title: 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.
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.
authors.affiliation: Institute of Human Genetics, University of Bonn, Bonn, Germany. rami.aboujamra@uni-bonn.de
authors.forename: Rami
authors.initials: R
authors.lastname: Abou Jamra
authors.forename: Thomas G
authors.initials: TG
authors.lastname: Schulze
authors.forename: Tim
authors.initials: T
authors.lastname: Becker
authors.forename: Felix F
authors.initials: FF
authors.lastname: Brockschmidt
authors.forename: Elaine
authors.initials: E
authors.lastname: Green
authors.forename: Margrieta A
authors.initials: MA
authors.lastname: Alblas
authors.forename: Jens R
authors.initials: JR
authors.lastname: Wendland
authors.forename: Mazda
authors.initials: M
authors.lastname: Adli
authors.forename: Detelina
authors.initials: D
authors.lastname: Grozeva
authors.forename: Jana
authors.initials: J
authors.lastname: Strohmeier
authors.forename: Alexander
authors.initials: A
authors.lastname: Georgi
authors.forename: Nick
authors.initials: N
authors.lastname: Craddock
authors.forename: Peter
authors.initials: P
authors.lastname: Propping
authors.forename: Marcella
authors.initials: M
authors.lastname: Rietschel
authors.forename: Markus M
authors.initials: MM
authors.lastname: Nöthen
authors.forename: Sven
authors.initials: S
authors.lastname: Cichon
authors.forename: Johannes
authors.initials: J
authors.lastname: Schumacher
mesh_terms: D000328:Adult; D000341:Affective Disorders, Psychotic / Q000235:genetics*; D001714:Bipolar Disorder / Q000235:genetics*; D016022:Case-Control Studies; D002875:Chromosomes; D005260:Female; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors; D044465:White People / Q000235:genetics