Title |
Genome-wide association study implicates NDST3 in schizophrenia and bipolar disorder
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Published in |
Nature Communications, November 2013
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DOI | 10.1038/ncomms3739 |
Pubmed ID | |
Authors |
Todd Lencz, Saurav Guha, Chunyu Liu, Jeffrey Rosenfeld, Semanti Mukherjee, Pamela DeRosse, Majnu John, Lijun Cheng, Chunling Zhang, Judith A. Badner, Masashi Ikeda, Nakao Iwata, Sven Cichon, Marcella Rietschel, Markus M. Nöthen, A.T.A. Cheng, Colin Hodgkinson, Qiaoping Yuan, John M. Kane, Annette T. Lee, Anne Pisanté, Peter K. Gregersen, Itsik Pe’er, Anil K. Malhotra, David Goldman, Ariel Darvasi |
Abstract |
Schizophrenia and bipolar disorder are major psychiatric disorders with high heritability and overlapping genetic variance. Here we perform a genome-wide association study in an ethnically homogeneous cohort of 904 schizophrenia cases and 1,640 controls drawn from the Ashkenazi Jewish population. We identify a novel genome-wide significant risk locus at chromosome 4q26, demonstrating the potential advantages of this founder population for gene discovery. The top single-nucleotide polymorphism (SNP; rs11098403) demonstrates consistent effects across 11 replication and extension cohorts, totalling 23, 191 samples across multiple ethnicities, regardless of diagnosis (schizophrenia or bipolar disorder), resulting in Pmeta=9.49 × 10(-12) (odds ratio (OR)=1.13, 95% confidence interval (CI): 1.08-1.17) across both disorders and Pmeta=2.67 × 10(-8) (OR=1.15, 95% CI: 1.08-1.21) for schizophrenia alone. In addition, this intergenic SNP significantly predicts postmortem cerebellar gene expression of NDST3, which encodes an enzyme critical to heparan sulphate metabolism. Heparan sulphate binding is critical to neurite outgrowth, axon formation and synaptic processes thought to be aberrant in these disorders. |
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Venezuela, Bolivarian Republic of | 1 | 2% |
Other | 1 | 2% |
Unknown | 26 | 57% |
Demographic breakdown
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Scientists | 6 | 13% |
Practitioners (doctors, other healthcare professionals) | 3 | 7% |
Science communicators (journalists, bloggers, editors) | 1 | 2% |
Mendeley readers
Geographical breakdown
Country | Count | As % |
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United Kingdom | 1 | <1% |
India | 1 | <1% |
United States | 1 | <1% |
Unknown | 128 | 98% |
Demographic breakdown
Readers by professional status | Count | As % |
---|---|---|
Student > Ph. D. Student | 27 | 21% |
Researcher | 22 | 17% |
Student > Master | 12 | 9% |
Other | 11 | 8% |
Student > Bachelor | 9 | 7% |
Other | 24 | 18% |
Unknown | 26 | 20% |
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Biochemistry, Genetics and Molecular Biology | 20 | 15% |
Medicine and Dentistry | 16 | 12% |
Neuroscience | 12 | 9% |
Psychology | 4 | 3% |
Other | 15 | 11% |
Unknown | 36 | 27% |