TY - JOUR
T1 - 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
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
PY - 2010/6
Y1 - 2010/6
N2 - 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.
AB - 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.
KW - BPAD
KW - Genotype-phenotype analysis
KW - GPR145
KW - LD
KW - MCHR2
UR - http://www.scopus.com/inward/record.url?scp=77952693605&partnerID=8YFLogxK
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U2 - 10.1002/ajmg.b.31051
DO - 10.1002/ajmg.b.31051
M3 - Article
C2 - 19927306
AN - SCOPUS:77952693605
SN - 1552-4841
VL - 153
SP - 878
EP - 884
JO - American Journal of Medical Genetics - Neuropsychiatric Genetics
JF - American Journal of Medical Genetics - Neuropsychiatric Genetics
IS - 4
ER -