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Genetic effects influencing risk for major depressive disorder in China and Europe
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 r...
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5404611/ https://www.ncbi.nlm.nih.gov/pubmed/28350396 http://dx.doi.org/10.1038/tp.2016.292 |
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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 Buttenschøn, 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 Müller-Myhsok, B Nauck, M Nyholt, D R Nöthen, 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 Völzke, 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 |
author_facet | 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 Buttenschøn, 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 Müller-Myhsok, B Nauck, M Nyholt, D R Nöthen, 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 Völzke, 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 |
author_sort | Bigdeli, T B |
collection | PubMed |
description | 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; log(10) 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. |
format | Online Article Text |
id | pubmed-5404611 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Nature Publishing Group |
record_format | MEDLINE/PubMed |
spelling | pubmed-54046112017-05-12 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 Buttenschøn, 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 Müller-Myhsok, B Nauck, M Nyholt, D R Nöthen, 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 Völzke, 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 Transl Psychiatry Original Article 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; log(10) 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. Nature Publishing Group 2017-03 2017-03-28 /pmc/articles/PMC5404611/ /pubmed/28350396 http://dx.doi.org/10.1038/tp.2016.292 Text en Copyright © 2017 The Author(s) http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article's Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ |
spellingShingle | Original Article 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 Buttenschøn, 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 Müller-Myhsok, B Nauck, M Nyholt, D R Nöthen, 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 Völzke, 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 Genetic effects influencing risk for major depressive disorder in China and Europe |
title | Genetic effects influencing risk for major depressive disorder in China and Europe |
title_full | Genetic effects influencing risk for major depressive disorder in China and Europe |
title_fullStr | Genetic effects influencing risk for major depressive disorder in China and Europe |
title_full_unstemmed | Genetic effects influencing risk for major depressive disorder in China and Europe |
title_short | Genetic effects influencing risk for major depressive disorder in China and Europe |
title_sort | genetic effects influencing risk for major depressive disorder in china and europe |
topic | Original Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5404611/ https://www.ncbi.nlm.nih.gov/pubmed/28350396 http://dx.doi.org/10.1038/tp.2016.292 |
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