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A genome-wide association study of depressive symptoms.

TitleA genome-wide association study of depressive symptoms.
Publication TypeJournal Article
Year of Publication2013
AuthorsHek K, Demirkan A, Lahti J, Terracciano A, Teumer A, Cornelis MC, Amin N, Bakshis E, Baumert J, Ding J, Liu Y, Marciante K, Meirelles O, Nalls MA, Sun YV, Vogelzangs N, Yu L, Bandinelli S, Benjamin EJ, Bennett DA, Boomsma D, Cannas A, Coker LH, de Geus E, De Jager PL, Diez-Roux AV, Purcell S, Hu FB, Rimma EB, Hunter DJ, Jensen MK, Curhan G, Rice K, Penman AD, Rotter JI, Sotoodehnia N, Emeny R, Eriksson JG, Evans DA, Ferrucci L, Fornage M, Gudnason V, Hofman A, Illig T, Kardia S, Kelly-Hayes M, Koenen K, Kraft P, Kuningas M, Massaro JM, Melzer D, Mulas A, Mulder CL, Murray A, Oostra BA, Palotie A, Penninx B, Petersmann A, Pilling LC, Psaty B, Rawal R, Reiman EM, Schulz A, Shulman JM, Singleton AB, Smith AV, Sutin AR, Uitterlinden AG, Völzke H, Widen E, Yaffe K, Zonderman AB, Cucca F, Harris T, Ladwig K-H, Llewellyn DJ, Räikkönen K, Tanaka T, van Duijn CM, Grabe HJ, Launer LJ, Lunetta KL, Mosley TH, Newman AB, Tiemeier H
Secondary AuthorsMurabito J
JournalBiol Psychiatry
Volume73
Issue7
Pagination667-78
Date Published2013 Apr 01
ISSN1873-2402
KeywordsAged, Aged, 80 and over, Chromosomes, Human, Pair 5, Depression, Female, Genetic Predisposition to Disease, Genome-Wide Association Study, Humans, Male, Middle Aged, Polymorphism, Single Nucleotide
Abstract

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

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.

