Association study in the 5q31-32 linkage region for schizophrenia using pooled DNA genotyping.
BACKGROUND
Several linkage studies suggest that chromosome 5q31-32 might contain risk loci for schizophrenia (SZ). We wanted to identify susceptibility genes for schizophrenia within this region.


METHODS
We saturated the interval between markers D5S666 and D5S436 with 90 polymorphic microsatellite markers and genotyped two sets of DNA pools consisting of 300 SZ patients of Bulgarian origin and their 600 parents. Positive associations were followed-up with SNP genotyping.


RESULTS
Nominally significant evidence for association (p < 0.05) was found for seven markers (D5S0023i, IL9, RH60252, 5Q3133_33, D5S2017, D5S1481, D5S0711i) which were then individually genotyped in the trios. The predicted associations were confirmed for two of the markers: D5S2017, localised in the SPRY4-FGF1 locus (p = 0.004) and IL9, localized within the IL9 gene (p = 0.014). Fine mapping was performed using single nucleotide polymorphisms (SNPs) around D5S2017 and IL9. In each region four SNPs were chosen and individually genotyped in our full sample of 615 SZ trios. Two SNPs showed significant evidence for association: rs7715300 (p = 0.001) and rs6897690 (p = 0.032). Rs7715300 is localised between the TGFBI and SMAD5 genes and rs6897690 is within the SPRY4 gene.


CONCLUSIONS
Our screening of 5q31-32 implicates three potential candidate genes for SZ: SMAD5, TGFBI and SPRY4.
Zaharieva
Irina
I
Department of Psychological Medicine, School of Medicine, Cardiff University, Heath Park, Cardiff CF14 4XN, UK. irinazaharieva@yahoo.co.uk
Georgieva
Lyudmila
L
Nikolov
Ivan
I
Kirov
George
G
Owen
Michael J
MJ
O'Donovan
Michael C
MC
Toncheva
Draga
D
D000328:Adult; D002648:Child; D002895:Chromosomes, Human, Pair 5 / Q000235:genetics*; D016326:Extracellular Matrix Proteins / Q000235:genetics; D016220:Fibroblast Growth Factor 1 / Q000235:genetics; D005788:Gene Pool; D008040:Genetic Linkage; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics; D018895:Microsatellite Repeats / Q000235:genetics; D009419:Nerve Tissue Proteins / Q000235:genetics; D017354:Point Mutation / Q000235:genetics; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D015995:Prevalence; D012559:Schizophrenia / Q000453:epidemiology / Q000235:genetics*; D051902:Smad5 Protein / Q000235:genetics; D016212:Transforming Growth Factor beta / Q000235:genetics; D000099222:betaIG-H3 Protein
D016326:Extracellular Matrix Proteins; D016220:Fibroblast Growth Factor 1; D047908:Intracellular Signaling Peptides and Proteins; D009419:Nerve Tissue Proteins; D051902:Smad5 Protein; D016212:Transforming Growth Factor beta; D000099222:betaIG-H3 Protein; C497797:SMAD5 protein, human; C499038:SPRY4 protein, human