Somatic, positive and negative domains of the Center for Epidemiological Studies Depression (CES-D) scale: a meta-analysis of genome-wide association studies.

TitleSomatic, positive and negative domains of the Center for Epidemiological Studies Depression (CES-D) scale: a meta-analysis of genome-wide association studies.
Publication TypeJournal Article
Year of Publication2016
AuthorsDemirkan, A, Lahti, J, Direk, N, Viktorin, A, Lunetta, KL, Terracciano, A, Nalls, MA, Tanaka, T, Hek, K, Fornage, M, Wellmann, J, Cornelis, MC, Ollila, HM, Yu, L, Pilling, LC, Isaacs, A, Palotie, A, Zhuang, WV, Zonderman, AB, Faul, JD, Sutin, AR, Meirelles, O, Mulas, A, Hofman, A, Uitterlinden, AG, Rivadeneira, F, Perola, M, Zhao, W, Salomaa, V, Yaffe, K, Luik, AI, Liu, Y, Ding, J, Lichtenstein, P, Landén, M, Widen, E, Weir, DR, Llewellyn, DJ, Murray, A, Kardia, SLR, Eriksson, JG, Koenen, KC, Magnusson, PKE, Ferrucci, L, Mosley, TH, Cucca, F, Oostra, BA, Bennett, DA, Paunio, T, Berger, K, Harris, TB, Pedersen, NL, Murabito, JM, Tiemeier, H, van Duijn, CM, Räikkönen, K
Corporate AuthorsNABEC
JournalPsychol Med
Volume46
Issue8
Pagination1613-23
Date Published2016 06
ISSN Number1469-8978
Keywordsdepression, Depressive Disorder, Major, Genome-Wide Association Study, Humans, Polymorphism, Single Nucleotide, Receptor, Melatonin, MT1, Somatoform Disorders
Abstract

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.

URLhttps://www.ncbi.nlm.nih.gov/pubmed/26997408
DOI10.1017/S0033291715002081
User Guide Notes

http://www.ncbi.nlm.nih.gov/pubmed/26997408?dopt=Abstract

Alternate JournalPsychol Med
Citation Key8534
PubMed ID26997408
PubMed Central IDPMC5812462
Grant ListN01HC55018 / HL / NHLBI NIH HHS / United States
Z99 AG999999 / / Intramural NIH HHS / United States
/ DH_ / Department of Health / United Kingdom
R01 AG017917 / AG / NIA NIH HHS / United States
R01 AG032098 / AG / NIA NIH HHS / United States
P30 AG010161 / AG / NIA NIH HHS / United States
N01HC55016 / HL / NHLBI NIH HHS / United States
N01HC55019 / HL / NHLBI NIH HHS / United States
MR/N008324/1 / / Medical Research Council / United Kingdom
R01 AG015819 / AG / NIA NIH HHS / United States
G0802462 / MRC_ / Medical Research Council / United Kingdom
N01HC55020 / HL / NHLBI NIH HHS / United States
G0901254 / MRC_ / Medical Research Council / United Kingdom
ZIA AG000932 / / Intramural NIH HHS / United States
UL1 RR025005 / RR / NCRR NIH HHS / United States
U01 AG009740 / AG / NIA NIH HHS / United States
N01 AG062101 / AG / NIA NIH HHS / United States
U01 HG004402 / HG / NHGRI NIH HHS / United States
N01HC55022 / HL / NHLBI NIH HHS / United States
N01 AG062106 / AG / NIA NIH HHS / United States
N01HC55015 / HL / NHLBI NIH HHS / United States
R01 HL093029 / HL / NHLBI NIH HHS / United States
HHSN268200782096C / HG / NHGRI NIH HHS / United States
WT089062 / WT_ / Wellcome Trust / United Kingdom
N01 AG062103 / AG / NIA NIH HHS / United States
R01 AG029451 / AG / NIA NIH HHS / United States
R01 HL070825 / HL / NHLBI NIH HHS / United States
N01HC25195 / HL / NHLBI NIH HHS / United States
N02HL64278 / HL / NHLBI NIH HHS / United States
RC2 AG036495 / AG / NIA NIH HHS / United States
/ / Wellcome Trust / United Kingdom
N01HC55021 / HL / NHLBI NIH HHS / United States
R01 HL087641 / HL / NHLBI NIH HHS / United States