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Exploring the genetic overlap between twelve psychiatric disorders

Authors :: Cato Romero
Josefin Werme
Philip R. Jansen
Joel Gelernter
Murray B. Stein
Daniel Levey
Renato Polimanti
Christiaan de Leeuw
Danielle Posthuma
Mats Nagel
Sophie van der Sluis
Human Genetics
ARD - Amsterdam Reproduction and Development
Complex Trait Genetics
Amsterdam Neuroscience - Complex Trait Genetics
Human genetics
Amsterdam Neuroscience - Compulsivity, Impulsivity & Attention
Amsterdam Reproduction & Development (AR&D)
Source :: Romero, C, Werme, J, Jansen, P R, Gelernter, J, Stein, M B, Levey, D, Polimanti, R, de Leeuw, C, Posthuma, D, Nagel, M & van der Sluis, S 2022, ' Exploring the genetic overlap between twelve psychiatric disorders ', Nature Genetics, vol. 54, no. 12, pp. 1795-1802 . https://doi.org/10.1038/s41588-022-01245-2, Nature genetics, 54(12), 1795-1802. Nature Publishing Group, Nature Genetics, 54(12), 1795-1802. Nature Publishing Group, Romero, C, Werme, J, Jansen, P R, Gelernter, J, Stein, M B, Levey, D, Polimanti, R, de Leeuw, C, Posthuma, D, Nagel, M & van der Sluis, S 2022, ' Exploring the genetic overlap between twelve psychiatric disorders ', Nature genetics, vol. 54, no. 12, pp. 1795-1802 . https://doi.org/10.1038/s41588-022-01245-2
Publication Year :: 2022
Publisher :: Springer Science and Business Media LLC, 2022.
Abstract: The widespread comorbidity among psychiatric disorders demonstrated in epidemiological studies1–5 is mirrored by non-zero, positive genetic correlations from large-scale genetic studies6–10. To identify shared biological processes underpinning this observed phenotypic and genetic covariance and enhance molecular characterization of general psychiatric disorder liability11–13, we used several strategies aimed at uncovering pleiotropic, that is, cross-trait-associated, single-nucleotide polymorphisms (SNPs), genes and biological pathways. We conducted cross-trait meta-analysis on 12 psychiatric disorders to identify pleiotropic SNPs. The meta-analytic signal was driven by schizophrenia, hampering interpretation and joint biological characterization of the cross-trait meta-analytic signal. Subsequent pairwise comparisons of psychiatric disorders identified substantial pleiotropic overlap, but mainly among pairs of psychiatric disorders, and mainly at less stringent P-value thresholds. Only annotations related to evolutionarily conserved genomic regions were significant for multiple (9 out of 12) psychiatric disorders. Overall, identification of shared biological mechanisms remains challenging due to variation in power and genetic architecture between psychiatric disorders.