Allelic association, DNA resequencing and copy number variation at the metabotropic glutamate receptor GRM7 gene locus in bipolar disorder. Issue 4 (8th May 2014)

• Record Type: Journal Article
• Authors: Kandaswamy, Radhika; McQuillin, Andrew; Curtis, David; Gurling, Hugh
• Is Part Of: American journal of medical genetics. Volume 165:Issue 4(2014)
• Page Start: 365
• Page End: 372
• Publication Date: 2014-05-08
• Subjects: Neuropsychiatry -- Periodicals; Medical genetics -- Periodicals; 616.8904205
• DOI: 10.1002/ajmg.b.32239
• Languages: English
• ISSNs: 1552-4841

Abstract

<abstract abstract-type="main"> <title> <x xml:space="preserve">Abstract</x> </title> <sec id="ajmgb32239-sec-0001" sec-type="section"> <p>Genetic markers at the <italic>GRM7</italic> gene have shown allelic association with bipolar disorder (BP) in several case–control samples including our own sample. In this report, we present results of resequencing the <italic>GRM7</italic> gene in 32 bipolar samples and 32 random controls selected from 553 bipolar cases and 547 control samples (UCL1). Novel and potential etiological base pair changes discovered by resequencing were genotyped in the entire UCL case–control sample. We also report on the association between <italic>GRM7</italic> and BP in a second sample of 593 patients and 642 controls (UCL2). The three most significantly associated SNPs in the original UCL1 BP GWAS sample were genotyped in the UCL2 sample, of which none were associated. After combining the genotype data for the two samples only two (rs1508724 and rs6769814) of the original three SNP markers remained significantly associated with BP. DNA sequencing revealed mutations in three cases which were absent in control subjects. A 3′‐UTR SNP rs56173829 was found to be significantly associated with BP in the whole UCL sample (<italic>P</italic> = 0.035; OR = 0.482), the rare allele being less common in cases compared to controls. Bioinformatic analyses predicted a change in the centroid secondary structure of RNA and alterations in the miRNA binding sites for the mutated base of rs56173829. We also validated two deletions and a duplication within <italic>GRM7</italic> using quantitative‐PCR which provides further support for the pre‐existing evidence that copy number variants at <italic>GRM7</italic> may have a role in the etiology of BP. © 2014 The Authors. American Journal of Medical Genetics Part B: Neuropsychiatric Published by Wiley Periodicals, Inc.</p> </sec> </abstract>