RASD2, MYH9, and CACNG2 genes at chromosome 22q12 associated with the subgroup of schizophrenia with non-deficit in sustained attention and executive function.
BACKGROUND
In a previous linkage study of schizophrenia that included Taiwanese samples, the marker D22S278 (22q12.3) was significantly linked to schizophrenia (p = .001).


METHODS
We conducted fine mapping of the implicated genomic region, with 47 validated single nucleotide polymorphism (SNP) markers around 1 Mb of D22S278, in a Taiwanese sample of 218 pedigrees with at least 2 siblings affected with schizophrenia. We examined the association of these SNPs and their haplotypes with schizophrenia and with subgroups defined by the presence and absence of deficits in sustained attention as assessed by undegraded and degraded continuous performance tests (CPTs). We also examined subgroups defined by deficits in categories achieved in the Wisconsin Card Sort Test (WCST).


RESULTS
Three of five candidate vulnerability genes (RASD2, APOL5, MYH9, EIF3S7, and CACNG2), which had marginally significant associations with schizophrenia, had significant associations with schizophrenic patients who did not have deficits in sustained attention on the undegraded CPT (RASD2 gene SNP rs736212; p = .0008 with single locus analysis) and the degraded CPT (MYH9 gene haplotype 1-1-1-1 of SNP rs3752463 - rs1557540 - rs713839 - rs739097; p = .0059 with haplotype analysis). We also found a significant association for patients who showed no deficits in executive function as measured by categories achieved in the WCST (CACNG2 gene haplotype 2-1-1-1 of SNP rs2267360 - rs140526 - rs1883987 - rs916269; p = .0163 with haplotype analysis).


CONCLUSIONS
The genes RASD2, MYH9, and CACNG2 might be vulnerability genes for neuropsychologically defined subgroups of schizophrenic patients.
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
Shi-Kai
SK
Hwang
Tzung-Jeng
TJ
Hsieh
Ming H
MH
Chang
Chien Ching
CC
Yang
Wei-Chih
WC
Lin
Jin-Jia
JJ
Chou
Frank Huang-Chih
FH
Faraone
Stephen V
SV
Tsuang
Ming T
MT
Hwu
Hai-Gwo
HG
D000328:Adult; D000368:Aged; D001288:Attention / Q000502:physiology; D015220:Calcium Channels / Q000235:genetics*; D002892:Chromosomes, Human, Pair 22; D005192:Family Health; D005260:Female; D019204:GTP-Binding Proteins / Q000235:genetics*; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D008875:Middle Aged; D020409:Molecular Motor Proteins / Q000235:genetics*; D018995:Myosin Heavy Chains / Q000235:genetics*; D009483:Neuropsychological Tests; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D011340:Problem Solving / Q000502:physiology; D012559:Schizophrenia / Q000145:classification / Q000235:genetics* / Q000503:physiopathology*
C491912:CACNG2 protein, human; D015220:Calcium Channels; C103814:MYH9 protein, human; D020409:Molecular Motor Proteins; D019204:GTP-Binding Proteins; C486702:RASD2 protein, human; D018995:Myosin Heavy Chains