tended to be larger for surface area than for cortical thickness measures. Implications regarding brain phenotypes for future genetic association studies are discussed.
authors.affiliation: Department of Psychiatry, University of California San Diego, La Jolla, CA, USA. lteyler@ucsd.edu
authors.forename: Lisa T
authors.initials: LT
authors.lastname: Eyler
authors.forename: Chi-Hua
authors.initials: CH
authors.lastname: Chen
authors.forename: Matthew S
authors.initials: MS
authors.lastname: Panizzon
authors.forename: Christine
authors.initials: C
authors.lastname: Fennema-Notestine
authors.forename: Michael C
authors.initials: MC
authors.lastname: Neale
authors.forename: Amy
authors.initials: A
authors.lastname: Jak
authors.forename: Terry L
authors.initials: TL
authors.lastname: Jernigan
authors.forename: Bruce
authors.initials: B
authors.lastname: Fischl
authors.forename: Carol E
authors.initials: CE
authors.lastname: Franz
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Lyons
authors.forename: Michael
authors.initials: M
authors.lastname: Grant
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Prom-Wormley
authors.forename: Larry J
authors.initials: LJ
authors.lastname: Seidman
authors.forename: Ming T
authors.initials: MT
authors.lastname: Tsuang
authors.forename: Mark Joseph A
authors.initials: MJ
authors.lastname: Fiecas
authors.forename: Anders M
authors.initials: AM
authors.lastname: Dale
authors.forename: William S
authors.initials: WS
authors.lastname: Kremen
mesh_terms: D001921:Brain / Q000033:anatomy & histology; D001931:Brain Mapping; D002540:Cerebral Cortex / Q000033:anatomy & histology*; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009929:Organ Size / Q000235:genetics; D019655:Quantitative Trait, Heritable; D014427:Twins / Q000235:genetics*