Mapping genetic influences on ventricular structure in twins
Source: NeuroImage
2009 Feb;44(4):1312-1323.
Author: Chou YY, Lepore N, Chiang MC, Avedissian C, Barysheva M, McMahon KL, de Zubicaray GI, Meredith M, Wright MJ, Toga AW, Thompson PM PubMed ID: 19041405
Abstract:
Despite substantial progress in measuring the anatomical and functional variability of the human brain, little
is known about the genetic and environmental causes of these variations. Here we developed an automated
system to visualize genetic and environmental effects on brain structure in large brain MRI databases. We
applied our multi-template segmentation approach termed “Multi-Atlas Fluid Image Alignment” to fluidly
propagate hand-labeled parameterized surface meshes, labeling the lateral ventricles, in 3D volumetric MRI
scans of 76 identical (monozygotic, MZ) twins (38 pairs; mean age=24.6 (SD=1.7)); and 56 same-sex
fraternal (dizygotic, DZ) twins (28 pairs; mean age=23.0 (SD=1.8)), scanned as part of a 5-year research study
that will eventually study over 1000 subjects. Mesh surfaces were averaged within subjects to minimize
segmentation error. We fitted quantitative genetic models at each of 30,000 surface points to measure the
proportion of shape variance attributable to (1) genetic differences among subjects, (2) environmental
influences unique to each individual, and (3) shared environmental effects. Surface-based statistical maps,
derived from path analysis, revealed patterns of heritability, and their significance, in 3D. Path coefficients for
the ‘ACE’ model that best fitted the data indicated significant contributions from genetic factors (A=7.3%),
common environment (C=38.9%) and unique environment (E=53.8%) to lateral ventricular volume. Earliermaturing
occipital horn regions may also be more genetically influenced than later-maturing frontal regions.
Maps visualized spatially-varying profiles of environmental versus genetic influences. The approach shows
promise for automatically measuring gene–environment effects in large image databases.