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Family-Based Association Study of Neuregulin 1 With Psychotic Bipolar Disorder
Journal article   Peer reviewed

Family-Based Association Study of Neuregulin 1 With Psychotic Bipolar Disorder

Fernando S Goes, Virginia L Willour, Peter P Zandi, Pamela L Belmonte, Dean F MacKinnon, Francis M Mondimore, Barbara Schweizer, Elliot S Gershon, Francis J McMahon and James B Potash
American journal of medical genetics. Part B, Neuropsychiatric genetics, Vol.150B(5), pp.693-702
07/05/2009
DOI: 10.1002/ajmg.b.30895
PMCID: PMC4026923
PMID: 19127563
url
http://doi.org/10.1002/ajmg.b.30895View
Open Access

Abstract

The Neuregulin 1 gene (\nNRG1\n) has been associated with schizophrenia, and, to a lesser extent, with bipolar disorder (BP). We investigated the association of\nNRG1\nwith BP in a large family sample, and then performed analyses according to the presence of psychotic features or mood-incongruent psychotic features. We genotyped 116 tagSNPs and four Icelandic “core” SNPs in 1,199 subjects from 314 nuclear families. Of 515 BP offspring, 341 had psychotic features, and 103 had mood-incongruent psychotic features. In single-marker and sliding window haplotype analyses using FBAT, there was little association using the standard BP or mood-incongruent psychotic BP phenotypes, but stronger signals were seen in the psychotic BP phenotype. The most significant associations with psychotic BP were in haplotypes within the 5′ “core” region. The strongest global\nP\n-value was across three SNPs: NRG241930-NRG243177-rs7819063 (\nP\n=0.0016), with an undertransmitted haplotype showing an individual\nP\n=0.0007. The most significant individual haplotype was an undertransmitted two-allele subset of the above (NRG243177-rs7819063,\nP\n=0.0004). Additional associations with psychotic BP were found across six SNPs in a 270 kb central region of the gene. The most 3′ of these, rs7005606 (\nP\n=0.0029), is located ∼4 kb from the type I\nNRG1\nisoform promoter. In sum, our study suggests that\nNRG1\nmay be specifically associated with the psychotic subset of BP; however, our results should be interpreted cautiously since they do not meet correction for multiple testing and await independent replication.
Psychosis mood-incongruent psychosis genetic association bipolar disorder Neuregulin 1

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