A genome-wide association study identifies genetic loci associated with specific lobar brain volumes

Commun Biol. 2019 Aug 2:2:285. doi: 10.1038/s42003-019-0537-9. eCollection 2019.


Brain lobar volumes are heritable but genetic studies are limited. We performed genome-wide association studies of frontal, occipital, parietal and temporal lobe volumes in 16,016 individuals, and replicated our findings in 8,789 individuals. We identified six genetic loci associated with specific lobar volumes independent of intracranial volume. Two loci, associated with occipital (6q22.32) and temporal lobe volume (12q14.3), were previously reported to associate with intracranial and hippocampal volume, respectively. We identified four loci previously unknown to affect brain volumes: 3q24 for parietal lobe volume, and 1q22, 4p16.3 and 14q23.1 for occipital lobe volume. The associated variants were located in regions enriched for histone modifications (DAAM1 and THBS3), or close to genes causing Mendelian brain-related diseases (ZIC4 and FGFRL1). No genetic overlap between lobar volumes and neurological or psychiatric diseases was observed. Our findings reveal part of the complex genetics underlying brain development and suggest a role for regulatory regions in determining brain volumes.

Keywords: Biomarkers; Genome-wide association studies; Neurology.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural
  • Research Support, N.I.H., Intramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Frontal Lobe / diagnostic imaging
  • Frontal Lobe / growth & development*
  • Gene Expression Regulation, Developmental
  • Genetic Loci*
  • Genetic Variation*
  • Genome-Wide Association Study
  • Genotype
  • Heredity
  • Humans
  • Magnetic Resonance Imaging
  • Occipital Lobe / diagnostic imaging
  • Occipital Lobe / growth & development*
  • Organ Size / genetics
  • Parietal Lobe / diagnostic imaging
  • Parietal Lobe / growth & development*
  • Phenotype
  • Temporal Lobe / drug effects
  • Temporal Lobe / growth & development*
  • United Kingdom

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