Genome-wide association study identifies five new schizophrenia loci

@article{Ripke2011GenomewideAS,
  title={Genome-wide association study identifies five new schizophrenia loci},
  author={Stephan Ripke and Alan R. Sanders and Kenneth S. Kendler and Douglas F. Levinson and Pamela Sklar and Peter A Holmans and Danyu Lin and Jubao Duan and Roel A. Ophoff and Ole Andreas Andreassen and Edward M. Scolnick and Sven Cichon and David M. St. Clair and Aiden P. Corvin and Hugh M D Gurling and Thomas M. Werge and Dan Rujescu and Douglas H.R. Blackwood and Carlos N. Pato and Anil K. Malhotra and Shaun M Purcell and Frank Dudbridge and Benjamin M. Neale and Lizzy Rossin and Peter M. Visscher and Danielle Posthuma and Douglas M. Ruderfer and Ayman H. Fanous and Hreinn Stef{\'a}nsson and Stacy Steinberg and Bryan J. Mowry and Vera Golimbet and Marc De Hert and Erik G. J{\"o}nsson and Istv{\'a}n Bitter and Olli Pietil{\"a}inen and David A. Collier and Sarah Tosato and Ingrid Agartz and M. Albus and Madeline Alexander and Richard L. Amdur and Farooq Amin and Nicholas J Bass and Sarah L Bergen and Donald W. Black and Anders Dupont B{\o}rglum and Matthew A. Brown and Richard Bruggeman and Nancy G. Buccola and William Byerley and Wiepke Cahn and Rita M. Cantor and Vaughan J. Carr and S. V. Catts and Khalid Choudhury and Claude Robert Cloninger and Paul Cormican and Nick Craddock and Patrick A. Danoy and Susmita Datta and Lieuwe Haan and Ditte Demontis and Dimitris Dikeos and Srdjan Djurovic and Peter Donnelly and Gary Donohoe and Linh Tuan Duong and Sarah Dwyer and Anders Fink-Jensen and Robert Freedman and Nelson B. Freimer and Markus Friedl and Lyudmila Georgieva and Ina Giegling and Michael Gill and Birte Yding Glenth{\o}j and Stephanie Godard and Marian L. Hamshere and Mark S. T. Hansen and Thomas Hansen and Annette M. Hartmann and Frans A. Henskens and David Michael Hougaard and Christina M. Hultman and Andr{\'e}s Ingason and Assen Jablensky and Klaus Damgaard Jakobsen and Maurice Jay and Gesche Juergens and Ren{\'e} S. Kahn and Matthew C. Keller and Gunter Kenis and Elaine Kenny and Yunjung Kim and George Kirov and Heike Konnerth and Bettina Konte and Lydia Krabbendam and Robert Krasucki and Virginia K. Lasseter and Claudine Laurent and Jacob Lawrence and Todd Lencz and F. Bernard Lerer and Kung-yee Liang and Paul Lichtenstein and Jeffrey A. Lieberman and Don H. Linszen and Jouko L{\"o}nnqvist and C. M. Loughland and Alan W Maclean and Brion Maher and Wolfgang Maier and Jacques Mallet and Pat Malloy and Manuel Mattheisen and Morten Mattingsdal and Kevin A. McGhee and J J Mcgrath and Andrew M. McIntosh and Duncan E. McLean and Andrew McQuillin and Ingrid Melle and Patricia T. Michie and Vihra Milanova and Derek W. Morris and Ole Mors and Preben Bo Mortensen and Valentina Moskvina and Pierandrea Muglia and Inez Myin-Germeys and Deborah A. Nertney and Gerald Nestadt and Jimmi Nielsen and Ivan Nikolov and Merete Nordentoft and Nadine Norton and Markus M. Noethen and Colm O'Dushlaine and Ann Olincy and Line Olsen and Francis A. O’Neill and Torben F. {\O}rntoft and Michael J. Owen and Christos Pantelis and George N. Papadimitriou and Michele T. Pato and Leena Peltonen and Hannes P{\'e}tursson and Ben S. Pickard and Jonathan Pimm and Ann E. Pulver and Vinay Puri and Digby J. Quested and Emma M. Quinn and Henrik Berg Rasmussen and J{\'a}nos M R{\'e}thelyi and Robert C. Ribble and Marcella Rietschel and Brien P. Riley and Mirella Ruggeri and Ulrich Schall and Thomas G. Schulze and Sibylle G. Schwab and Rodney J. Scott and Jianxin Shi and Engilbert Sigurdsson and Jeremy Silverman and Chris C. A. Spencer and K{\'a}ri Stef{\'a}nsson and Amy Strange and Eric Strengman and T. Scott Stroup and Jaana Suvisaari and Lars Terenius and Srinivasa Thirumalai and Johan H. Thygesen and Sally Timm and Draga Toncheva and Edwin J. C. G. van den Oord and Jim van Os and Ruud Van Winkel and Jan Herman Veldink and Dermot Walsh and August G. Wang and Durk Wiersma and Dieter B. Wildenauer and Hywel J. Williams and Nigel Melvillle Williams and Brandon K. Wormley and Stanley Zammit and Patrick F. Sullivan and Michael C. O’Donovan and Mark J. Daly and Pablo V. Gejman},
  journal={Nature Genetics},
  year={2011},
  volume={43},
  pages={969-976}
}
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… 

