Direk, Nese; Williams, Stephanie; Smith, Jennifer A.; Ripke, Stephan; Air, Tracy; Amare, Azmeraw T.; Amin, Najaf; Baune, Bernhard T.; Bennett, David A.; Blackwood, Douglas H. R.; Boomsma, Dorret; Breen, Gerome; Buttenschon, Henriette N.; Byrne, Enda M.; Borglum, Anders D.; Castelao, Enrique; Cichon, Sven; Clarke, Toni-Kim; Cornelis, Marilyn C.; Dannlowski, Udo; Jager, Philip L. de; Demirkan, Ayse; Domenici, Enrico; Duijn, Cornelia M. van; Dunn, Erin C.; Eriksson, Johan G.; Esko, Tonu; Faul, Jessica D.; Ferrucci, Luigi; Fornage, Myriam; Geus, Eco de; Gill, Michael; Gordon, Scott D.; Grabe, Hans Jörgen; Grootheest, Gerard van; Hamilton, Steven P.; Hartman, Catharina A.; Heath, Andrew C.; Hek, Karin; Hofman, Albert; Homuth, Georg; Horn, Carsten; Hottenga, Jouke Jan; Kardia, Sharon L. R.; Kloiber, Stefan; Koenen, Karestan; Kutalik, Zoltan; Ladwig, Karl-Heinz; Lahti, Jari; Levinson, Douglas F.; Lewis, Cathryn M.; Lewis, Glyn; Li, Qingqin S.; Llewellyn, David J.; Lucae, Susanne; Lunetta, Kathryn L.; MacIntyre, Donald J.; Madden, Pamela; Martin, Nicholas G.; McIntosh, Andrew M.; Metspalu, Andres; Milaneschi, Yuri; Montgomery, Grant W.; Mors, Ole; Mosley, Thomas H.; Murabito, Joanne M.; Müller-Myhsok, Bertram; Nöthen, Markus M.; Nyholt, Dale R.; O'Donovan, Michael C.; Penninx, Brenda W.; Pergadia, Michele L.; Perlis, Roy; Potash, James B.; Preisig, Martin; Purcell, Shaun M.; Quiroz, Jörge A.; Räikkönen, Katri; Rice, John P.; Rietschel, Marcella; Rivera, Margarita; Schulze, Thomas G.; Shi, Jianxin; Shyn, Stanley; Sinnamon, Grant C.; Smit, Johannes H.; Smoller, Jordan W.; Snieder, Harold; Tanaka, Toshiko; Tansey, Katherine E.; Teumer, Alexander; Uher, Rudolf; Umbricht, Daniel; Auwera, Sandra van der; Ware, Erin B.; Weir, David R.; Weissman, Myrna M.; Willemsen, Gonneke; Yang, Jingyun; Zhao, Wei; Tiemeier, Henning; Sullivan, Patrick F. (2017): An Analysis of Two Genome-wide Association Meta-analyses Identifies a New Locus for Broad Depression Phenotype. In: Biological Psychiatry, Vol. 82, No. 5: pp. 322-329 |
Abstract
BACKGROUND: The genetics of depression has been explored in genome-wide association studies that focused on either major depressive disorder or depressive symptoms with mostly negative findings. A broad depression phenotype including both phenotypes has not been tested previously using a genome-wide association approach. We aimed to identify genetic polymorphisms significantly associated with a broad phenotype from depressive symptoms to major depressive disorder. METHODS: We analyzed two prior studies of 70,017 participants of European ancestry from general and clinical populations in the discovery stage. We performed a replication meta-analysis of 28,328 participants. Single nucleotide polymorphism (SNP)-based heritability and genetic correlations were calculated using linkage disequilibrium score regression. Discovery and replication analyses were performed using a p-value-based meta-analysis. Lifetime major depressive disorder and depressive symptom scores were used as the outcome measures. RESULTS: The SNP-based heritability of major depressive disorder was 0.21 (SE = 0.02), the SNP-based heritability of depressive symptoms was 0.04 (SE = 0.01), and their genetic correlation was 1.001 (SE = 0.2). We found one genome-wide significant locus related to the broad depression phenotype (rs9825823, chromosome 3: 61,082,153, p = 8.2 x 10(-9)) located in an intron of the FHIT gene. We replicated this SNP in independent samples (p = .02) and the overall meta-analysis of the discovery and replication cohorts (1.0 x 10(-9)). CONCLUSIONS: This large study identified a new locus for depression. Our results support a continuum between depressive symptoms and major depressive disorder. A phenotypically more inclusive approach may help to achieve the large sample sizes needed to detect susceptibility loci for depression.
Item Type: | Journal article |
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Faculties: | Medicine |
Subjects: | 600 Technology > 610 Medicine and health |
ISSN: | 0006-3223 |
Language: | English |
ID Code: | 51656 |
Deposited On: | 14. Jun 2018 09:47 |
Last Modified: | 04. Nov 2020 13:30 |
- BASE
- Direk, Nese
- Williams, Stephanie
- Smith, Jennifer A.
- Ripke, Stephan
- Air, Tracy
- Amare, Azmeraw T.
- Amin, Najaf
- Baune, Bernhard T.
- Bennett, David A.
- Blackwood, Douglas H. R.
- Boomsma, Dorret
- Breen, Gerome
- Buttenschon, Henriette N.
- Byrne, Enda M.
- Borglum, Anders D.
- Castelao, Enrique
- Cichon, Sven
- Clarke, Toni-Kim
- Cornelis, Marilyn C.
