Gene variants associated with schizophrenia in a Norwegian genome-wide study are replicated in a large European cohort.
Gene variants associated with schizophrenia in a Norwegian genome-wide study are replicated in a large European cohort.
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DOI：
10.1016/j.jpsychires.2010.02.002
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发表时间：
2010-09
影响因子：
4.8
通讯作者：
Andreassen OA
中科院分区：
文献类型：
--
作者：
Athanasiu L;Mattingsdal M;Kähler AK;Brown A;Gustafsson O;Agartz I;Giegling I;Muglia P;Cichon S;Rietschel M;Pietiläinen OP;Peltonen L;Bramon E;Collier D;Clair DS;Sigurdsson E;Petursson H;Rujescu D;Melle I;Steen VM;Djurovic S;Andreassen OA
我们在挪威发现的201例病例和305例对照样本（TOP研究）中进行了精神分裂症的全基因组关联研究（GWAS），并在更大的欧洲样本（2663例病例和13，780例对照受试者）中进行了重点复制分析（SGENE-plus研究）。首先，使用AffysseTM全基因组人类SNP阵列6.0对发现样本进行基因分型，并测试了572，888个标记与精神分裂症的关联。发现样本中没有SNP达到全基因组显著性（P < 8.7 × 10−8）。其次，基于GWAS数据，我们在发现TOP样本中选择了1000个具有最低P值的标记，并在复制样本中测试了这些（或基于HapMap的替代物）的关联。在重复样本中，16个位点与精神分裂症相关（名义P值< 0.05，同时OR）。下一步，我们对这两项研究的结果进行了综合分析，并为9 p21上的标记rs7045881，16 p12上的rs 433598和10 q21上的rs 10761482提供了与精神分裂症相关的最强有力证据。这些标记分别位于PLAA、ACSM 1和ANK 3。PLAA以前没有被描述为易感基因，但9 p21暗示为精神分裂症连锁区。ACSM 1已被确定为精神分裂症GWAS研究中的易感基因。ANK 3与精神分裂症的关联是有趣的，鉴于最近ANK 3与双相情感障碍的关联，从而支持这些精神病理实体之间遗传易感性重叠的假设。
We have performed a genome-wide association study (GWAS) of schizophrenia in a Norwegian discovery sample of 201 cases and 305 controls (TOP study) with a focused replication analysis in a larger European sample of 2663 cases and 13,780 control subjects (SGENE-plus study). Firstly, the discovery sample was genotyped with Affymetrix Genome-Wide Human SNP Array 6.0 and 572,888 markers were tested for schizophrenia association. No SNPs in the discovery sample attained genome-wide significance (P < 8.7 × 10−8). Secondly, based on the GWAS data, we selected 1000 markers with the lowest P values in the discovery TOP sample, and tested these (or HapMap-based surrogates) for association in the replication sample. Sixteen loci were associated with schizophrenia (nominal P value < 0.05 and concurring OR) in the replication sample. As a next step, we performed a combined analysis of the findings from these two studies, and the strongest evidence for association with schizophrenia was provided for markers rs7045881 on 9p21, rs433598 on 16p12 and rs10761482 on 10q21. The markers are located in PLAA, ACSM1 and ANK3, respectively. PLAA has not previously been described as a susceptibility gene, but 9p21 is implied as a schizophrenia linkage region. ACSM1 has been identified as a susceptibility gene in a previous schizophrenia GWAS study. The association of ANK3 with schizophrenia is intriguing in light of recent associations of ANK3 with bipolar disorder, thereby supporting the hypothesis of an overlap in genetic susceptibility between these psychopathological entities.
