Genome-wide autozygosity is associated with lower general cognitive ability

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.