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

Rami Abou Jamra, Thomas G. Schulze, Tim Becker, Felix F. Brockschmidt, Elaine Green, Margrieta A. Alblas, Jens R. Wendland, Mazda Adli, Detelina Grozeva, Jana Strohmeier, Alexander Georgi, Nick Craddock, Peter Propping, Marcella Rietschel, Markus M. Nöthen, Sven Cichon, Johannes Schumacher

Research output: Contribution to journalArticle

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 signifi-cant 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.

Original languageEnglish (US)
Pages (from-to)878-884
Number of pages7
JournalAmerican Journal of Medical Genetics - Neuropsychiatric Genetics
Volume153
Issue number4
DOIs
StatePublished - Jun 2010
Externally publishedYes

Fingerprint

Chromosome Mapping
Mood Disorders
Bipolar Disorder
Genes
Single Nucleotide Polymorphism
Haplotypes
melanin-concentrating hormone receptor
Odds Ratio

Keywords

  • BPAD
  • Genotype-phenotype analysis
  • GPR145
  • LD
  • MCHR2

ASJC Scopus subject areas

  • Genetics(clinical)
  • Psychiatry and Mental health
  • Cellular and Molecular Neuroscience

Cite this

A systematic association mapping on chromosome 6q in bipolar affective disorder - Evidence for the melanin-concentrating-hormone-receptor-2 gene as a risk factor for bipolar affective disorder. / Jamra, Rami Abou; Schulze, Thomas G.; Becker, Tim; Brockschmidt, Felix F.; Green, Elaine; Alblas, Margrieta A.; Wendland, Jens R.; Adli, Mazda; Grozeva, Detelina; Strohmeier, Jana; Georgi, Alexander; Craddock, Nick; Propping, Peter; Rietschel, Marcella; Nöthen, Markus M.; Cichon, Sven; Schumacher, Johannes.

In: American Journal of Medical Genetics - Neuropsychiatric Genetics, Vol. 153, No. 4, 06.2010, p. 878-884.

Research output: Contribution to journalArticle

Jamra, RA, Schulze, TG, Becker, T, Brockschmidt, FF, Green, E, Alblas, MA, Wendland, JR, Adli, M, Grozeva, D, Strohmeier, J, Georgi, A, Craddock, N, Propping, P, Rietschel, M, Nöthen, MM, Cichon, S & Schumacher, J 2010, 'A systematic association mapping on chromosome 6q in bipolar affective disorder - Evidence for the melanin-concentrating-hormone-receptor-2 gene as a risk factor for bipolar affective disorder', American Journal of Medical Genetics - Neuropsychiatric Genetics, vol. 153, no. 4, pp. 878-884. https://doi.org/10.1002/ajmg.b.31051
Jamra, Rami Abou ; Schulze, Thomas G. ; Becker, Tim ; Brockschmidt, Felix F. ; Green, Elaine ; Alblas, Margrieta A. ; Wendland, Jens R. ; Adli, Mazda ; Grozeva, Detelina ; Strohmeier, Jana ; Georgi, Alexander ; Craddock, Nick ; Propping, Peter ; Rietschel, Marcella ; Nöthen, Markus M. ; Cichon, Sven ; Schumacher, Johannes. / A systematic association mapping on chromosome 6q in bipolar affective disorder - Evidence for the melanin-concentrating-hormone-receptor-2 gene as a risk factor for bipolar affective disorder. In: American Journal of Medical Genetics - Neuropsychiatric Genetics. 2010 ; Vol. 153, No. 4. pp. 878-884.
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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 signifi-cant 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.",
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AU - Jamra, Rami Abou

AU - Schulze, Thomas G.

AU - Becker, Tim

AU - Brockschmidt, Felix F.

AU - Green, Elaine

AU - Alblas, Margrieta A.

AU - Wendland, Jens R.

AU - Adli, Mazda

AU - Grozeva, Detelina

AU - Strohmeier, Jana

AU - Georgi, Alexander

AU - Craddock, Nick

AU - Propping, Peter

AU - Rietschel, Marcella

AU - Nöthen, Markus M.

AU - Cichon, Sven

AU - Schumacher, Johannes

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