A population-based study of shared genetic variation between premorbid IQ and psychosis among male twin pairs and sibling pairs from Sweden

Abstract

Context: The strong association between lower IQ and risk for psychosis has led to the suggestion that the search for genes influencing cognition may provide a useful strategy for examining the genetic origins of psychosis. However, research in this area has generally used designs in which twin pairs are selected by case status and with assessment of IQ after the onset of psychosis rather than longitudinal population-based samples. Objective: To examine the relationship and shared genetic origin between premorbid IQ and psychotic disorders in a longitudinal population-based cohort. Design: Genetically informative longitudinal study. Setting: Population-based cohort in Sweden. Participants: Individuals were identified from the populationbased Swedish Multi-Generation Register and consisted of male sibling (n=369 960), monozygotic twin (n=1986), and dizygotic twin (n=2253) pairs born between January 1951 and December 1976. Their IQs were measured during compulsory military conscription. Main Outcome Measure: Individuals having a subsequent diagnosis of psychosis were identified via the Swedish National Hospital Discharge Register. Results: Heritability estimates for IQ and psychosis were similar to previous estimates, approximately 69% and 56%, respectively. However, the phenotypic correlation between IQ and psychosis was only-0.11, of which 91% was due to shared genetic influences. The proportion of genetic variance for psychosis shared with that for IQwas approximately 7%. Conclusions: Using IQ as a phenotype to identify genes that have an important role in the genetic origin of schizophrenia is unlikely to be a successful strategy. The low correlation seen in this study between premorbid IQ and psychosis vs the higher correlations reported in the literature with postmorbid IQ suggests the correlation between these phenotypes has more to do with the influence that the onset of psychosis has on cognitive functioning than with shared genetic origin. © 2012 American Medical Association.