Curtis, D;
(2018)
Polygenic risk score for schizophrenia is more strongly associated with ancestry than with schizophrenia.
Psychiatric Genetics
, 28
(5)
pp. 85-89.
10.1097/YPG.0000000000000206.
Preview |
Text
Curtis PRShapmap.250518.pdf - Accepted Version Download (310kB) | Preview |
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.
| Type: | Article |
|---|---|
| Title: | Polygenic risk score for schizophrenia is more strongly associated with ancestry than with schizophrenia |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1097/YPG.0000000000000206 |
| Publisher version: | https://doi.org/10.1097/YPG.0000000000000206 |
| Language: | English |
| Additional information: | This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions. |
| Keywords: | Science & Technology, Life Sciences & Biomedicine, Genetics & Heredity, Neurosciences, Neurosciences & Neurology, expression, polygenic risk score, RNA, schizophrenia, POPULATIONS, COMMON, PLINK |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences > Genetics, Evolution and Environment |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10065027 |
Archive Staff Only
 |
View Item |
