TY - JOUR
T1 - A highly significant association between a COMT haplotype and schizophrenia
AU - Shifman, Sagiv
AU - Bronstein, Michal
AU - Sternfeld, Meira
AU - Pisanté-Shalom, Anne
AU - Lev-Lehman, Efrat
AU - Weizman, Avraham
AU - Reznik, Ilya
AU - Spivak, Baruch
AU - Grisaru, Nimrod
AU - Karp, Leon
AU - Schiffer, Richard
AU - Kotler, Moshe
AU - Strous, Rael D.
AU - Swartz-Vanetik, Marnina
AU - Knobler, Haim Y.
AU - Shinar, Eilat
AU - Beckmann, Jacques S.
AU - Yakir, Benjamin
AU - Risch, Neil
AU - Zak, Naomi B.
AU - Darvasi, Ariel
PY - 2002/12/1
Y1 - 2002/12/1
N2 - Several lines of evidence have placed the catechol-O-methyltransferase (COMT) gene in the limelight as a candidate gene for schizophrenia. One of these is its biochemical function in metabolism of catecholamine neurotransmitters; another is the microdeletion, on chromosome 22q11, that includes the COMT gene and causes velocardiofacial syndrome, a syndrome associated with a high rate of psychosis, particularly schizophrenia. The interest in the COMT gene as a candidate risk factor for schizophrenia has led to numerous linkage and association analyses. These, however, have failed to produce any conclusive result. Here we report an efficient approach to gene discovery. The approach consists of (i) a large sample size - to our knowledge, the present study is the largest case-control study performed to date in schizophrenia; (ii) the use of Ashkenazi Jews, a well defined homogeneous population; and (iii) a stepwise procedure in which several single nucleotide polymorphisms (SNPs) are scanned in DNA pools, followed by individual genotyping and haplotype analysis of the relevant SNPs. We found a highly significant association between schizophrenia and a COMT haplotype (P = 9.5 × 10-8). The approach presented can be widely implemented for the genetic dissection of other common diseases.
AB - Several lines of evidence have placed the catechol-O-methyltransferase (COMT) gene in the limelight as a candidate gene for schizophrenia. One of these is its biochemical function in metabolism of catecholamine neurotransmitters; another is the microdeletion, on chromosome 22q11, that includes the COMT gene and causes velocardiofacial syndrome, a syndrome associated with a high rate of psychosis, particularly schizophrenia. The interest in the COMT gene as a candidate risk factor for schizophrenia has led to numerous linkage and association analyses. These, however, have failed to produce any conclusive result. Here we report an efficient approach to gene discovery. The approach consists of (i) a large sample size - to our knowledge, the present study is the largest case-control study performed to date in schizophrenia; (ii) the use of Ashkenazi Jews, a well defined homogeneous population; and (iii) a stepwise procedure in which several single nucleotide polymorphisms (SNPs) are scanned in DNA pools, followed by individual genotyping and haplotype analysis of the relevant SNPs. We found a highly significant association between schizophrenia and a COMT haplotype (P = 9.5 × 10-8). The approach presented can be widely implemented for the genetic dissection of other common diseases.
UR - http://www.scopus.com/inward/record.url?scp=0036913209&partnerID=8YFLogxK
U2 - 10.1086/344514
DO - 10.1086/344514
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C2 - 12402217
AN - SCOPUS:0036913209
SN - 0002-9297
VL - 71
SP - 1296
EP - 1302
JO - American Journal of Human Genetics
JF - American Journal of Human Genetics
IS - 6
ER -