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., Andlauer, T. F. M., Beekman, A. T. F., Berger, K., Blackwood, D. H. R., Boomsma, D. I., Breen, G., Buttenschon, H. N., Byrne, E. M., Cichon, S., Clarke, T-K, Couvy-Duchesne, B., Craddock, N., de Geus, E. J. C., Degenhardt, F., Dunn, E. C., Edwards, A. C., Fanous, A. H., Forstner, A. J., Frank, J., Gill, M., Gordon, S. D., Grabe, H. J., Hamilton, S. P., Hardiman, O., Hayward, C., Heath, A. C., Henders, A. K., Herms, S., Hickie, I. B., Hoffmann, P., Homuth, G., Hottenga, J-J, Ising, M., Jansen, R., Kloiber, S., Knowles, J. A., Lang, M., Li, Q. S., Lucae, S., MacIntyre, D. J., Madden, P. A. F., Martin, N. G., McGrath, P. J., McGuffin, P., McIntosh, A. M., Medland, S. E., Mehta, D., Middeldorp, C. M., Milaneschi, Y., Montgomery, G. W., Mors, O., Mueller-Myhsok, B., Nauck, M., Nyholt, D. R., Noethen, M. M., Owen, M. J., Penninx, B. W. J. H., Pergadia, M. L., Perlis, R. H., Peyrot, W. J., Porteous, D. J., Potash, J. B., Rice, J. P., Rietschel, M., Riley, B. P., Rivera, M., Schoevers, R., Schulze, T. G., Shi, J., Shyn, S. I., Smit, J. H., Smoller, J. W., Streit, F., Strohmaier, J., Teumer, A., Treutlein, J., Van der Auwera, S., van Grootheest, G., van Hemert, A. M., Voelzke, H., Webb, B. T., Weissman, M. M., Wellmann, J., Willemsen, G., Witt, S. H., Levinson, D. F., Lewis, C. M., Wray, N. R., Flint, J., Sullivan, P. F. and Kendler, K. S. (2017) Genetic effects influencing risk for major depressive disorder in China and Europe. Translational Psychiatry, 7 3: e1074-e1074. doi:10.1038/tp.2016.292


Author Bigdeli, T. B.
Ripke, S.
Peterson, R. E.
Trzaskowski, M.
Bacanu, S-A
Abdellaoui, A.
Andlauer, T. F. M.
Beekman, A. T. F.
Berger, K.
Blackwood, D. H. R.
Boomsma, D. I.
Breen, G.
Buttenschon, H. N.
Byrne, E. M.
Cichon, S.
Clarke, T-K
Couvy-Duchesne, B.
Craddock, N.
de Geus, E. J. C.
Degenhardt, F.
Dunn, E. C.
Edwards, A. C.
Fanous, A. H.
Forstner, A. J.
Frank, J.
Gill, M.
Gordon, S. D.
Grabe, H. J.
Hamilton, S. P.
Hardiman, O.
Hayward, C.
Heath, A. C.
Henders, A. K.
Herms, S.
Hickie, I. B.
Hoffmann, P.
Homuth, G.
Hottenga, J-J
Ising, M.
Jansen, R.
Kloiber, S.
Knowles, J. A.
Lang, M.
Li, Q. S.
Lucae, S.
MacIntyre, D. J.
Madden, P. A. F.
Martin, N. G.
McGrath, P. J.
McGuffin, P.
McIntosh, A. M.
Medland, S. E.
Mehta, D.
Middeldorp, C. M.
Milaneschi, Y.
Montgomery, G. W.
Mors, O.
Mueller-Myhsok, B.
Nauck, M.
Nyholt, D. R.
Noethen, M. M.
Owen, M. J.
Penninx, B. W. J. H.
Pergadia, M. L.
Perlis, R. H.
Peyrot, W. J.
Porteous, D. J.
Potash, J. B.
Rice, J. P.
Rietschel, M.
Riley, B. P.
Rivera, M.
Schoevers, R.
Schulze, T. G.
Shi, J.
Shyn, S. I.
Smit, J. H.
Smoller, J. W.
Streit, F.
Strohmaier, J.
Teumer, A.
Treutlein, J.
Van der Auwera, S.
van Grootheest, G.
van Hemert, A. M.
Voelzke, H.
Webb, B. T.
Weissman, M. M.
Wellmann, J.
Willemsen, G.
Witt, S. H.
Levinson, D. F.
Lewis, C. M.
Wray, N. R.
Flint, J.
Sullivan, P. F.
Kendler, K. S.
Title Genetic effects influencing risk for major depressive disorder in China and Europe
Journal name Translational Psychiatry   Check publisher's open access policy
ISSN 2158-3188
Publication date 2017-03-28
Year available 2017
Sub-type Article (original research)
DOI 10.1038/tp.2016.292
Open Access Status DOI
Volume 7
Issue 3
Start page e1074
End page e1074
Total pages 7
Place of publication London, United Kingdom
Publisher Nature Publishing Group
Language eng
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.
Formatted 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.
Keyword Psychiatry
Psychiatry
Q-Index Code C1
Q-Index Status Provisional Code
Grant ID WT090532/Z/09/Z
MH100549
NWO 480-05-003
104036/Z/14/Z
CZD/16/6
HR03006
01GS08144
BMBF01ZX1314G
NIMH R01
U54 RR020278
G0701420
G0000647
LSHB-CT-2003-503428
01ES0811
FKZ 01GS0481
904-61-193
2008.024
HEALTH-F4-2007-201413
230374
MH081802
241944
FT0991360
QLG2-CT-2002-01254
AA07535
01ZZ9603
GR1912/5-1
U54LM008748
R01MH086026
EU/QLRT-2001-01254
Institutional Status UQ

 
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