Heritability of the shape of subcortical brain structures in the general population
Gennady V. Roshchupkin (Erasmus MC)
Boris A. Gutman (University of Southern California)
Meike W. Vernooij (Erasmus MC)
Neda Jahanshad (University of Southern California)
Nicholas G. Martin (Queensland Institute of Medical Research)
Albert Hofman (Harvard T.H. Chan School of Public Health, Erasmus MC)
Katie L. McMahon (University of Queensland)
Sven J. Van Der Lee (Erasmus MC)
Cornelia M. van Duijn (Universiteit Leiden, Erasmus MC)
Greig I. De Zubicaray (Queensland University of Technology)
André G. Uitterlinden (Erasmus MC)
Margaret J. Wright (University of Queensland)
Wiro J. Niessen (TU Delft - ImPhys/Quantitative Imaging, Erasmus MC)
Paul M. Thompson (University of Southern California)
M. Arfan Ikram (Erasmus MC)
Hieab H. Adams (Erasmus MC)
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Abstract
The volumes of subcortical brain structures are highly heritable, but genetic underpinnings of their shape remain relatively obscure. Here we determine the relative contribution of genetic factors to individual variation in the shape of seven bilateral subcortical structures: the nucleus accumbens, amygdala, caudate, hippocampus, pallidum, putamen and thalamus. In 3,686 unrelated individuals aged between 45 and 98 years, brain magnetic resonance imaging and genotyping was performed. The maximal heritability of shape varies from 32.7 to 53.3% across the subcortical structures. Genetic contributions to shape extend beyond influences on intracranial volume and the gross volume of the respective structure. The regional variance in heritability was related to the reliability of the measurements, but could not be accounted for by technical factors only. These findings could be replicated in an independent sample of 1,040 twins. Differences in genetic contributions within a single region reveal the value of refined brain maps to appreciate the genetic complexity of brain structures.