Genetic effects influencing risk for major depressive disorder in China and Europe

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Bigdeli, TB, Ripke, S, Peterson, RE, Trzaskowski, M, Bacanu, S-A, Abdellaoui, A, Andlauer, TFM, Beekman, ATF, Berger, K, Blackwood, DHR et al (show 87 more authors) , Boomsma, DI, Breen, G, Buttenschon, HN, Byrne, EM, Cichon, S, Clarke, T-K, Couvy-Duchesne, B, Craddock, N, de Geus, EJC, Degenhardt, F, Dunn, EC, Edwards, AC, Fanous, AH, Forstner, AJ, Frank, J, Gill, M, Gordon, SD, Grabe, HJ, Hamilton, SP, Hardiman, O, Hayward, C, Heath, AC, Henders, AK, Herms, S, Hickie, IB, Hoffmann, P, Homuth, G, Hottenga, J-J, Ising, M, Jansen, R, Kloiber, S, Knowles, JA, Lang, M, Li, QS, Lucae, S, MacIntyre, DJ, Madden, PAF, Martin, NG, McGrath, PJ, McGuffin, P, McIntosh, AM, Medland, SE, Mehta, D, Middeldorp, CM, Milaneschi, Y, Montgomery, GW, Mors, O, Mueller-Myhsok, B ORCID: 0000-0002-0719-101X, Nauck, M, Nyholt, DR, Noethen, MM, Owen, MJ, Penninx, BWJH, Pergadia, ML, Perlis, RH, Peyrot, WJ, Porteous, DJ, Potash, JB, Rice, JP, Rietschel, M, Riley, BP, Rivera, M, Schoevers, R, Schulze, TG, Shi, J, Shyn, SI, Smit, JH, Smoller, JW, Streit, F, Strohmaier, J, Teumer, A, Treutlein, J, Van der Auwera, S, van Grootheest, G, van Hemert, AM, Voelzke, H, Webb, BT, Weissman, MM, Wellmann, J, Willemsen, G, Witt, SH, Levinson, DF, Lewis, CM, Wray, NR, Flint, J, Sullivan, PF and Kendler, KS (2017) Genetic effects influencing risk for major depressive disorder in China and Europe. TRANSLATIONAL PSYCHIATRY, 7 (3). e1074-.

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Abstract

Major depressive disorder (MDD) is a common, complex psychiatric disorder and a leading cause of disability worldwide. Despite twin studies indicating its modest heritability (~30-40%), extensive heterogeneity and a complex genetic architecture have complicated efforts to detect associated genetic risk variants. We combined single-nucleotide polymorphism (SNP) summary statistics from the CONVERGE and PGC studies of MDD, representing 10 502 Chinese (5282 cases and 5220 controls) and 18 663 European (9447 cases and 9215 controls) subjects. We determined the fraction of SNPs displaying consistent directions of effect, assessed the significance of polygenic risk scores and estimated the genetic correlation of MDD across ancestries. Subsequent trans-ancestry meta-analyses combined SNP-level evidence of association. Sign tests and polygenic score profiling weakly support an overlap of SNP effects between East Asian and European populations. We estimated the trans-ancestry genetic correlation of lifetime MDD as 0.33; female-only and recurrent MDD yielded estimates of 0.40 and 0.41, respectively. Common variants downstream of GPHN achieved genome-wide significance by Bayesian trans-ancestry meta-analysis (rs9323497; log₁₀ Bayes Factor=8.08) but failed to replicate in an independent European sample (P=0.911). Gene-set enrichment analyses indicate enrichment of genes involved in neuronal development and axonal trafficking. We successfully demonstrate a partially shared polygenic basis of MDD in East Asian and European populations. Taken together, these findings support a complex etiology for MDD and possible population differences in predisposing genetic factors, with important implications for future genetic studies.

Item Type:	Article
Uncontrolled Keywords:	Humans, Genetic Predisposition to Disease, Bayes Theorem, Case-Control Studies, Depressive Disorder, Major, Multifactorial Inheritance, Polymorphism, Single Nucleotide, China, Europe, Female, Male, Asian People, White People
Depositing User:	Symplectic Admin
Date Deposited:	02 May 2017 06:20
Last Modified:	13 Feb 2023 23:10
DOI:	10.1038/tp.2016.292
Related URLs:	Author Publisher
URI:	https://livrepository.liverpool.ac.uk/id/eprint/3007193