Transmission disequilibrium and haplotype analyses of the G72/G30 locus: suggestive linkage to schizophrenia in Palestinian Arabs living in the North of Israel.
Association of the G72/G30 locus with schizophrenia was recently reported in French Canadian, Russian, and Ashkenazi populations using case-control studies. In the present study we hypothesize the existence of a G72/G30 risk allele over-transmitted to affected sibs in Palestinian Arab families. A total of 223 Palestinian Arab families that included an affected offspring and parents were genotyped with 11 SNPs encompassing the G72/G30 genes. The families were recruited from three regions of Israel: 56 from the North (Afula), 136 from the central hill region (Bethlehem, Palestinian Authority), and 31 from the South (Beersheva). Individual SNP analyses disclosed a risk allele in SNP rs3916970 by both haplotype relative risk (HRR: chi(2) = 5.59, P = 0.018) and transmission disequilibrium test (TDT: chi(2) = 6.03, P = 0.014) in the Afula families. Follow-up multilocus analysis using family-based association tests (FBAT: z = 2.197, P = 0.028) exposed the adjacent haplotype. SNP rs3916970 is located about 8 kb from the linkage disequilibrium block that was reported to be associated with schizophrenia in Ashkenazi Jews. Excess of similar haplotypes of this region was observed in the Palestinian Arabs and the Ashkenazi patients. These data suggest a common risk factor for schizophrenia susceptibility in the G72/G30 locus among Ashkenazi Jews and Palestinian Arabs. The results strengthen previous reports on the role of this locus in the etiology of schizophrenia.
Korostishevsky
M
M
Department of Human Genetics and Molecular Medicine, Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel 69978.
Kremer
I
I
Kaganovich
M
M
Cholostoy
A
A
Murad
I
I
Muhaheed
M
M
Bannoura
I
I
Rietschel
M
M
Dobrusin
M
M
Bening-Abu-Shach
U
U
Belmaker
R H
RH
Maier
W
W
Ebstein
R P
RP
Navon
Ruth
R
D000483:Alleles; D018912:Arabs / Q000208:ethnology / Q000235:genetics; D002352:Carrier Proteins / Q000235:genetics*; D005192:Family Health; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006239:Haplotypes / Q000235:genetics*; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D007557:Israel; D015810:Linkage Disequilibrium; D008297:Male; D009679:Nuclear Family; D020641:Polymorphism, Single Nucleotide; D011506:Proteins / Q000235:genetics*; D012333:RNA, Messenger; D012559:Schizophrenia / Q000235:genetics*
D002352:Carrier Proteins; C475071:DAOA protein, human; C488199:DAOAAS gene product, human; D047908:Intracellular Signaling Peptides and Proteins; D011506:Proteins; D012333:RNA, Messenger