TY - JOUR
T1 - The NOTCH4 locus and schizophrenia
T2 - Analyses in the german and palestinian Arab population
AU - Cichon, S.
AU - Schumacher, J.
AU - Ivo, R.
AU - Macchiardi, F.
AU - Schulze, T. G.
AU - Müller, D. J.
AU - Kremer, I.
AU - Dobrusin, M.
AU - Mujaheed, M.
AU - Murad, I.
AU - Blanaru, M.
AU - Bannoura, I.
AU - Reshef, A.
AU - Bachner-Melman, R.
AU - Belmaker, R. H.
AU - Ebstein, R. P.
AU - Maier, W.
AU - Rietschel, M.
AU - Propping, P.
AU - Nöthen, M. M.
PY - 2001/10/8
Y1 - 2001/10/8
N2 - Recently, the NOTCH4 locus on chromosomal region 6p has been reported to be associated with schizophrenia in the British population [Wei & Hemmings, Nature Genet. 25: 376-377 (2000)]. In order to replicate this finding in independent schizophrenia samples, we examined four variants [(TAA)n repeat, SNP1, SNP2, (CTG)n repeat] in the 5′-flanking region and in the coding region of the NOTCH4 gene in 159 parent-offspring trio samples of German and 209 of Palestinian Arab descent. TDT analysis revealed significant linkage disequilibrium (LD) of schizophrenia with the (TAA)n repeat in the Palestinian Arab sample (P = 0.0082) and a borderline significant trend in the German sample (P = 0.0547). In addition, two distinct four-marker haplotypes displayed association in the German (P = 0.0038) and Palestinian Arab (P = 0.0111 ) trio samples. The observation of different associated alleles and haplotypes in the populations studied by Wei & Hemmings and our group may be explained by the existence of a so far unknown functional variant at the NOTCH4 locus involved in the development of schizophrenia. Therefore, we sought for additional variants using SSCA. We identified nine SNPs that are currently tested for association with schizophrenia in the German and Palestinian Arab samples.
AB - Recently, the NOTCH4 locus on chromosomal region 6p has been reported to be associated with schizophrenia in the British population [Wei & Hemmings, Nature Genet. 25: 376-377 (2000)]. In order to replicate this finding in independent schizophrenia samples, we examined four variants [(TAA)n repeat, SNP1, SNP2, (CTG)n repeat] in the 5′-flanking region and in the coding region of the NOTCH4 gene in 159 parent-offspring trio samples of German and 209 of Palestinian Arab descent. TDT analysis revealed significant linkage disequilibrium (LD) of schizophrenia with the (TAA)n repeat in the Palestinian Arab sample (P = 0.0082) and a borderline significant trend in the German sample (P = 0.0547). In addition, two distinct four-marker haplotypes displayed association in the German (P = 0.0038) and Palestinian Arab (P = 0.0111 ) trio samples. The observation of different associated alleles and haplotypes in the populations studied by Wei & Hemmings and our group may be explained by the existence of a so far unknown functional variant at the NOTCH4 locus involved in the development of schizophrenia. Therefore, we sought for additional variants using SSCA. We identified nine SNPs that are currently tested for association with schizophrenia in the German and Palestinian Arab samples.
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M3 - Article
AN - SCOPUS:0347079326
SN - 1552-4841
VL - 105
SP - 571
JO - American Journal of Medical Genetics, Part B: Neuropsychiatric Genetics
JF - American Journal of Medical Genetics, Part B: Neuropsychiatric Genetics
IS - 7
ER -