A genome-wide association study of depressive symptoms

Karin Hek, Ayse Demirkan, Jari Lahti, Antonio Terracciano, Alexander Teumer, Marilyn C. Cornelis, Najaf Amin, Erin Bakshis, Jens Baumert, Jingzhong Ding, Yongmei Liu, Kristin Marciante, Osorio Meirelles, Michael A. Nalls, Yan V. Sun, Nicole Vogelzangs, Lei Yu, Stefania Bandinelli, Emelia J. Benjamin, David A. BennettDorret Boomsma, Alessandra Cannas, Laura H. Coker, Eco De Geus, Philip L. De Jager, Ana V. Diez-Roux, Shaun Purcell, Frank B. Hu, Eric B. Rimm, David J. Hunter, Majken K. Jensen, Gary Curhan, Kenneth Rice, Alan D. Penman, Jerome I. Rotter, Nona Sotoodehnia, Rebecca Emeny, Johan G. Eriksson, Denis A. Evans, Luigi Ferrucci, Myriam Fornage, Vilmundur Gudnason, Albert Hofman, Thomas Illig, Sharon Kardia, Margaret Kelly-Hayes, Karestan Koenen, Peter Kraft, Maris Kuningas, Joseph M. Massaro, David Melzer, Antonella Mulas, Cornelis L. Mulder, Anna Murray, Ben A. Oostra, Aarno Palotie, Brenda Penninx, Astrid Petersmann, Luke C. Pilling, Bruce Psaty, Rajesh Rawal, Eric M. Reiman, Andrea Schulz, Joshua M. Shulman, Andrew B. Singleton, Albert V. Smith, Angelina R. Sutin, André G. Uitterlinden, Henry Völzke, Elisabeth Widen, Kristine Yaffe, Alan B. Zonderman, Francesco Cucca, Tamara Harris, Karl Heinz Ladwig, David J. Llewellyn, Katri Räikkönen, Toshiko Tanaka, Cornelia M. Van Duijn, Hans J. Grabe, Lenore J. Launer, Kathryn L. Lunetta, Thomas H. Mosley, Anne B. Newman, Henning Tiemeier*, Joanne Murabito

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

121 Scopus citations


Background: Depression is a heritable trait that exists on a continuum of varying severity and duration. Yet, the search for genetic variants associated with depression has had few successes. We exploit the entire continuum of depression to find common variants for depressive symptoms. Methods: In this genome-wide association study, we combined the results of 17 population-based studies assessing depressive symptoms with the Center for Epidemiological Studies Depression Scale. Replication of the independent top hits (p<1×10-5) was performed in five studies assessing depressive symptoms with other instruments. In addition, we performed a combined meta-analysis of all 22 discovery and replication studies. Results: The discovery sample comprised 34,549 individuals (mean age of 66.5) and no loci reached genome-wide significance (lowest p = 1.05×10-7). Seven independent single nucleotide polymorphisms were considered for replication. In the replication set (n = 16,709), we found suggestive association of one single nucleotide polymorphism with depressive symptoms (rs161645, 5q21, p = 9.19×10-3). This 5q21 region reached genome-wide significance (p = 4.78×10-8) in the overall meta-analysis combining discovery and replication studies (n = 51,258). Conclusions: The results suggest that only a large sample comprising more than 50,000 subjects may be sufficiently powered to detect genes for depressive symptoms.

Original languageEnglish (US)
Pages (from-to)667-678
Number of pages12
JournalBiological psychiatry
Issue number7
StatePublished - Apr 1 2013


  • CHARGE consortium
  • Center for Epidemiologic Studies Depression Scale
  • depression
  • depressive symptoms
  • genetics
  • genome-wide association study
  • meta-analysis

ASJC Scopus subject areas

  • Biological Psychiatry

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