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

Zaharieva I, Georgieva L, Nikolov I, Kirov G, Owen MJ, O'Donovan MC, Toncheva D - BMC Psychiatry (2008)

Bottom Line: 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.Two SNPs showed significant evidence for association: rs7715300 (p = 0.001) and rs6897690 (p = 0.032).Our screening of 5q31-32 implicates three potential candidate genes for SZ: SMAD5, TGFBI and SPRY4.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Psychological Medicine, School of Medicine, Cardiff University, Heath Park, Cardiff CF14 4XN, UK. irinazaharieva@yahoo.co.uk

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.

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Related in: MedlinePlus

Markers and genes in the region around D5S2017 marker. Included are base pair position according to UCSC built 35, May 2004, chromosome band, gene and the genotyped SNPs and microsatellite markers within the region.
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Figure 3: Markers and genes in the region around D5S2017 marker. Included are base pair position according to UCSC built 35, May 2004, chromosome band, gene and the genotyped SNPs and microsatellite markers within the region.

Mentions: In order to further investigate the two candidate regions, we performed fine mapping using SNPs. Eight SNPs were selected from regions of 400 kb surrounding the microsatellites D5S2017 and IL9 from the data of our GWA study in 574 SZ trios carried out in the same population (see Methods). These eight SNPs had shown suggestive significance for association (p = 0.05) in the pooling data. Rs17169180, rs1859430, rs30747 and rs7715300 are around the IL9 area, and rs2961720, rs7443175, rs6897690 and rs153423 are from the D5S2017 area (Figures 2 and 3). We could not produce a robust assay for genotyping rs2961720, so we substituted it with rs2906066 which was in complete LD with rs2961720 (r2 = 1) in the CEU trios sample (Utah residents with ancestry from Northern and Western Europe) from HapMap [41]. Results from the individual genotyping are presented in Table 2.


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

Zaharieva I, Georgieva L, Nikolov I, Kirov G, Owen MJ, O'Donovan MC, Toncheva D - BMC Psychiatry (2008)

Markers and genes in the region around D5S2017 marker. Included are base pair position according to UCSC built 35, May 2004, chromosome band, gene and the genotyped SNPs and microsatellite markers within the region.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2268687&req=5

Figure 3: Markers and genes in the region around D5S2017 marker. Included are base pair position according to UCSC built 35, May 2004, chromosome band, gene and the genotyped SNPs and microsatellite markers within the region.
Mentions: In order to further investigate the two candidate regions, we performed fine mapping using SNPs. Eight SNPs were selected from regions of 400 kb surrounding the microsatellites D5S2017 and IL9 from the data of our GWA study in 574 SZ trios carried out in the same population (see Methods). These eight SNPs had shown suggestive significance for association (p = 0.05) in the pooling data. Rs17169180, rs1859430, rs30747 and rs7715300 are around the IL9 area, and rs2961720, rs7443175, rs6897690 and rs153423 are from the D5S2017 area (Figures 2 and 3). We could not produce a robust assay for genotyping rs2961720, so we substituted it with rs2906066 which was in complete LD with rs2961720 (r2 = 1) in the CEU trios sample (Utah residents with ancestry from Northern and Western Europe) from HapMap [41]. Results from the individual genotyping are presented in Table 2.

Bottom Line: 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.Two SNPs showed significant evidence for association: rs7715300 (p = 0.001) and rs6897690 (p = 0.032).Our screening of 5q31-32 implicates three potential candidate genes for SZ: SMAD5, TGFBI and SPRY4.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Psychological Medicine, School of Medicine, Cardiff University, Heath Park, Cardiff CF14 4XN, UK. irinazaharieva@yahoo.co.uk

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.

Show MeSH
Related in: MedlinePlus