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BMC Psychiatry
Published in: BMC Psychiatry 1/2008

Open Access 01-12-2008 | Research article

Association study in the 5q31-32 linkage region for schizophrenia using pooled DNA genotyping

Authors: Irina Zaharieva, Lyudmila Georgieva, Ivan Nikolov, George Kirov, Michael J Owen, Michael C O'Donovan, Draga Toncheva

Published in: BMC Psychiatry | Issue 1/2008

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Abstract

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.

Conclusion

Our screening of 5q31-32 implicates three potential candidate genes for SZ: SMAD5, TGFBI and SPRY4.
Appendix
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Metadata
Title
Association study in the 5q31-32 linkage region for schizophrenia using pooled DNA genotyping
Authors
Irina Zaharieva
Lyudmila Georgieva
Ivan Nikolov
George Kirov
Michael J Owen
Michael C O'Donovan
Draga Toncheva
Publication date
01-12-2008
Publisher
BioMed Central
Published in
BMC Psychiatry / Issue 1/2008
Electronic ISSN: 1471-244X
DOI
https://doi.org/10.1186/1471-244X-8-11

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