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Modest evidence for linkage and possible confirmation of association between NOTCH4 and schizophrenia in a large veterans affairs cooperative study sample
Author(s) -
Skol A.D.,
Young K.A.,
Tsuang D.W.,
Faraone S.V.,
Haverstock S.L.,
Bingham S.,
Prabhudesai S.,
Mena F.,
Me A.S.,
Yu ChangEn,
Rundell Paul,
Pepple J.,
Sauter F.,
Baldwin C.,
Weiss D.,
Collins J.,
Keith T.,
Boehnke M.,
Schellenberg G.D.,
Tsuang M.T.
Publication year - 2002
Publication title -
american journal of medical genetics part b: neuropsychiatric genetics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.393
H-Index - 126
eISSN - 1552-485X
pISSN - 1552-4841
DOI - 10.1002/ajmg.b.10055
Subject(s) - schizoaffective disorder , schizophrenia (object oriented programming) , allele , haplotype , psychology , sibling , veterans affairs , psychosis , linkage (software) , genetics , psychiatry , biology , developmental psychology , gene , medicine
Wei and Hemmings [2000: Nat Genet 25:376–377], using 80 British parent–offspring trios, identified a number of NOTCH4 variants and haplotypes that showed statistically significant evidence of association to schizophrenia. Specifically, the 10 repeat allele of a (CTG) n marker and the 8 repeat allele of a (TAA) n marker demonstrated excess transmission to affected individuals; SNP21 and haplotypes SNP2‐(CTG) n and SNP12‐SNP2‐(CTG) n also showed significant associations. In an attempt to replicate these findings, we tested for linkage and association between the same five markers used by Wei and Hemmings in 166 families collected from a multi‐center study conducted by the Department of Veterans Affairs (DVA) Cooperative Study Program (CSP). The families include 392 affected subjects (schizophrenia or schizoaffective disorder, depressed) and 216 affected sibling pairs. The families represent a mix of European Americans (n = 62, 37%), African Americans (n = 60, 36%), and racially mixed or other races (n = 44, 27%). We identified moderate evidence for linkage in the pooled race sample (LOD = 1.25) and found excess transmission of the 8 ( P = 0.06) and 13 ( P = 0.04) repeat alleles of the (TAA) n marker to African American schizophrenic subjects. The 8 and 13 repeat alleles were previously identified to be positively associated with schizophrenia by Wei and Hemmings [2000: Nat Genet 25:376–377] and Sklar et al. [2001: Nat Genet 28:126–128], respectively. © 2003 Wiley‐Liss, Inc.