Collaborative genome-wide association analysis supports a role for ANK3 and CACNA1C in bipolar disorder

@article{Ferreira2008CollaborativeGA,
  title={Collaborative genome-wide association analysis supports a role for ANK3 and CACNA1C in bipolar disorder},
  author={Manuel A. R. Ferreira and Michael C. O'Donovan and Yan A. Meng and Ian R Jones and Douglas M. Ruderfer and Lisa Jones and Jinbo Fan and George Kirov and Roy H. Perlis and Elaine K Green and Jordan W. Smoller and Detelina Grozeva and Jennifer L. Stone and Ivan Nikolov and Kimberly Chambert and Marian L. Hamshere and Vishwajit L. Nimgaonkar and Valentina Moskvina and Michael E. Thase and Sian Caesar and Gary S. Sachs and Jennifer Franklin and Katherine Gordon-Smith and Kristin G. Ardlie and S. Gabriel and Christine Fraser and Brendan Blumenstiel and Matthew Defelice and Gerome D. Breen and Michael Gill and Derek W. Morris and Amanda Elkin and Walter J. Muir and Kevin A. McGhee and Richard J. Williamson and Donald J. Macintyre and Alan W Maclean and David M. St. Clair and Michelle Robinson and Margaret Van Beck and Ana C P Pereira and Radhika Kandaswamy and Andrew McQuillin and David A. Collier and Nicholas J Bass and Allan H. Young and Jacob Lawrence and I. Nicol Ferrier and Adebayo Anjorin and Anne Farmer and David Curtis and Edward M. Scolnick and Peter McGuffin and Mark J. Daly and Aiden P. Corvin and Peter A Holmans and Douglas H.R. Blackwood and Hugh M D Gurling and Michael J. Owen and Shaun M Purcell and Pamela Sklar and Nick Craddock},
  journal={Nature Genetics},
  year={2008},
  volume={40},
  pages={1056-1058}
}
To identify susceptibility loci for bipolar disorder, we tested 1.8 million variants in 4,387 cases and 6,209 controls and identified a region of strong association (rs10994336, P = 9.1 × 10−9) in ANK3 (ankyrin G). We also found further support for the previously reported CACNA1C (alpha 1C subunit of the L-type voltage-gated calcium channel; combined P = 7.0 × 10−8, rs1006737). Our results suggest that ion channelopathies may be involved in the pathogenesis of bipolar disorder. 
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References

SHOWING 1-10 OF 40 REFERENCES
Whole-genome association study of bipolar disorder
TLDR
A comparison of the strongest associations with the genome-wide scan of 1868 patients with BP disorder and 2938 controls who completed the scan as part of the Wellcome Trust Case–Control Consortium indicates concordant signals for SNPs within the voltage-dependent calcium channel, L-type, alpha 1C subunit (CACNA1C) gene. Expand
A genome-wide association study implicates diacylglycerol kinase eta (DGKH) and several other genes in the etiology of bipolar disorder
TLDR
This first genome-wide association study of bipolar disorder shows that several genes, each of modest effect, reproducibly influence disease risk and may be a polygenic disease. Expand
Genome-wide association study of 14,000 cases of seven common diseases and 3,000 shared controls
TLDR
This study has demonstrated that careful use of a shared control group represents a safe and effective approach to GWA analyses of multiple disease phenotypes; generated a genome-wide genotype database for future studies of common diseases in the British population; and shown that, provided individuals with non-European ancestry are excluded, the extent of population stratification in theBritish population is generally modest. Expand
Genome-wide association study identifies new susceptibility loci for Crohn disease and implicates autophagy in disease pathogenesis
TLDR
It is demonstrated that ATG16L1 is expressed in intestinal epithelial cell lines and that functional knockdown of this gene abrogates autophagy of Salmonella typhimurium, and these findings suggest thatAutophagy and host cell responses to intracellular microbes are involved in the pathogenesis of Crohn disease. Expand
Genome-Wide Association Analysis Identifies Loci for Type 2 Diabetes and Triglyceride Levels
TLDR
The discovery of associated variants in unsuspected genes and outside coding regions illustrates the ability of genome-wide association studies to provide potentially important clues to the pathogenesis of common diseases. Expand
Ion Channel Functional Candidate Genes in Multigenic Neuropsychiatric Disease
  • J. Gargus
  • Medicine, Biology
  • Biological Psychiatry
  • 2006
TLDR
Ex extrapolation from the cardiac (Long QT] and muscle (Periodic Paralysis) channelopathy syndromes provides a simplified predictive framework of molecular pathology, and KCNN3 is explored as a paradigm to consider. Expand
Genome-wide association study identifies a second prostate cancer susceptibility variant at 8q24
TLDR
A second genetic variant in the 8q24 region that, in conjunction with another variant recently discovered, accounts for about 11%–13% of prostate cancer cases in individuals of European descent and 31% of cases in African Americans is reported. Expand
Genomic control for association studies.
TLDR
The performance of the genomic control method is quite good for plausible effects of liability genes, which bodes well for future genetic analyses of complex disorders. Expand
A haplotype map of the human genome
TLDR
A public database of common variation in the human genome: more than one million single nucleotide polymorphisms for which accurate and complete genotypes have been obtained in 269 DNA samples from four populations, including ten 500-kilobase regions in which essentially all information about common DNA variation has been extracted. Expand
The familial transmission of bipolar illness.
TLDR
As part of the National Institute of Mental Health Collaborative Program on the Psychobiology of Depression study, data were collected on 2225 first-degree relatives of 612 probands and the mixed model, which allows for a single major locus with a multifactorial background, gave evidence for the presence of amajor locus when controlling for the effects of birth cohort and age at onset. Expand
...
1
2
3
4
...