A single nucleotide polymorphism fine mapping study of chromosome 1q42.1 reveals the vulnerability genes for schizophrenia, GNPAT and DISC1: Association with impairment of sustained attention.

Abstract:

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.

journal_name

Biol Psychiatry

journal_title

Biological psychiatry

authors

Liu YL,Fann CS,Liu CM,Chen WJ,Wu JY,Hung SI,Chen CH,Jou YS,Liu SK,Hwang TJ,Hsieh MH,Ouyang WC,Chan HY,Chen JJ,Yang WC,Lin CY,Lee SF,Hwu HG

doi

10.1016/j.biopsych.2006.04.024

subject

Has Abstract

pub_date

2006-09-15 00:00:00

pages

554-62

issue

6

eissn

0006-3223

issn

1873-2402

pii

S0006-3223(06)00535-X

journal_volume

60

pub_type

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