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A decade in psychiatric GWAS research

Abstract

After more than 10 years of accumulated efforts, genome-wide association studies (GWAS) have led to many findings, most of which have been deposited into the GWAS Catalog. Between GWAS’s inception and March 2017, the GWAS Catalog has collected 2429 studies, 1818 phenotypes, and 28,462 associated SNPs. We reclassified the psychology-related phenotypes into 217 reclassified phenotypes, which accounted for 514 studies and 7052 SNPs. In total, 1223 of the SNPs reached genome-wide significance. Of these, 147 were replicated for the same psychological trait in different studies. Another 305 SNPs were replicated within one original study. The SNPs rs2075650 and rs4420638 were linked to the most replications within a single reclassified phenotype or very similar reclassified phenotypes; both were associated with Alzheimer’s disease (AD). Schizophrenia was associated with 74 within-phenotype SNPs reported in independents studies. Alzheimer’s disease and schizophrenia were both linked to some physical phenotypes, including cholesterol and body mass index, through common GWAS signals. Alzheimer’s disease also shared risk SNPs with age-related phenotypes such as age-related macular degeneration and longevity. Smoking-related SNPs were linked to lung cancer and respiratory function. Alcohol-related SNPs were associated with cardiovascular and digestive system phenotypes and disorders. Two separate studies also identified a shared risk SNP for bipolar disorder and educational attainment. This review revealed a list of reproducible SNPs worthy of future functional investigation. Additionally, by identifying SNPs associated with multiple phenotypes, we illustrated the importance of studying the relationships among phenotypes to resolve the nature of their causal links. The insights within this review will hopefully pave the way for future evidence-based genetic studies.

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Acknowledgements

We thank Dr. Elliot S. Gershon for valuable discussions and comments.

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Horwitz, T., Lam, K., Chen, Y. et al. A decade in psychiatric GWAS research. Mol Psychiatry 24, 378–389 (2019). https://doi.org/10.1038/s41380-018-0055-z

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