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.
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.
Liu
Yu-Li
YL
Division of Mental Health and Substance Abuse Research, National Health Research Institutes, Taipei, Taiwan.
Fann
Cathy Shen-Jang
CS
Liu
Chih-Min
CM
Chen
Wei J
WJ
Wu
Jer-Yuarn
JY
Hung
Shuen-Iu
SI
Chen
Chun-Houh
CH
Jou
Yuh-Shan
YS
Liu
Shih-Kai
SK
Hwang
Tzung-Jeng
TJ
Hsieh
Ming H
MH
Ouyang
Wen-Chen
WC
Chan
Hung-Yu
HY
Chen
Jiann-Jyh
JJ
Yang
Wei-Chih
WC
Lin
Chin-Yu
CY
Lee
Sandy F C
SF
Hwu
Hai-Gwo
HG
D000217:Acyltransferases / Q000235:genetics*; D001288:Attention / Q000502:physiology*; D002874:Chromosome Mapping; D002878:Chromosomes, Human, Pair 1; D005192:Family Health; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D015810:Linkage Disequilibrium; D008297:Male; D009419:Nerve Tissue Proteins / Q000235:genetics*; D009483:Neuropsychological Tests / Q000706:statistics & numerical data; D020641:Polymorphism, Single Nucleotide; D012559:Schizophrenia / Q000150:complications / Q000235:genetics* / Q000503:physiopathology
C412476:DISC1 protein, human; D009419:Nerve Tissue Proteins; D000217:Acyltransferases; C020051:glycerone-phosphate O-acyltransferase