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Meta-analysis of two genome-wide association studies of bipolar disorder reveals important points of agreement

Molecular Psychiatry volume 13, pages 466–467 (2008)Cite this article

Two genome-wide association studies (GWAS) of bipolar disorder have been published to date, one in this journal1 and one in Nature.2 Cursory consideration of the top findings in the two studies does not show obvious overlap; some may even have concluded that there is no agreement. Yet, simulations show that true positive findings have only a 26% chance of falling into the top 1000 P-values in a GWAS, even when power to detect is 85%.3 We wish to draw attention to the need to look in-depth at GWAS data sets, rather than focusing simply on ‘top hits’. Closer analysis reveals several points of agreement between the two bipolar disorder GWAS published so far.

The Baum et al.1 study used the Illumina HumanHap550 platform to screen pooled DNA from two independent samples totaling 1233 bipolar I cases and 1439 matched controls. Baum et al.1 reported 88 single-nucleotide polymorphisms (SNPs) near 80 distinct genes that met replication criteria in both samples. The WTCCC study used the Affymetrix 500 k platform to individually genotype 1838 bipolar cases and 2938 controls.2 The WTCCC reported 14 SNPs associated with bipolar disorder at P<10−5. The use of different, largely non-overlapping genotyping platforms between these two studies restrict current comparisons to the imputed HapMap genotypes generated from the WTCCC data set, which have been shown to be very reliable.2 A total of 407 875 SNPs present on the Illumina HumanHap550 platform exceeded a minor allele frequency threshold of 5% and had <50% estimated missing data in the imputed data. We will refer to this as the ‘total imputation data set.’ Because Baum et al.1 did not individually genotype most SNPs, this set was compared to a total of 80 SNPs that have now been genotyped individually in at least one of the Baum et al. study samples.

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Acknowledgements

AB and FJM are supported by the NIMH Intramural Research Program. MH, EG and NC are funded by the Wellcome Trust and the UK Medical Research Council. SC, MR and MMN are funded by the National Genomic Network of the ‘Bundesministerium für Bildung und Forschung’, and MMN received support from the Alfried Krupp von Bohlen und Halbach-Stiftung.

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Authors and Affiliations

  1. US Department of Health and Human Services, Unit on the Genetic Basis of Mood and Anxiety Disorders, Mood and Anxiety Disorders Program, National Institute of Mental Health, National Institutes of Health, Bethesda, MD, USA

    A E Baum & F J McMahon

  2. Biostatistics and Bioinformatics Unit, School of Medicine, Cardiff University, Cardiff, UK

    M Hamshere

  3. Department of Psychological Medicine, School of Medicine, Cardiff University, Cardiff, UK

    M Hamshere, E Green & N Craddock

  4. Department of Genomics, Life and Brain Center, University of Bonn, Bonn, Germany

    S Cichon & M M Noethen

  5. Institute of Human Genetics, University of Bonn, Bonn, Germany

    S Cichon & M M Noethen

  6. Department of Genetic Epidemiology, Central Institute of Mental Health, University of Heidelberg, Mannheim, Germany. E-mail: bauma@mail.nih.gov,

    M Rietschel

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  1. A E Baum
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  3. E Green
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  8. F J McMahon
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Supplementary Information accompanies the paper on the Molecular Psychiatry website (http://www.nature.com/mp)

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Baum, A., Hamshere, M., Green, E. et al. Meta-analysis of two genome-wide association studies of bipolar disorder reveals important points of agreement. Mol Psychiatry 13, 466–467 (2008). https://doi.org/10.1038/mp.2008.16

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