Genome-wide association study identifies five new schizophrenia loci.
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Ripke S, Sanders AR, Kendler KS, Levinson DF, Sklar P, Holmans PA, Lin DY, Duan J, Ophoff RA, Andreassen OA, Scolnick E, Cichon S, St Clair D, Corvin A, Gurling H, Werge T, Rujescu D, Blackwood DH, Pato CN, Malhotra AK, Purcell S, Dudbridge F, Neale BM, Rossin L, Visscher PM, Posthuma D, Ruderfer DM, Fanous A, Stefansson H, Steinberg S, Mowry BJ, Golimbet V, De Hert M, Jonsson EG, Bitter I, Pietilainen OP, Collier DA, Tosato S, Agartz I, Albus M, Alexander M, Amdur RL, Amin F, Bass N, Bergen SE, Black DW, B?rglum AD, Brown MA, Bruggeman R, Buccola NG, Byerley WF, Cahn W, Cantor RM, Carr VJ, Catts SV, Choudhury K, Cloninger CR, Cormican P, Craddock N, Danoy PA, Datta S, de Haan L, Demontis D, Dikeos D, Djurovic S, Donnelly P, Donohoe G, Duong L, Dwyer S, Fink-Jensen A, Freedman R, Freimer NB, Friedl M, Georgieva L, Giegling I, Gill M, Glenth?j B, Godard S, Hamshere M, Hansen M, Hansen T, Hartmann AM, Henskens FA, Hougaard DM, Hultman CM, Ingason A, Jablensky AV, Jakobsen KD, Jay M, Jurgens G, Kahn RS, Keller MC, Kenis G, Kenny E, Kim Y, Kirov GK, Konnerth H, Konte B, Krabbendam L, Krasucki R, Lasseter VK, Laurent C, Lawrence J, Lencz T, Lerer FB, Liang KY, Lichtenstein P, Lieberman JA, Linszen DH, Lonnqvist J, Loughland CM, Maclean AW, Maher BS, Maier W, Mallet J, Malloy P, Mattheisen M, Mattingsdal M, McGhee KA, McGrath JJ, McIntosh A, McLean DE, McQuillin A, Melle I, Michie PT, Milanova V, Morris DW, Mors O, Mortensen PB, Moskvina V, Muglia P, Myin-Germeys I, Nertney DA, Nestadt G, Nielsen J, Nikolov I, Nordentoft M, Norton N, Nothen MM, O'Dushlaine CT, Olincy A, Olsen L, O'Neill FA, Orntoft TF, Owen MJ, Pantelis C, Papadimitriou G, Pato MT, Peltonen L, Petursson H, Pickard B, Pimm J, Pulver AE, Puri V, Quested D, Quinn EM, Rasmussen HB, Rethelyi JM, Ribble R, Rietschel M, Riley BP, Ruggeri M, Schall U, Schulze TG, Schwab SG, Scott RJ, Shi J, Sigurdsson E, Silverman JM, Spencer CC, Stefansson K, Strange A, Strengman E, Stroup TS, Suvisaari J, Terenius L, Thirumalai S, Thygesen JH, Timm S, Toncheva D, van den Oord E, van Os J, van Winkel R, Veldink J, Walsh D, Wang AG, Wiersma D, Wildenauer DB, Williams HJ, Williams NM, Wormley B, Zammit S, Sullivan PF, O'Donovan MC, Daly MJ, Gejman PV, Genome-wide association study identifies five new schizophrenia loci., Nature genetics, 43, 10, 2011, 969-976Download Item:
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Abstract:
We examined the role of common genetic variation in schizophrenia in a genome-wide association
study of substantial size: a stage 1 discovery sample of 21,856 individuals of European ancestry
and a stage 2 replication sample of 29,839 independent subjects. The combined stage 1 and 2
analysis yielded genome-wide significant associations with schizophrenia for seven loci, five of
which are new (1p21.3, 2q32.3, 8p23.2, 8q21.3 and 10q24.32-q24.33) and two of which have been
previously implicated (6p21.32-p22.1 and 18q21.2). The strongest new finding (
P
= 1.6 ? 10
?
11
)
was with rs1625579 within an intron of a putative primary transcript for
MIR137
(microRNA
137), a known regulator of neuronal development. Four other schizophrenia loci achieving
genome-wide significance contain predicted targets of
MIR137
, suggesting
MIR137
-mediated
dysregulation as a previously unknown etiologic mechanism in schizophrenia. In a joint analysis
with a bipolar disorder sample (16,374 affected individuals and 14,044 controls), three loci
reached genome-wide significance:
CACNA1C
(rs4765905,
P
= 7.0 ? 10
?
9
),
ANK3
(rs10994359,
P
= 2.5 ? 10
?
8
) and the
ITIH3-ITIH4
region (rs2239547,
P
= 7.8 ? 10
?
9
).
Author's Homepage:
http://people.tcd.ie/acorvinhttp://people.tcd.ie/morrisdw
http://people.tcd.ie/mgill
http://people.tcd.ie/donoghug
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Nature genetics;43;
10;
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