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Genome-wide autozygosity is associated with lower general cognitive ability.

D P Howrigan1,2, M A Simonson3, G Davies4

  • 1Analytic and Translational Genetics Unit, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.

Molecular Psychiatry
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Summary

Inbreeding depression, indicated by autozygosity, is linked to lower cognitive ability. This study found that increased autozygosity predicts reduced general cognitive ability in European ancestry individuals.

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Area of Science:

  • Genetics
  • Human Evolution
  • Cognitive Neuroscience

Background:

  • Inbreeding depression, reduced fitness from related parents, arises from autozygosity exposing deleterious mutations.
  • Autozygosity, identical chromosomal segments, can occur even in outbred populations due to cryptic relatedness.
  • Understanding autozygosity's impact on traits like cognitive ability is crucial for evolutionary and genetic studies.

Purpose of the Study:

  • To investigate the association between genome-wide autozygosity and general cognitive ability.
  • To quantify the effect of autozygosity on cognitive performance in a large, unselected sample.
  • To explore the characteristics of autozygous tracts (length, frequency) associated with cognitive ability.

Main Methods:

  • Utilized dense genome-wide single-nucleotide polymorphism (SNP) data from 4854 European ancestry participants.
  • Estimated autozygosity using runs of homozygosity (ROH) to identify autozygous tracts across the genome.
  • Performed association mapping to identify specific genomic regions linked to autozygosity and cognitive ability.

Main Results:

  • Increased levels of autozygosity were significantly associated with lower general cognitive ability.
  • An estimated 0.6 standard deviation drop in cognitive ability was observed among offspring of first cousins.
  • Longer and rarer autozygous tracts showed a stronger association with reduced cognitive ability, aligning with theoretical predictions.

Conclusions:

  • Autozygosity plays a role in determining general cognitive ability, likely through the action of recessive or partially recessive deleterious alleles.
  • These findings suggest that alleles negatively impacting cognitive ability have been under negative selection throughout human evolution.
  • The study provides empirical evidence supporting the genetic underpinnings of cognitive ability and the impact of inbreeding depression.