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References

SHOWING 1-10 OF 67 REFERENCES

Common variants on chromosome 6p22.1 are associated with schizophrenia

TLDR
It is demonstrated that common schizophrenia susceptibility alleles can be detected and the characterization of these signals will suggest important directions for research on susceptibility mechanisms.

Meta-analysis of genome-wide association studies identifies common variants associated with blood pressure variation in east Asians

TLDR
A meta-analysis of genome-wide association studies of systolic (SBP) and diastolic (DBP) blood pressure in 19,608 subjects of east Asian ancestry followed up with de novo genotyping and further replication in east Asian samples provides new insights into blood pressure regulation and potential targets for intervention.

Common variants conferring risk of schizophrenia

TLDR
Findings implicating the MHC region are consistent with an immune component to schizophrenia risk, whereas the association with NRGN and TCF4 points to perturbation of pathways involved in brain development, memory and cognition.

Genome-wide association defines more than 30 distinct susceptibility loci for Crohn's disease

TLDR
The results strongly confirm 11 previously reported loci and provide genome-wide significant evidence for 21 additional loci, including the regions containing STAT3, JAK2, ICOSLG, CDKAL1 and ITLN1, which offer promise for informed therapeutic development.

Genome-wide association study identifies eight loci associated with blood pressure

Elevated blood pressure is a common, heritable cause of cardiovascular disease worldwide. To date, identification of common genetic variants influencing blood pressure has proven challenging. We

Genome-wide association and meta-analysis of bipolar disorder in individuals of European ancestry

TLDR
Analysis of additional samples will be required to confirm that variant(s) in these regions influence BP risk, and these chromosomal regions harbor genes implicated in cell cycle, neurogenesis, neuroplasticity, and neurosignaling.

A family-based study of common polygenic variation and risk of schizophrenia

TLDR
Whether putative risk alleles from a case/control study tend to be over-transmitted to offspring with schizophrenia is asked, to exclude bias due to cryptic population stratification as a possible source of inflated type I error.

Identifying gene regulatory networks in schizophrenia

Integrating common and rare genetic variation in diverse human populations

TLDR
An expanded public resource of genome variants in global populations supports deeper interrogation of genomic variation and its role in human disease, and serves as a step towards a high-resolution map of the landscape of human genetic variation.

Association analyses of 249,796 individuals reveal 18 new loci associated with body mass index

TLDR
18 new loci associated with body mass index are identified, one of which includes a copy number variant near GPRC5B, and genes in other newly associated loci may provide new insights into human body weight regulation.
...