Archival ReportCirculating Proteins Influencing Psychiatric Disease: A Mendelian Randomization Study
Section snippets
Proteomic Studies
The association between circulating protein levels and genetic variants was assessed in 6 large-scale genome-wide proteomic studies: the Fenland Study (10), the Framingham Heart Study (FHS) (12), the IMPROVE study (11), the INTERVAL study (13), the AGES-Reykjavik study (15), and the KORA F4 study (14). These studies were based on populations predominantly of European ancestries. The Fenland, INTERVAL, AGES, and KORA F4 studies used slow off-rate modified aptamer (SOMAmer)-based SomaLogic
Estimated Potential Causal Effects of Circulating Protein Levels on Psychiatric Disorders
An overview of this two-sample MR is presented in Figure 1. Cis-pQTLs or their LD proxies for circulating proteins profiled in 6 large-scale proteomic studies (10, 11, 12, 13, 14, 15) were selected as genetic instruments. After data harmonization, 1611 proteins or complexes had valid genetic instruments that could be tested in at least 1 of the 10 psychiatric disorder GWASs (Figure S1 in Supplement 1; Table S3 in Supplement 2) (19, 20, 21, 22, 23, 24, 25, 26, 27, 28). Full summary statistics of
Discussion
Psychiatric disorders affect a significant proportion of the population and incur an extremely heavy disease burden worldwide (1, 2, 3). Novel approaches for preventing and treating psychiatric disorders are urgently needed (1,4,5). In this study, we conducted MR studies to systematically screen for circulating proteins that are likely to play a role in the etiology of such disorders, thereby providing a shortlist of potentially modifiable targets for therapeutic development.
We identified 9
Acknowledgments and Disclosures
The JBR research group is supported by the Canadian Institutes of Health Research (CIHR: 365825; Grant No. 409511), the Lady Davis Institute of the Jewish General Hospital, the Canadian Foundation for Innovation, the National Institutes of Health Foundation, Cancer Research UK, Genome Québec, the Public Health Agency of Canada, and the Fonds de Recherche Québec Santé. TwinsUK is funded by the Wellcome Trust, the Medical Research Council, and the European Union; the National Institute for Health
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