Handedness and its genetic influences are associated with structural asymmetries of the cerebral cortex in 31,864 individuals

Proc Natl Acad Sci U S A. 2021 Nov 23;118(47):e2113095118. doi: 10.1073/pnas.2113095118.


Roughly 10% of the human population is left-handed, and this rate is increased in some brain-related disorders. The neuroanatomical correlates of hand preference have remained equivocal. We resampled structural brain image data from 28,802 right-handers and 3,062 left-handers (UK Biobank population dataset) to a symmetrical surface template, and mapped asymmetries for each of 8,681 vertices across the cerebral cortex in each individual. Left-handers compared to right-handers showed average differences of surface area asymmetry within the fusiform cortex, the anterior insula, the anterior middle cingulate cortex, and the precentral cortex. Meta-analyzed functional imaging data implicated these regions in executive functions and language. Polygenic disposition to left-handedness was associated with two of these regional asymmetries, and 18 loci previously linked with left-handedness by genome-wide screening showed associations with one or more of these asymmetries. Implicated genes included six encoding microtubule-related proteins: TUBB, TUBA1B, TUBB3, TUBB4A, MAP2, and NME7-mutations in the latter can cause left to right reversal of the visceral organs. There were also two cortical regions where average thickness asymmetry was altered in left-handedness: on the postcentral gyrus and the inferior occipital cortex, functionally annotated with hand sensorimotor and visual roles. These cortical thickness asymmetries were not heritable. Heritable surface area asymmetries of language-related regions may link the etiologies of hand preference and language, whereas nonheritable asymmetries of sensorimotor cortex may manifest as consequences of hand preference.

Keywords: brain asymmetry; cerebral cortex; gene–brain–behavior; left-handedness; polygenic scores.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Behavior / physiology
  • Biological Specimen Banks
  • Brain / diagnostic imaging
  • Brain / physiology
  • Brain Mapping
  • Cerebral Cortex / diagnostic imaging
  • Cerebral Cortex / physiology*
  • Female
  • Functional Laterality / genetics*
  • Functional Laterality / physiology*
  • Hand
  • Humans
  • Language
  • Magnetic Resonance Imaging
  • Male
  • Middle Aged
  • Occipital Lobe
  • Sensorimotor Cortex