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Genome-wide association study identifies genetic variation in neurocan as a susceptibility factor for bipolar disorder.
Am. J. Hum. Genet. 88, 372-381 (2011)
We conducted a genome-wide association study (GWAS) and a follow-up study of bipolar disorder (BD), a common neuropsychiatric disorder. In the GWAS, we investigated 499,494 autosomal and 12,484 X-chromosomal SNPs in 682 patients with BD and in 1300 controls. In the first follow-up step, we tested the most significant 48 SNPs in 1729 patients with BD and in 2313 controls. Eight SNPs showed nominally significant association with BD and were introduced to a meta-analysis of the GWAS and the first follow-up samples. Genetic variation in the neurocan gene (NCAN) showed genome-wide significant association with BD in 2411 patients and 3613 controls (rs1064395, p = 3.02 × 10(-8); odds ratio = 1.31). In a second follow-up step, we replicated this finding in independent samples of BD, totaling 6030 patients and 31,749 controls (p = 2.74 × 10(-4); odds ratio = 1.12). The combined analysis of all study samples yielded a p value of 2.14 × 10(-9) (odds ratio = 1.17). Our results provide evidence that rs1064395 is a common risk factor for BD. NCAN encodes neurocan, an extracellular matrix glycoprotein, which is thought to be involved in cell adhesion and migration. We found that expression in mice is localized within cortical and hippocampal areas. These areas are involved in cognition and emotion regulation and have previously been implicated in BD by neuropsychological, neuroimaging, and postmortem studies.
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Publikationstyp
Artikel: Journalartikel
Dokumenttyp
Wissenschaftlicher Artikel
Schlagwörter
Chonroitin sulfate proteoglycan; Diagnostic interview; Procedural validity; Risk-factors; Brain; Metaanalysis; Rationale; Individuals; Reliability; Disease
ISSN (print) / ISBN
0002-9297
e-ISSN
1537-6605
Zeitschrift
American Journal of Human Genetics, The
Quellenangaben
Band: 88,
Heft: 3,
Seiten: 372-381
Verlag
Elsevier
Verlagsort
New York, NY
Begutachtungsstatus
Peer reviewed
Institut(e)
Institute of Genetic Epidemiology (IGE)