Polygenic Scores for Cognitive Abilities and Their Association with Different Aspects of General Intelligence-A Deep Phenotyping Approach

Mol Neurobiol. 2021 Aug;58(8):4145-4156. doi: 10.1007/s12035-021-02398-7. Epub 2021 May 5.

Abstract

Intelligence is a highly polygenic trait and genome-wide association studies (GWAS) have identified thousands of DNA variants contributing with small effects. Polygenic scores (PGS) can aggregate those effects for trait prediction in independent samples. As large-scale light-phenotyping GWAS operationalized intelligence as performance in rather superficial tests, the question arises which intelligence facets are actually captured. We used deep-phenotyping to investigate the molecular determinants of individual differences in cognitive ability. We, therefore, studied the association between PGS of intelligence (IQ-PGS), cognitive performance (CP-PGS), and educational attainment (EA-PGS) with a wide range of intelligence facets in a sample of 557 healthy adults. IQ-PGS, CP-PGS, and EA-PGS had the highest incremental R2s for general (2.71%; 4.27%; 2.06%), verbal (3.30%; 4.64%; 1.61%), and numerical intelligence (3.06%; 3.24%; 1.26%) and the weakest for non-verbal intelligence (0.89%; 1.47%; 0.70%) and memory (0.80%; 1.06%; 0.67%). These results indicate that PGS derived from light-phenotyping GWAS do not reflect different facets of intelligence equally well, and thus should not be interpreted as genetic indicators of intelligence per se. The findings refine our understanding of how PGS are related to other traits or life outcomes.

Keywords: Cognitive abilities; Cognitive performance; Deep-phenotyping; Educational attainment; Intelligence; Polygenic scores.

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Cognition / physiology*
  • Female
  • Genome-Wide Association Study / methods*
  • Humans
  • Intelligence / genetics*
  • Male
  • Mental Status and Dementia Tests*
  • Middle Aged
  • Multifactorial Inheritance / genetics*
  • Phenotype*
  • Young Adult