Cardiff University | Prifysgol Caerdydd ORCA
Online Research @ Cardiff 
WelshClear Cookie - decide language by browser settings

Polygenic risk for schizophrenia and subcortical brain anatomy in the UK Biobank cohort

Grama, Steluta, Willcocks, Isabella, Hubert, John, Pardiñas, Antonio, Legge, Sophie, Bracher-Smith, Matthew, Menzies, Georgina, Hall, Lynsey, Pocklington, Andrew, Anney, Richard, Bray, Nicholas, Escott-Price, Valentina and Caseras, Xavier 2020. Polygenic risk for schizophrenia and subcortical brain anatomy in the UK Biobank cohort. Translational Psychiatry 10 , 309. 10.1038/s41398-020-00940-0

[img]
Preview
PDF - Published Version
Available under License Creative Commons Attribution.

Download (739kB) | Preview

Abstract

Research has shown differences in subcortical brain volumes between participants with schizophrenia and healthy controls. However, none of these differences have been found to associate with schizophrenia polygenic risk. Here, in a large sample (n = 14,701) of unaffected participants from the UK Biobank, we test whether schizophrenia polygenic risk scores (PRS) limited to specific gene-sets predict subcortical brain volumes. We compare associations with schizophrenia PRS at the whole genome level (‘genomic’, including all SNPs associated with the disorder at a p-value threshold < 0.05) with ‘genic’ PRS (based on SNPs in the vicinity of known genes), ‘intergenic’ PRS (based on the remaining SNPs), and genic PRS limited to SNPs within 7 gene-sets previously found to be enriched for genetic association with schizophrenia (‘abnormal behaviour,’ ‘abnormal long-term potentiation,’ ‘abnormal nervous system electrophysiology,’ ‘FMRP targets,’ ‘5HT2C channels,’ ‘CaV2 channels’ and ‘loss-of-function intolerant genes’). We observe a negative association between the ‘abnormal behaviour’ gene-set PRS and volume of the right thalamus that survived correction for multiple testing (ß = −0.031, pFDR = 0.005) and was robust to different schizophrenia PRS p-value thresholds. In contrast, the only association with genomic PRS surviving correction for multiple testing was for right pallidum, which was observed using a schizophrenia PRS p-value threshold < 0.01 (ß = −0.032, p = 0.0003, pFDR = 0.02), but not when using other PRS P-value thresholds. We conclude that schizophrenia PRS limited to functional gene sets may provide a better means of capturing differences in subcortical brain volume than whole genome PRS approaches.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Medicine
MRC Centre for Neuropsychiatric Genetics and Genomics (CNGG)
Cardiff University Brain Research Imaging Centre (CUBRIC)
Publisher: Springer Nature
ISSN: 2158-3188
Funders: MRC
Date of First Compliant Deposit: 21 July 2020
Date of Acceptance: 14 July 2020
Last Modified: 16 Oct 2020 10:41
URI: http://orca-mwe.cf.ac.uk/id/eprint/133569

Actions (repository staff only)

Edit Item Edit Item

Downloads

Downloads per month over past year

View more statistics