Background
The marker D1S251 of chromosome 1q42.1 showed significant association with schizophrenia
in a Taiwanese sample. We used single nucleotide polymorphism (SNP) fine mapping to
search for the vulnerability genes of schizophrenia.
Methods
We selected 120 SNPs covering 1 Mb around D1S251 from the public database. These selected
SNPs were initially validated if allele frequency was >10%. Forty-seven validated
SNPs were genotyped in 102 families with at least 2 siblings affected with schizophrenia.
Results
Two SNP blocks showed significant association with schizophrenia. Block 1 (five-SNP),
located between intron 2 and intron 13 of the glyceronephosphate O-acyltransferase
(GNPAT) gene, showed the most significant associations using single-locus TDT (z = −2.07, p = .038, df = 1) and haplotype association analyses (z = −1.99, p = .046, df = 1). Block 2 (two-SNP), located between intron 4 and intron 5 of the disrupted-in-schizophrenia
1 (DISC1) gene, also showed the most significant results in both the single-locus (z = −3.22, p = .0013, df = 1) and haplotype association analyses (z = 3.35, p = .0008, df = 1). The association of the DISC1 gene with schizophrenia was mainly in the patient
group with sustained attention deficits as assessed by the Continuous Performance
Test.
Conclusions
Chromosome 1q42.1 harbors GNPAT and DISC1 as candidate genes for schizophrenia, and DISC1 is associated with sustained attention deficits.
Key Words
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Article info
Publication history
Accepted:
April 25,
2006
Received in revised form:
April 21,
2006
Received:
November 30,
2005
Identification
Copyright
© 2006 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.