- Dannlowski, Udo
- Jager, Philip L. de
- Demirkan, Ayse
- Domenici, Enrico
- Duijn, Cornelia M. van
- Dunn, Erin C.
- Eriksson, Johan G.
- Esko, Tonu
- Faul, Jessica D.
- Ferrucci, Luigi
- Fornage, Myriam
- Geus, Eco de
- Gill, Michael
- Gordon, Scott D.
- Grabe, Hans Jörgen
- Grootheest, Gerard van
- Hamilton, Steven P.
- Hartman, Catharina A.
- Heath, Andrew C.
- Hek, Karin
- Hofman, Albert
- Homuth, Georg
- Horn, Carsten
- Hottenga, Jouke Jan
- Kardia, Sharon L. R.
- Kloiber, Stefan
- Koenen, Karestan
- Kutalik, Zoltan
- Ladwig, Karl-Heinz
- Lahti, Jari
- Levinson, Douglas F.
- Lewis, Cathryn M.
- Lewis, Glyn
- Li, Qingqin S.
- Llewellyn, David J.
- Lucae, Susanne
- Lunetta, Kathryn L.
- MacIntyre, Donald J.
- Madden, Pamela
- Martin, Nicholas G.
- McIntosh, Andrew M.
- Metspalu, Andres
- Milaneschi, Yuri
- Montgomery, Grant W.
- Mors, Ole
- Mosley, Thomas H.
- Murabito, Joanne M.
- Müller-Myhsok, Bertram
- Nöthen, Markus M.
- Nyholt, Dale R.
- O'Donovan, Michael C.
- Penninx, Brenda W.
- Pergadia, Michele L.
- Perlis, Roy
- Potash, James B.
- Preisig, Martin
- Purcell, Shaun M.
- Quiroz, Jörge A.
- Räikkönen, Katri
- Rice, John P.
- Rietschel, Marcella
- Rivera, Margarita
- Schulze, Thomas G.
- Shi, Jianxin
- Shyn, Stanley
- Sinnamon, Grant C.
- Smit, Johannes H.
- Smoller, Jordan W.
- Snieder, Harold
- Tanaka, Toshiko
- Tansey, Katherine E.
- Teumer, Alexander
- Uher, Rudolf
- Umbricht, Daniel
- Auwera, Sandra van der
- Ware, Erin B.
- Weir, David R.
- Weissman, Myrna M.
- Willemsen, Gonneke
- Yang, Jingyun
- Zhao, Wei
- Tiemeier, Henning
- Sullivan, Patrick F.
- Google Scholar
- Direk, Nese
- Williams, Stephanie
- Smith, Jennifer A.
- Ripke, Stephan
- Air, Tracy
- Amare, Azmeraw T.
- Amin, Najaf
- Baune, Bernhard T.
- Bennett, David A.
- Blackwood, Douglas H. R.
- Boomsma, Dorret
- Breen, Gerome
- Buttenschon, Henriette N.
- Byrne, Enda M.
- Borglum, Anders D.
- Castelao, Enrique
- Cichon, Sven
- Clarke, Toni-Kim
- Cornelis, Marilyn C.
- Dannlowski, Udo
- Jager, Philip L. de
- Demirkan, Ayse
- Domenici, Enrico
- Duijn, Cornelia M. van
- Dunn, Erin C.
- Eriksson, Johan G.
- Esko, Tonu
- Faul, Jessica D.
- Ferrucci, Luigi
- Fornage, Myriam
- Geus, Eco de
- Gill, Michael
- Gordon, Scott D.
- Grabe, Hans Jörgen
- Grootheest, Gerard van
- Hamilton, Steven P.
- Hartman, Catharina A.
- Heath, Andrew C.
- Hek, Karin
- Hofman, Albert
- Homuth, Georg
- Horn, Carsten
- Hottenga, Jouke Jan
- Kardia, Sharon L. R.
- Kloiber, Stefan
- Koenen, Karestan
- Kutalik, Zoltan
- Ladwig, Karl-Heinz
- Lahti, Jari
- Levinson, Douglas F.
- Lewis, Cathryn M.
- Lewis, Glyn
- Li, Qingqin S.
- Llewellyn, David J.
- Lucae, Susanne
- Lunetta, Kathryn L.
- MacIntyre, Donald J.
- Madden, Pamela
- Martin, Nicholas G.
- McIntosh, Andrew M.
- Metspalu, Andres
- Milaneschi, Yuri
- Montgomery, Grant W.
- Mors, Ole
- Mosley, Thomas H.
- Murabito, Joanne M.
- Müller-Myhsok, Bertram
- Nöthen, Markus M.
- Nyholt, Dale R.
- O'Donovan, Michael C.
- Penninx, Brenda W.
- Pergadia, Michele L.
- Perlis, Roy
- Potash, James B.
- Preisig, Martin
- Purcell, Shaun M.
- Quiroz, Jörge A.
- Räikkönen, Katri
- Rice, John P.
- Rietschel, Marcella
- Rivera, Margarita
- Schulze, Thomas G.
- Shi, Jianxin
- Shyn, Stanley
- Sinnamon, Grant C.
- Smit, Johannes H.
- Smoller, Jordan W.
- Snieder, Harold
- Tanaka, Toshiko
- Tansey, Katherine E.
- Teumer, Alexander
- Uher, Rudolf
- Umbricht, Daniel
- Auwera, Sandra van der
- Ware, Erin B.
- Weir, David R.
- Weissman, Myrna M.
- Willemsen, Gonneke
- Yang, Jingyun
- Zhao, Wei
- Tiemeier, Henning
- Sullivan, Patrick F.