Large-scale genome-wide association analysis of bipolar disorder identifies a new susceptibility locus near ODZ4

Pamela Sklar, Stephan Ripke, Laura J. Scott, Ole A. Andreassen, Sven Cichon, Nick Craddock, Howard J. Edenberg, John I. Nurnberger, Marcella Rietschel, Douglas Blackwood, Aiden Corvin, Matthew Flickinger, Weihua Guan, Morten Mattingsdal, Andrew McQuillin, Phoenix Kwan, Thomas F. Wienker, Mark Daly, Frank Dudbridge, Peter A. HolmansDanyu Lin, Margit Burmeister, Tiffany A. Greenwood, Marian L. Hamshere, Pierandrea Muglia, Erin N. Smith, Peter P. Zandi, Caroline M. Nievergelt, Rebecca McKinney, Paul D. Shilling, Nicholas J. Schork, Cinnamon S. Bloss, Tatiana Foroud, Daniel L. Koller, Elliot S. Gershon, Chunyu Liu, Judith A. Badner, William A. Scheftner, William B. Lawson, Evaristus A. Nwulia, Maria Hipolito, William Coryell, John Rice, William Byerley, Francis J. McMahon, Thomas G. Schulze, Keith Matthews, Jennifer Moran, Andrew McIntosh, Psychiat GWAS Consortium Bipolar D

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    1076 Citations (Scopus)

    Abstract

    We conducted a combined genome-wide association study (GWAS) of 7,481 individuals with bipolar disorder (cases) and 9,250 controls as part of the Psychiatric GWAS Consortium. Our replication study tested 34 SNPs in 4,496 independent cases with bipolar disorder and 42,422 independent controls and found that 18 of 34 SNPs had P < 0.05, with 31 of 34 SNPs having signals with the same direction of effect (P = 3.8 x 10(-7)). An analysis of all 11,974 bipolar disorder cases and 51,792 controls confirmed genome-wide significant evidence of association for CACNA1C and identified a new intronic variant in ODZ4. We identified a pathway comprised of subunits of calcium channels enriched in bipolar disorder association intervals. Finally, a combined GWAS analysis of schizophrenia and bipolar disorder yielded strong association evidence for SNPs in CACNA1C and in the region of NEK4-ITIH1-ITIH3-ITIH4. Our replication results imply that increasing sample sizes in bipolar disorder will confirm many additional loci.

    Original languageEnglish
    Pages (from-to)977-983
    Number of pages7
    JournalNature Genetics
    Volume43
    Issue number10
    DOIs
    Publication statusPublished - Oct 2011

    Keywords

    • PSYCHIATRIC-DISORDERS
    • SCHIZOPHRENIA
    • INDIVIDUALS
    • CACNA1C
    • RISK
    • PSYCHOSIS
    • GENETICS
    • ANK3

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