TY - JOUR T1 - Somatic, positive and negative domains of the Center for Epidemiological Studies Depression (CES-D) scale: a meta-analysis of genome-wide association studies. JF - Psychol Med Y1 - 2016 A1 - Demirkan, A A1 - J. Lahti A1 - Nese Direk A1 - Viktorin, A. A1 - Kathryn L Lunetta A1 - Antonio Terracciano A1 - Michael A Nalls A1 - Toshiko Tanaka A1 - Karin Hek A1 - Myriam Fornage A1 - Jürgen Wellmann A1 - Marilyn C Cornelis A1 - Ollila, H. M. A1 - Lei Yu A1 - Luke C Pilling A1 - Isaacs, A A1 - Aarno Palotie A1 - Wei Vivian Zhuang A1 - Alan B Zonderman A1 - Jessica Faul A1 - Angelina R Sutin A1 - Osorio Meirelles A1 - Mulas, A A1 - Hofman, A A1 - André G Uitterlinden A1 - Fernando Rivadeneira A1 - Markus Perola A1 - Wei Zhao A1 - Veikko Salomaa A1 - Kristine Yaffe A1 - Luik, A I A1 - Yongmei Liu A1 - Ding, J A1 - Paul Lichtenstein A1 - Landén, M A1 - Elisabeth Widen A1 - David R Weir A1 - David J Llewellyn A1 - Murray, A A1 - Sharon L R Kardia A1 - Johan G Eriksson A1 - Karestan C Koenen A1 - Patrik K E Magnusson A1 - Luigi Ferrucci A1 - Thomas H Mosley A1 - Francesco Cucca A1 - Ben A Oostra A1 - David A Bennett A1 - Paunio, T. A1 - Klaus Berger A1 - Tamara B Harris A1 - Nancy L Pedersen A1 - Joanne M Murabito A1 - Henning Tiemeier A1 - Cornelia M van Duijn A1 - Katri Räikkönen KW - depression KW - Depressive Disorder, Major KW - Genome-Wide Association Study KW - Humans KW - Polymorphism, Single Nucleotide KW - Receptor, Melatonin, MT1 KW - Somatoform Disorders AB -

BACKGROUND: Major depressive disorder (MDD) is moderately heritable, however genome-wide association studies (GWAS) for MDD, as well as for related continuous outcomes, have not shown consistent results. Attempts to elucidate the genetic basis of MDD may be hindered by heterogeneity in diagnosis. The Center for Epidemiological Studies Depression (CES-D) scale provides a widely used tool for measuring depressive symptoms clustered in four different domains which can be combined together into a total score but also can be analysed as separate symptom domains.

METHOD: We performed a meta-analysis of GWAS of the CES-D symptom clusters. We recruited 12 cohorts with the 20- or 10-item CES-D scale (32 528 persons).

RESULTS: One single nucleotide polymorphism (SNP), rs713224, located near the brain-expressed melatonin receptor (MTNR1A) gene, was associated with the somatic complaints domain of depression symptoms, with borderline genome-wide significance (p discovery = 3.82 × 10-8). The SNP was analysed in an additional five cohorts comprising the replication sample (6813 persons). However, the association was not consistent among the replication sample (p discovery+replication = 1.10 × 10-6) with evidence of heterogeneity.

CONCLUSIONS: Despite the effort to harmonize the phenotypes across cohorts and participants, our study is still underpowered to detect consistent association for depression, even by means of symptom classification. On the contrary, the SNP-based heritability and co-heritability estimation results suggest that a very minor part of the variation could be captured by GWAS, explaining the reason of sparse findings.

VL - 46 UR - https://www.ncbi.nlm.nih.gov/pubmed/26997408 IS - 8 U1 - http://www.ncbi.nlm.nih.gov/pubmed/26997408?dopt=Abstract ER -