UCL Discovery
UCL home » Library Services » Electronic resources » UCL Discovery

Sex-Dependent Shared and Non-Shared Genetic Architecture Across Mood and Psychotic Disorders

Blokland, G; Grove, J; Chen, C-Y; Cotsapas, C; Tobet, S; Handa, R; St Clair, D; ... The Lundbeck Foundation Initiative for Integrative Psychiatric R; + view all (2021) Sex-Dependent Shared and Non-Shared Genetic Architecture Across Mood and Psychotic Disorders. BioRxiv: Cold Spring Harbor, NY, USA. Green open access

[thumbnail of McQuillin_2020.08.13.249813.full.pdf]
Preview
Text
McQuillin_2020.08.13.249813.full.pdf

Download (1MB) | Preview

Abstract

BACKGROUND: Sex differences in incidence and/or presentation of schizophrenia (SCZ), major depressive disorder (MDD), and bipolar disorder (BIP) are pervasive. Previous evidence for shared genetic risk and sex differences in brain abnormalities across disorders suggest possible shared sex-dependent genetic risk. / METHODS: We conducted the largest to date genome-wide genotype–by–sex (GxS) interaction of risk for these disorders, using 85,735 cases (33,403 SCZ, 19,924 BIP, 32,408 MDD) and 109,946 controls from the Psychiatric Genomics Consortium (PGC) and iPSYCH. / RESULTS: Across disorders, genome-wide significant SNP-by-sex interaction was detected for a locus encompassing NKAIN2 (rs117780815; p=3.2×10−8), that interacts with sodium/potassium-transporting ATPase enzymes implicating neuronal excitability. Three additional loci showed evidence (p<1×10−6) for cross-disorder GxS interaction (rs7302529, p=1.6×10−7; rs73033497, p=8.8×10−7; rs7914279, p=6.4×10−7) implicating various functions. Gene-based analyses identified GxS interaction across disorders (p=8.97×10−7) with transcriptional inhibitor SLTM. Most significant in SCZ was a MOCOS gene locus (rs11665282; p=1.5×10−7), implicating vascular endothelial cells. Secondary analysis of the PGC-SCZ dataset detected an interaction (rs13265509; p=1.1×10−7) in a locus containing IDO2, a kynurenine pathway enzyme with immunoregulatory functions implicated in SCZ, BIP, and MDD. Pathway enrichment analysis detected significant GxS of genes regulating vascular endothelial growth factor (VEGF) receptor signaling in MDD (pFDR<0.05). / CONCLUSIONS: In the largest genome-wide GxS analysis of mood and psychotic disorders to date, there was substantial genetic overlap between the sexes. However, significant sex-dependent effects were enriched for genes related to neuronal development, immune and vascular functions across and within SCZ, BIP, and MDD at the variant, gene, and pathway enrichment levels.

Type: Working / discussion paper
Title: Sex-Dependent Shared and Non-Shared Genetic Architecture Across Mood and Psychotic Disorders
Open access status: An open access version is available from UCL Discovery
DOI: 10.1101/2020.08.13.249813
Publisher version: https://doi.org/10.1101/2020.08.13.249813
Language: English
Additional information: The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY 4.0 International license (http://creativecommons.org/licenses/by/4.0/).
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 Brain Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > Division of Psychiatry
URI: https://discovery.ucl.ac.uk/id/eprint/10136752
Downloads since deposit
11Downloads
Download activity - last month
Download activity - last 12 months
Downloads by country - last 12 months

Archive Staff Only

View Item View Item