Genetic Correlations Between Brain Volumes and the WAIS-III Dimensions of Verbal Comprehension, Working Memory, Perceptual Organization, and Processing Speed

Abstract

W e recently showed that the correlation of gray and white matter volume with full scale IQ and the Working Memory dimension are completely mediated by common genetic factors (Posthuma et al., 2002). Here we examine whether the other WAIS III dimensions (Verbal Comprehension, Perceptual Organization, Processing Speed) are also related to gray and white matter volume, and whether any of the dimensions are related to cerebellar volume. Two overlapping samples provided 135 subjects from 60 extended twin families for whom both MRI scans and WAIS III data were available. All three brain volumes are related to Working Memory capacity (r = 0.27). This phenotypic correlation is completely due to a common underlying genetic factor. Processing Speed was genetically related to white matter volume (r g = 0.39). Perceptual Organization was both genetically (r g = 0.39) and environmen-tally (r e = –0.71) related to cerebellar volume. Verbal Two independent studies recently quantified the contribu-tion of genetic and environmental factors to interindividual differences in brain volumes (Baaré et al., 2001; Thompson et al., 2001). Baaré et al. (2001) used magnetic resonance imaging (MRI) to measure intracranial space, total brain volume, total white matter volume, total gray matter volume, and lateral ventricle volume in 258 subjects belonging to 112 (extended) twin families. They reported very high heritabilities for all volumes (ranging from 80 to 90%) except ventricular volume (no genetic influences). Thompson et al. (2001) used voxel based MRI techniques on 10 MZ twin pairs and 10 DZ twin pairs and reported high heritability of gray matter volume in several cortical regions. Results from previous studies also suggested that genetic factors are much more important than environmen-tal factors for inter-individual differences in brain volumes (Bartley et al., 1997; Carmelli et al., 1998; Carmelli et al., 2002; Pennington et al., 2000; Reveley et al., 1984). Since the second half of the 19th century positive corre-lations between head size (as measured with a measuring tape around the head) and psychometric intelligence have been observed. Correlations generally range around 0.20 (Jensen, 1994; Posthuma et al., 2001a), but can be as high as 0.44 (van Valen, 1974). MRI provides a more accurate measure of the size of the brain, as head size includes both brain volume and thickness of the skull. Several studies have correlated MRI-brain volumes with measures of intel-ligence, and, on average, brain volume as measured with MRI and IQ correlate around 0.40 (e.g., Andreasen et al., 1993; Egan et al., 1994; Raz et al., 1993; Storfer, 1999; Wickett et al., 2000; Willerman et al., 1992). Three multivariate genetic studies of brain volume and intelligence have investigated the nature of the correlation between brain volume and intelligence (Pennington et al., 2000; Thompson et al., 2001; Wickett et al., 1997), but did not have the optimal design (Pennington et al., 2000; Wickett et al., 1997) or enough statistical power (Thompson et al., 2001) to decompose the observed corre-lation into genetic and environmental components. Using a dataset consisting of 24 MZ pairs, 31 DZ pairs, and 25 additional siblings (135 individuals from 60 families) for whom both data on brain volume and intelligence were available, we recently showed that the correlations between gray or white matter volume to full scale IQ (WAIS III) and its Working Memory dimension are completely mediated by an underlying set of genes that influences both brain volumes and IQ (Posthuma et al., 2002).