Conditional GWAS analysis to identify disorder-specific SNPs for psychiatric disorders
| Autor: | Byrne, E., Zhu, Z., Qi, T., Skene, N., Bryois, J., Pardinas, A., Stahl, E., Smoller, J., Rietschel, N., Bipolar Working Group, of the Psychiatric Genomics Consortium, Major Depressive Disorder Working Group of the, Psychiatric Genomics Consortium, Owen, M., Walters, J., O’Donovan, M., McGrath, J., Hjerling-Leffler, J., Sullivan, P., Goddard, M., Visscher, P., Yang, J., Wray, N., Gordon-Smith, Katherine, Jones, Lisa, Perry, Amy |
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| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
medicine.medical_specialty Bipolar Disorder LOCI BF Single-nucleotide polymorphism Genome-wide association study Polymorphism Single Nucleotide Article 03 medical and health sciences Cellular and Molecular Neuroscience 0302 clinical medicine Pleiotropy medicine SNP Humans Genetic Predisposition to Disease Bipolar disorder GENOME-WIDE ASSOCIATION Psychiatry Molecular Biology Depression (differential diagnoses) RISK business.industry BIPOLAR DISORDER RETROMER COMPLEX medicine.disease STATISTICS Psychiatry and Mental health 030104 developmental biology Schizophrenia Attention Deficit Disorder with Hyperactivity RC0321 Autism business 030217 neurology & neurosurgery Genome-Wide Association Study NEUROTROPHIC FACTOR |
| Zdroj: | Byrne, E M, Zhu, Z, Qi, T, Skene, N G, Bryois, J, Pardinas, A F, Stahl, E, Smoller, J W, Rietschel, M, Owen, M J, Walters, J T R, O'Donovan, M C, McGrath, J G, Hjerling-Leffler, J, Sullivan, P F, Goddard, M E, Visscher, P M, Yang, J, Wray, N R & Bipolar Working Group of the Psychiatric Genomics Consortium 2021, ' Conditional GWAS analysis to identify disorder-specific SNPs for psychiatric disorders ', Molecular Psychiatry, vol. 26, no. 6, pp. 2070-2081 . https://doi.org/10.1038/s41380-020-0705-9 Print: 1359-4184 Molecular psychiatry |
| ISSN: | 1476-5578 1359-4184 |
| Popis: | Substantial genetic liability is shared across psychiatric disorders but less is known about risk variants that are specific to a given disorder. We used multi-trait conditional and joint analysis (mtCOJO) to adjust GWAS summary statistics of one disorder for the effects of genetically correlated traits to identify putative disorder-specific SNP associations. We applied mtCOJO to summary statistics for five psychiatric disorders from the Psychiatric Genomics Consortium-schizophrenia (SCZ), bipolar disorder (BIP), major depression (MD), attention-deficit hyperactivity disorder (ADHD) and autism (AUT). Most genome-wide significant variants for these disorders had evidence of pleiotropy (i.e., impact on multiple psychiatric disorders) and hence have reduced mtCOJO conditional effect sizes. However, subsets of genome-wide significant variants had larger conditional effect sizes consistent with disorder-specific effects: 15 of 130 genome-wide significant variants for schizophrenia, 5 of 40 for major depression, 3 of 11 for ADHD and 1 of 2 for autism. We show that decreased expression of VPS29 in the brain may increase risk to SCZ only and increased expression of CSE1L is associated with SCZ and MD, but not with BIP. Likewise, decreased expression of PCDHA7 in the brain is linked to increased risk of MD but decreased risk of SCZ and BIP. |
| Databáze: | OpenAIRE |
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