Gene-wide analyses of genome-wide association data sets: evidence for multiple common risk alleles for schizophrenia and bipolar disorder and for ... View Full Text


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Article Info

DATE

2009-03

AUTHORS

V Moskvina, N Craddock, P Holmans, I Nikolov, J S Pahwa, E Green, M J Owen, M C O'Donovan

ABSTRACT

Genome-wide association (GWAS) analyses have identified susceptibility loci for many diseases, but most risk for any complex disorder remains unattributed. There is therefore scope for complementary approaches to these data sets. Gene-wide approaches potentially offer additional insights. They might identify association to genes through multiple signals. Also, by providing support for genes rather than single nucleotide polymorphisms (SNPs), they offer an additional opportunity to compare the results across data sets. We have undertaken gene-wide analysis of two GWAS data sets: schizophrenia and bipolar disorder. We performed two forms of analysis, one based on the smallest P-value per gene, the other on a truncated product of P method. For each data set and at a range of statistical thresholds, we observed significantly more SNPs within genes (P(min) for excess<0.001) showing evidence for association than expected whereas this was not true for extragenic SNPs (P(min) for excess>0.1). At a range of thresholds of significance, we also observed substantially more associated genes than expected (P(min) for excess in schizophrenia=1.8 x 10(-8), in bipolar=2.4 x 10(-6)). Moreover, an excess of genes showed evidence for association across disorders. Among those genes surpassing thresholds highly enriched for true association, we observed evidence for association to genes reported in other GWAS data sets (CACNA1C) or to closely related family members of those genes including CSF2RB, CACNA1B and DGKI. Our analyses show that association signals are enriched in and around genes, large numbers of genes contribute to both disorders and gene-wide analyses offer useful complementary approaches to more standard methods. More... »

PAGES

252

References to SciGraph publications

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  • 2008-02. A genome-wide association study implicates diacylglycerol kinase eta (DGKH) and several other genes in the etiology of bipolar disorder in MOLECULAR PSYCHIATRY
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  • 2008-05. Meta-analysis of genome-wide association data and large-scale replication identifies additional susceptibility loci for type 2 diabetes in NATURE GENETICS
  • 2008-10. Association study of CSF2RB with schizophrenia in Irish family and case – control samples in MOLECULAR PSYCHIATRY
  • 2005-12. Theories of schizophrenia: a genetic-inflammatory-vascular synthesis in BMC MEDICAL GENETICS
  • 2008-09-11. Large recurrent microdeletions associated with schizophrenia in NATURE
  • 1995-01. Polymerase δ variants in RER colorectal tumours in NATURE GENETICS
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  • Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1038/mp.2008.133

    DOI

    http://dx.doi.org/10.1038/mp.2008.133

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1010935179

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/19065143


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