Polygenic risk score for schizophrenia is more strongly associated with ancestry than with schizophrenia
Year: 2018
Type: article
Abstract: BACKGROUND: The polygenic risk score (PRS) for schizophrenia, derived from very large numbers of weakly associated genetic markers, has been repeatedly shown to be robustly associated with schizophrenia in independent samples and also with other diseases and traits. AIM: This study aims to explore the distribution of the schizophrenia PRS in subjects of different ancestry. METHODS: The schizophrenia PRS derived from the large genome-wide association study carried out by the Psychiatric Genetics Consortium was calculated using the downloaded genotypes of HapMap subjects from 11 different ancestral groups. It was also calculated using downloaded genotypes of European schizophrenia cases and controls from the CommonMind Consortium. RESULTS: The PRS for schizophrenia varied significantly between ancestral groups (P<2×10(-16)) and was much higher in African than European HapMap subjects. The mean difference between these groups was 10 times as high as the mean difference between European schizophrenia cases and controls. The distributions of scores for African and European subjects hardly overlapped. CONCLUSION: The PRS cannot be regarded as simply a measure of the polygenic contribution to risk of schizophrenia and clearly contains a strong ancestry component. It is possible that this could be controlled to some extent by incorporating principal components as covariates, but doubts remain as to how it should be interpreted. The PRS derived from European subjects cannot be applied to non-Europeans, limiting its potential usefulness in clinical settings and raising issues of inequity in health provision. Previous studies that have used the PRS should be re-examined in the light of these findings.
Source: Psychiatric Genetics
Author: David Curtis
Institutions: Queen Mary University of London, University College London
Language: English
Subfield: Genetics
Domain: Life Sciences
Open Access status: green
Awards: Inhibition, Oscillations and Information Processing in Schizophrenia, G1226976794, Developmental Trajectories of Negative Symptoms in Schizophrenia, G1342218999, G148749253, Identifying therapeutic targets for autism using Shank3-deficient mice, G2182537161, G2946751114, White Matter Abnormalities in Schizophrenia, G37153953, G4126499158, G4225100588, Src hypoactivity as a mediator of various molecular alterations leading to NMDAR, International Cohort Collection for Bipolar Disorder, Genetics Association in Schizophrenia and Other Disorders, G4867329959, G5115457503, 1/3-Networks from Multidimensional Data for Schizophrenia and Related Disorders, Plasma and CSF Abeta peptides in late-onset major depression, G7095773877, Neurobehavioral Bases of Emotion Regulation and Dysregulation in Adolescence, G8413678899, G9000064556, G9000174724
OpenAlex ID: W2952727348