Analysis of coding-polymorphisms in NOTCH-related genes reveals NUMBL poly-glutamine repeat to be associated with schizophrenia in Brazilian and Danish subjects

TY - JOUR

T1 - Analysis of coding-polymorphisms in NOTCH-related genes reveals NUMBL poly-glutamine repeat to be associated with schizophrenia in Brazilian and Danish subjects

AU - Passos Gregorio, Sheila

AU - Gattaz, Wagner F

AU - Tavares, Hildeberto

AU - Kieling, Christian

AU - Timm, Sally

AU - Wang, August G

AU - Berg Rasmussen, Henrik

AU - Werge, Thomas

AU - Dias-Neto, Emmanuel

PY - 2006

Y1 - 2006

N2 - Abnormality in neurodevelopment is one of the most robust hypotheses on the etiology of schizophrenia and has found substantial support from brain imaging and genetic studies. Neurodevelopmental processes involve several signaling pathways, including the Notch, but little is known at present regarding their possible involvement in schizophrenia. In the present study we investigated the link of non-synonymous variants of five genes of the Notch pathway (NOTCH2, NOTCH3, JAGGED2, ASCL1 and NUMBL) to schizophrenia in a group of 200 Brazilian patients and 200-paired controls. Also, we replicated the association of the NUMBL variant, our most promising finding, in an unrelated set of 684 Danish patients and controls. When the Brazilian and Danish cohorts were merged, a total of 1084 subjects, we found the allele 18 CAG of NUMBL (p=0.003, x2=8.88, OR=1.30, 95% CI 1.09-1.56) as well as the 18/18 CAG genotype (p=0.002, x2=9.46, OR=1.46, 95% CI 1.15-1.87) to be associated with schizophrenia. The consistency of this finding in two independent and unrelated populations reinforces the veracity of this association.

AB - Abnormality in neurodevelopment is one of the most robust hypotheses on the etiology of schizophrenia and has found substantial support from brain imaging and genetic studies. Neurodevelopmental processes involve several signaling pathways, including the Notch, but little is known at present regarding their possible involvement in schizophrenia. In the present study we investigated the link of non-synonymous variants of five genes of the Notch pathway (NOTCH2, NOTCH3, JAGGED2, ASCL1 and NUMBL) to schizophrenia in a group of 200 Brazilian patients and 200-paired controls. Also, we replicated the association of the NUMBL variant, our most promising finding, in an unrelated set of 684 Danish patients and controls. When the Brazilian and Danish cohorts were merged, a total of 1084 subjects, we found the allele 18 CAG of NUMBL (p=0.003, x2=8.88, OR=1.30, 95% CI 1.09-1.56) as well as the 18/18 CAG genotype (p=0.002, x2=9.46, OR=1.46, 95% CI 1.15-1.87) to be associated with schizophrenia. The consistency of this finding in two independent and unrelated populations reinforces the veracity of this association.

U2 - 10.1016/j.schres.2006.06.036

DO - 10.1016/j.schres.2006.06.036

M3 - Journal article

SN - 0920-9964

VL - 88

SP - 275

EP - 282

JO - Schizophrenia Research

JF - Schizophrenia Research

IS - 1-3

ER -