Heritability of the shape of subcortical brain structures in the general population

Gennady V. Roshchupkin; Boris A. Gutman; Meike W. Vernooij; Neda Jahanshad; Nicholas G. Martin; Albert Hofman; Katie L. McMahon; Sven J. Van Der Lee; Cornelia M. van Duijn; Greig I. De Zubicaray; André G. Uitterlinden; Margaret J. Wright; Wiro J. Niessen; Paul M. Thompson; M. Arfan Ikram; Hieab H. Adams

doi:10.1038/ncomms13738

Heritability of the shape of subcortical brain structures in the general population

Gennady V. Roshchupkin, Boris A. Gutman, Meike W. Vernooij, Neda Jahanshad, Nicholas G. Martin, Albert Hofman, Katie L. McMahon, Sven J. Van Der Lee, Cornelia M. van Duijn, Greig I. De Zubicaray, André G. Uitterlinden, Margaret J. Wright, Wiro J. Niessen, Paul M. Thompson, M. Arfan Ikram^*, Hieab H. Adams

^*Corresponding author for this work

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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.

Original language	English
Article number	13738
Journal	Nature Communications
Volume	7
DOIs	https://doi.org/10.1038/ncomms13738
Publication status	Published - 15 Dec 2016

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Roshchupkin, G. V., Gutman, B. A., Vernooij, M. W., Jahanshad, N., Martin, N. G., Hofman, A., McMahon, K. L., Van Der Lee, S. J., van Duijn, C. M., De Zubicaray, G. I., Uitterlinden, A. G., Wright, M. J., Niessen, W. J., Thompson, P. M., Ikram, M. A., & Adams, H. H. (2016). Heritability of the shape of subcortical brain structures in the general population. Nature Communications, 7, Article 13738. https://doi.org/10.1038/ncomms13738

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title = "Heritability of the shape of subcortical brain structures in the general population",

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.",

author = "Roshchupkin, {Gennady V.} and Gutman, {Boris A.} and Vernooij, {Meike W.} and Neda Jahanshad and Martin, {Nicholas G.} and Albert Hofman and McMahon, {Katie L.} and {Van Der Lee}, {Sven J.} and {van Duijn}, {Cornelia M.} and {De Zubicaray}, {Greig I.} and Uitterlinden, {Andr{\'e} G.} and Wright, {Margaret J.} and Niessen, {Wiro J.} and Thompson, {Paul M.} and Ikram, {M. Arfan} and Adams, {Hieab H.}",

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Roshchupkin, GV, Gutman, BA, Vernooij, MW, Jahanshad, N, Martin, NG, Hofman, A, McMahon, KL, Van Der Lee, SJ, van Duijn, CM, De Zubicaray, GI, Uitterlinden, AG, Wright, MJ, Niessen, WJ, Thompson, PM, Ikram, MA & Adams, HH 2016, 'Heritability of the shape of subcortical brain structures in the general population', Nature Communications, vol. 7, 13738. https://doi.org/10.1038/ncomms13738

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AU - Roshchupkin, Gennady V.

AU - Gutman, Boris A.

AU - Vernooij, Meike W.

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AU - Martin, Nicholas G.

AU - Hofman, Albert

AU - McMahon, Katie L.

AU - Van Der Lee, Sven J.

AU - van Duijn, Cornelia M.

AU - De Zubicaray, Greig I.

AU - Uitterlinden, André G.

AU - Wright, Margaret J.

AU - Niessen, Wiro J.

AU - Thompson, Paul M.

AU - Ikram, M. Arfan

AU - Adams, Hieab H.

PY - 2016/12/15

Y1 - 2016/12/15

N2 - 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.

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Heritability of the shape of subcortical brain structures in the general population

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