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

Bigdeli, T. B., Ripke, S., Peterson, R. E., Trzaskowski, M., Bacanu, S.-A., Abdellaoui, A., et al. (2017). Genetic effects influencing risk for major depressive disorder in China and Europe. TRANSLATIONAL PSYCHIATRY, 7: e1074. doi:10.1038/tp.2016.292.

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Bigdeli, T. B.1, Autor
Ripke, S.1, Autor
Peterson, R. E.1, Autor
Trzaskowski, M.1, Autor
Bacanu, S-A1, Autor
Abdellaoui, A.1, Autor
Andlauer, T.F.M.2, Autor           
Beekman, A. T. F.1, Autor
Berger, K.1, Autor
Blackwood, D. H. R.1, Autor
Boomsma, D. I.1, Autor
Breen, G.1, Autor
Buttenschon, H. N.1, Autor
Byrne, E. M.1, Autor
Cichon, S.1, Autor
Clarke, T-K1, Autor
Couvy-Duchesne, B.1, Autor
Craddock, N.1, Autor
de Geus, E. J. C.1, Autor
Degenhardt, F.1, Autor
Dunn, E. C.1, AutorEdwards, A. C.1, AutorFanous, A. H.1, AutorForstner, A. J.1, AutorFrank, J.1, AutorGill, M.1, AutorGordon, S. D.1, AutorGrabe, H. J.1, AutorHamilton, S. P.1, AutorHardiman, O.1, AutorHayward, C.1, AutorHeath, A. C.1, AutorHenders, A. K.1, AutorHerms, S.1, AutorHickie, I. B.1, AutorHoffmann, P.1, AutorHomuth, G.1, AutorHottenga, J-J1, AutorIsing, M3, Autor           Jansen, R.1, AutorKloiber, S.3, Autor           Knowles, J. A.1, AutorLang, M.1, AutorLi, Q. S.1, AutorLucae, S.3, Autor           MacIntyre, D. J.1, AutorMadden, P. A. F.1, AutorMartin, N. G.1, AutorMcGrath, P. J.1, AutorMcGuffin, P.1, AutorMcIntosh, A. M.1, AutorMedland, S. E.1, AutorMehta, D.1, AutorMiddeldorp, C. M.1, AutorMilaneschi, Y.1, AutorMontgomery, G. W.1, AutorMors, O.1, AutorMüller-Myhsok, B.3, Autor           Nauck, M.1, AutorNyholt, D. R.1, AutorNoethen, M. M.1, AutorOwen, M. J.1, AutorPenninx, B. W. J. H.1, AutorPergadia, M. L.1, AutorPerlis, R. H.1, AutorPeyrot, W. J.1, AutorPorteous, D. J.1, AutorPotash, J. B.1, AutorRice, J. P.1, AutorRietschel, M.1, AutorRiley, B. P.1, AutorRivera, M.1, AutorSchoevers, R.1, AutorSchulze, T. G.1, AutorShi, J.1, AutorShyn, S. I.1, AutorSmit, J. H.1, AutorSmoller, J. W.1, AutorStreit, F.1, AutorStrohmaier, J.1, AutorTeumer, A.1, AutorTreutlein, J.1, AutorVan der Auwera, S.1, Autorvan Grootheest, G.1, Autorvan Hemert, A. M.1, AutorVoelzke, H.1, AutorWebb, B. T.1, AutorWeissman, M. M.1, AutorWellmann, J.1, AutorWillemsen, G.1, AutorWitt, S. H.1, AutorLevinson, D. F.1, AutorLewis, C. M.1, AutorWray, N. R.1, AutorFlint, J.1, AutorSullivan, P. F.1, AutorKendler, K. S.1, Autor mehr..
Affiliations:
1External Organizations, ou_persistent22              
2Dept. Translational Research in Psychiatry, Max Planck Institute of Psychiatry, Max Planck Society, ou_2035295              
3Max Planck Institute of Psychiatry, Max Planck Society, ou_1607137              

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 Zusammenfassung: Major depressive disorder (MDD) is a common, complex psychiatric disorder and a leading cause of disability worldwide. Despite twin studies indicating its modest heritability (similar to 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.

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Sprache(n): eng - English
 Datum: 2017-03-28
 Publikationsstatus: Online veröffentlicht
 Seiten: 7
 Ort, Verlag, Ausgabe: -
 Inhaltsverzeichnis: -
 Art der Begutachtung: -
 Identifikatoren: ISI: 000397770800004
DOI: 10.1038/tp.2016.292
 Art des Abschluß: -

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Titel: TRANSLATIONAL PSYCHIATRY
Genre der Quelle: Zeitschrift
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Ort, Verlag, Ausgabe: -
Seiten: - Band / Heft: 7 Artikelnummer: e1074 Start- / Endseite: - Identifikator: ISSN: 2158-3188