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Thirty-Third Annual Meeting of the Society for Research in Psychopathology

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Shared genetic contributions to cognition and psychiatric disorder risk based on genome-wide data from 150,000 participants

Differences in cognitive performance are consistently related to risk for neuropsychiatric disorders. Here, we estimated the genetic correlation between measures of cognitive performance and risk for major neuropsychiatric disorders. Participants were European-ancestry customers of the personal genetics company 23andMe, Inc., age 50-85 who were genotyped, consented to participate in research and completed online tests of crystallized (vocabulary, N = 187,672) and/or fluid cognitive ability (change detection, N = 159,003; digit-symbol matching, N = 132,667). GWAS were conducted for each cognitive test and genetic correlation was calculated using LD score regression between cognitive performance and psychiatric disorders (based on recent PGC GWAS meta-analyses). Schizophrenia had moderate genetic correlations with fluid cognition (visual change detection rg = -0.27, p < 9.2e-24; digit-symbol matching rg = -0.26, p < 5.2e-27), but was only somewhat associated with vocabulary scores (rg = -0.07, p < 0.004). Autism, however, showed a robust genetic correlation with vocabulary (rg = 0.30, p < 5.6e-13) and little to no genetic correlation with fluid cognition (rg’s < 0.08, p’s > 0.005). These findings suggest neuropsychiatric genetic risk for is differently associated with crystallized vs fluid cognitive ability, providing insights into neuropsychiatric risk architecture based on commonly occurring genetic variants.

Roger Strong
McLean Hospital and Harvard Medical School

Caitlin Carey
Broad Institute

Yunru Huang

23andMe Research Team

Stella Aslibekyan

Jordan Smoller
Massachusetts General Hospital and Harvard Medical School

Jeremy Wilmer
Wellesley College

Elise Robinson
Broad Institute and Harvard School of Public Health

Laura Germine


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