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影响因子：
64.8
作者：
Stefansson, Hreinn;Ophoff, Roel A.;Steinberg, Stacy;Andreassen, Ole A.;Cichon, Sven;Rujescu, Dan;Werge, Thomas;Pietilainen, Olli P. H.;Mors, Ole;Mortensen, Preben B.;Sigurdsson, Engilbert;Gustafsson, Omar;Nyegaard, Mette;Tuulio-Henriksson, Annamari;Ingason, Andres;Hansen, Thomas;Suvisaari, Jaana;Lonnqvist, Jouko;Paunio, Tiina;Borglum, Anders D.;Hartmann, Annette;Fink-Jensen, Anders;Nordentoft, Merete;Hougaard, David;Norgaard-Pedersen, Bent;Bottcher, Yvonne;Olesen, Jes;Breuer, Rene;Moeller, Hans-Jurgen;Giegling, Ina;Rasmussen, Henrik B.;Timm, Sally;Mattheisen, Manuel;Bitter, Istvan;Rethelyi, Janos M.;Magnusdottir, Brynja B.;Sigmundsson, Thordur;Olason, Pall;Mason, Gisli;Gulcher, Jeffrey R.;Haraldsson, Magnus;Fossdal, Ragnheidur;Thorgeirsson, Thorgeir E.;Thorsteinsdottir, Unnur;Ruggeri, Mirella;Tosato, Sarah;Franke, Barbara;Strengman, Eric;Kiemeney, Lambertus A.;Melle, Ingrid;Djurovic, Srdjan;Abramova, Lilia;Kaleda, Vasily;Sanjuan, Julio;de Frutos, Rosa;Bramon, Elvira;Vassos, Evangelos;Fraser, Gillian;Ettinger, Ulrich;Picchioni, Marco;Walker, Nicholas;Toulopoulou, Timi;Need, Anna C.;Ge, Dongliang;Yoon, Joeng Lim;Shianna, Kevin V.;Freimer, Nelson B.;Cantor, Rita M.;Murray, Robin;Kong, Augustine;Golimbet, Vera;Carracedo, Angel;Arango, Celso;Costas, Javier;Joensson, Erik G.;Terenius, Lars;Agartz, Ingrid;Petursson, Hannes;Nothen, Markus M.;Rietschel, Marcella;Matthews, Paul M.;Muglia, Pierandrea;Peltonen, Leena;St Clair, David;Goldstein, David B.;Stefansson, Kari;Collier, David A.
通讯作者：
Collier, David A.
影响因子：
5.3
作者：
Birkenaes, Astrid B.;Opjordsmoen, Stein;Andreassen, Ole A.
通讯作者：
Andreassen, Ole A.
影响因子：
30.8
作者：
Ferreira, Manuel A. R.;O'Donovan, Michael C.;Meng, Yan A.;Jones, Ian R.;Ruderfer, Douglas M.;Jones, Lisa;Fan, Jinbo;Kirov, George;Perlis, Roy H.;Green, Elaine K.;Smoller, Jordan W.;Grozeva, Detelina;Stone, Jennifer;Nikolov, Ivan;Chambert, Kimberly;Hamshere, Marian L.;Nimgaonkar, Vishwajit L.;Moskvina, Valentina;Thase, Michael E.;Caesar, Sian;Sachs, Gary S.;Franklin, Jennifer;Gordon-Smith, Katherine;Ardlie, Kristin G.;Gabriel, Stacey B.;Fraser, Christine;Blumenstiel, Brendan;Defelice, Matthew;Breen, Gerome;Gill, Michael;Morris, Derek W.;Elkin, Amanda;Muir, Walter J.;McGhee, Kevin A.;Williamson, Richard;MacIntyre, Donald J.;MacLean, Alan W.;Clair, David St;Robinson, Michelle;Van Beck, Margaret;Pereira, Ana C. P.;Kandaswamy, Radhika;McQuillin, Andrew;Collier, David A.;Bass, Nicholas J.;Young, Allan H.;Lawrence, Jacob;Ferrier, I. Nicol;Anjorin, Adebayo;Farmer, Anne;Curtis, David;Scolnick, Edward M.;McGuffin, Peter;Daly, Mark J.;Corvin, Aiden P.;Holmans, Peter A.;Blackwood, Douglas H.;Gurling, Hugh M.;Owen, Michael J.;Purcell, Shaun M.;Sklar, Pamela;Craddock, Nick
通讯作者：
Craddock, Nick
影响因子：
11
作者：
通讯作者：
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影响因子：
11
作者：
Baum, A. E.;Akula, N.;McMahon, F. J.
通讯作者：
McMahon, F. J.