DOI10.1016/j.biopsych.2012.09.033
Alternate JournalBiol Psychiatry
PubMed ID23290196
PubMed Central IDPMC3845085
Grant List5UO1CA098233 / CA / NCI NIH HHS / United States
N01HC55020 / HL / NHLBI NIH HHS / United States
AG]916413 / AG / NIA NIH HHS / United States
R01 CA050385 / CA / NCI NIH HHS / United States
UL1RR025005 / RR / NCRR NIH HHS / United States
U01-HG004402 / HG / NHGRI NIH HHS / United States
N02-HL-6-4278 / HL / NHLBI NIH HHS / United States
UL1 RR033176 / RR / NCRR NIH HHS / United States
UL1RR033176 / RR / NCRR NIH HHS / United States
R01 HL075366 / HL / NHLBI NIH HHS / United States
N01AG12100 / AG / NIA NIH HHS / United States
R01 HL101161 / HL / NHLBI NIH HHS / United States
N01HC55018 / HL / NHLBI NIH HHS / United States
UL1 RR025005 / RR / NCRR NIH HHS / United States
K08 AG034290 / AG / NIA NIH HHS / United States
R01 AG015928 / AG / NIA NIH HHS / United States
N01 AG062101 / AG / NIA NIH HHS / United States
P01 CA087969 / CA / NCI NIH HHS / United States
U01 HL080295 / HL / NHLBI NIH HHS / United States
R01 CA067262 / CA / NCI NIH HHS / United States
R01-AG29451 / AG / NIA NIH HHS / United States
N01-AG-1-2109 / AG / NIA NIH HHS / United States
N01-HC-55022 / HC / NHLBI NIH HHS / United States
ZIA AG000183-22 / / Intramural NIH HHS / United States
HL105756 / HL / NHLBI NIH HHS / United States
R01 MD009164 / MD / NIMHD NIH HHS / United States
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N01 HC015103 / HC / NHLBI NIH HHS / United States
N01-HC-55016 / HC / NHLBI NIH HHS / United States
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263 MD 821336 / MD / NIMHD NIH HHS / United States
UL1-RR-024156 / RR / NCRR NIH HHS / United States
R56 AG020098 / AG / NIA NIH HHS / United States
CA87969 / CA / NCI NIH HHS / United States
UL1 RR024156 / RR / NCRR NIH HHS / United States
N01-HC-95159 / HC / NHLBI NIH HHS / United States
263 MD 9164 13 / MD / NIMHD NIH HHS / United States
R01 AG017917 / AG / NIA NIH HHS / United States
1R01AG032098-01A1 / AG / NIA NIH HHS / United States
R01 MH086498 / MH / NIMH NIH HHS / United States
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AG-20098 / AG / NIA NIH HHS / United States
N01HC55022 / HL / NHLBI NIH HHS / United States
CA49449 / CA / NCI NIH HHS / United States
HL087652 / HL / NHLBI NIH HHS / United States
UL1 TR000124 / TR / NCATS NIH HHS / United States
N01 AG062106 / AG / NIA NIH HHS / United States
HHSN268200625226C / / PHS HHS / United States
U01 HG004402 / HG / NHGRI NIH HHS / United States
N01HC55222 / HL / NHLBI NIH HHS / United States
N01-HC-55021 / HC / NHLBI NIH HHS / United States
U01 CA067262 / CA / NCI NIH HHS / United States
R01 CA065725 / CA / NCI NIH HHS / United States
N01-HC-85086 / HC / NHLBI NIH HHS / United States
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CA67262 / CA / NCI NIH HHS / United States
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HHSN268200782096C / HG / NHGRI NIH HHS / United States
HL075366 / HL / NHLBI NIH HHS / United States
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ZIA AG000183-23 / / Intramural NIH HHS / United States
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R01 AG029451 / AG / NIA NIH HHS / United States
N01]AG]821336 / AG / NIA NIH HHS / United States
N01-HC-95169 / HC / NHLBI NIH HHS / United States
N01HC95159 / HL / NHLBI NIH HHS / United States
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N01-HC-75150 / HC / NHLBI NIH HHS / United States
N01-HC-55020 / HC / NHLBI NIH HHS / United States
ZIA AG000196-03 / / Intramural NIH HHS / United States
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DK063491 / DK / NIDDK NIH HHS / United States
P30AG10161 / AG / NIA NIH HHS / United States
N01-HC-85079 / HC / NHLBI NIH HHS / United States
/ / Wellcome Trust / United Kingdom
ZIA AG000197-04 / / Intramural NIH HHS / United States
HL080295 / HL / NHLBI NIH HHS / United States
CA50385 / CA / NCI NIH HHS / United States
P30 AG019610 / AG / NIA NIH HHS / United States
R01 CA049449 / CA / NCI NIH HHS / United States
N01-HC-85239 / HC / NHLBI NIH HHS / United States
N01HC85079 / HL / NHLBI NIH HHS / United States
N01-HC-55018 / HC / NHLBI NIH HHS / United States
N01HC55021 / HL / NHLBI NIH HHS / United States
R01 AG023629 / AG / NIA NIH HHS / United States
R01 HL087641 / HL / NHLBI NIH HHS / United States
AG-023629 / AG / NIA NIH HHS / United States
U01 CA049449 / CA / NCI NIH HHS / United States
K08AG34290 / AG / NIA NIH HHS / United States
R01 AG027058 / AG / NIA NIH HHS / United States
N01 HC045133 / HC / NHLBI NIH HHS / United States
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WT098051 / WT_ / Wellcome Trust / United Kingdom
CA65725 / CA / NCI NIH HHS / United States
ZIA AG000196-04 / / Intramural NIH HHS / United States
N01-HC-65226 / HC / NHLBI NIH HHS / United States