A systematic association mapping on chromosome 6q in bipolar affective disorder - evidence for themelanin-concentrating-hormone-receptor-2gene as a risk factor for bipolar affective disorder

Abou Jamra, Rami, Schulze, Thomas G., Becker, Tim, Brockschmidt, Felix F., Green, Elaine Karen, Alblas, Margrieta A., Wendland, Jens R., Adli, Mazda, Grozeva, Detelina ORCID: https://orcid.org/0000-0003-3239-8415, Strohmeier, Jana, Georgi, Alexander, Craddock, Nicholas John ORCID: https://orcid.org/0000-0003-2171-0610, Propping, Peter, Rietschel, Marcella, Nöthen, Markus M., Cichon, Sven and Schumacher, Johannes 2009. A systematic association mapping on chromosome 6q in bipolar affective disorder - evidence for themelanin-concentrating-hormone-receptor-2gene as a risk factor for bipolar affective disorder. American Journal of Medical Genetics Part B: Neuropsychiatric Genetics 153B (4) , pp. 878-884. 10.1002/ajmg.b.31051

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Abstract

Strong evidence of linkage between chromosomal region 6q16-q22 and bipolar affective disorder (BPAD) has previously been reported. We conducted a systematic association mapping of the 6q-linkage interval using 617 SNP markers in a BPAD case–control sample of German descent (cases = 330, controls = 325). In this screening step, 46 SNPs showed nominally significant BPAD-association (P-values between 0.0007 and 0.0484). Although none of the 46 SNPs survived correction for multiple testing, they were genotyped in a second and ethnically matched BPAD sample (cases = 328, controls = 397). At the melanin-concentrating-hormone-receptor-2 (MCHR2) gene, we found nominal association in both the initial and second BPAD samples (combined P = 0.008). This finding was followed up by the genotyping of 17 additional MCHR2-SNPs in the combined sample in order to define our findings more precisely. We found that the MCHR2-locus can be divided into three different haplotype-blocks, and observed that the MCHR2-association was most pronounced in BPAD male patients with psychotic symptoms. In two neighboring blocks, putative risk-haplotypes were found to be 7% more frequent in patients (block II: 23.3% vs. 16.2%, P = 0.005, block III: 39.2% vs. 32.0%, P  = 0.024), whereas the putative protective haplotypes were found to be 5–8% less frequent in patients (block II: 11.6% vs. 16.4%, P = 0.041, block III: 30.0% vs. 38.8%, P = 0.007). The corresponding odds ratios (single-marker analysis) ranged between 1.25 and 1.46. Our findings may indicate that MCHR2 is a putative risk factor for BPAD. These findings should be interpreted with caution and replicated in independent BPAD samples.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Medicine MRC Centre for Neuropsychiatric Genetics and Genomics (CNGG)
Subjects:	Q Science > QH Natural history > QH426 Genetics R Medicine > R Medicine (General) R Medicine > RC Internal medicine > RC0321 Neuroscience. Biological psychiatry. Neuropsychiatry
Uncontrolled Keywords:	BPAD;GPR145;LD; genotype–phenotype analysis; MCHR2
Publisher:	Wiley-Blackwell
ISSN:	1552-4841
Last Modified:	05 Oct 2024 13:55
URI:	https://orca.cardiff.ac.uk/id/eprint/22145

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