Show simple item record

dc.contributor.authorSherva, Richarden_US
dc.contributor.authorSripichai, Orapanen_US
dc.contributor.authorAbel, Kennethen_US
dc.contributor.authorMa, Qianlien_US
dc.contributor.authorWhitacre, Johannaen_US
dc.contributor.authorAngkachatchai, Vachen_US
dc.contributor.authorMakarasara, Wattananen_US
dc.contributor.authorWinichagoon, Praneeen_US
dc.contributor.authorSvasti, Saovarosen_US
dc.contributor.authorFucharoen, Suthaten_US
dc.contributor.authorBraun, Andreasen_US
dc.contributor.authorFarrer, Lindsay A.en_US
dc.date.accessioned2011-12-29T21:02:15Z
dc.date.available2011-12-29T21:02:15Z
dc.date.copyright2010
dc.date.issued2010-3-30
dc.identifier.citationSherva, Richard, Orapan Sripichai, Kenneth Abel, Qianli Ma, Johanna Whitacre, Vach Angkachatchai, Wattanan Makarasara, Pranee Winichagoon, Saovaros Svasti, Suthat Fucharoen, Andreas Braun, Lindsay A Farrer. "Genetic modifiers of Hb E/β0 thalassemia identified by a two-stage genome-wide association study" BMC Medical Genetics 11:51. (2010)
dc.identifier.issn1471-2350
dc.identifier.urihttps://hdl.handle.net/2144/2497
dc.description.abstractBACKGROUND: Patients with Hb E/β0 thalassemia display remarkable variability in disease severity. To identify genetic modifiers influencing disease severity, we conducted a two-stage genome scan in groups of 207 mild and 305 severe unrelated patients from Thailand with Hb E/β0 thalassemia and normal α-globin genes. METHODS: First, we estimated and compared the allele frequencies of approximately 110,000 gene-based single nucleotide polymorphisms (SNPs) in pooled DNAs from different severity groups. The 756 SNPs that showed reproducible allelic differences at P < 0.02 by pooling were selected for individual genotyping. RESULTS: After adjustment for age, gender and geographic region, logistic regression models showed 50 SNPs significantly associated with disease severity (P < 0.05) after Bonferroni adjustment for multiple testing. Forty-one SNPs in a large LD block within the β-globin gene cluster had major alleles associated with severe disease. The most significant was bthal_bg200 (odds ratio (OR) = 5.56, P = 2.6 × 10-13). Seven SNPs in two distinct LD blocks within a region centromeric to the β-globin gene cluster that contains many olfactory receptor genes were also associated with disease severity; rs3886223 had the strongest association (OR = 3.03, P = 3.7 × 10-11). Several previously unreported SNPs were also significantly associated with disease severity. CONCLUSIONS: These results suggest that there may be an additional regulatory region centromeric to the β-globin gene cluster that affects disease severity by modulating fetal hemoglobin expression.en_US
dc.description.sponsorshipNational Institutes of Health (R01-DK61883-01); Royal Golden Jubilee Scholarship from the Thailand Research Fund and National Center for Genetic Engineering and Biotechnology, Thailanden_US
dc.language.isoen
dc.publisherBioMed Centralen_US
dc.rightsCopyright 2010 Sherva et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.en_US
dc.rights.urihttp://creativecommons.org/licenses/by/2.0
dc.titleGenetic mModifiers of Hb E/β0 Thalassemia Identified by a Two-Stage Genome-Wide Association Studyen_US
dc.typeArticleen_US
dc.identifier.doi10.1186/1471-2350-11-51
dc.identifier.pmid20353593
dc.identifier.pmcid2853425


This item appears in the following Collection(s)

Show simple item record

Copyright 2010 Sherva et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Except where otherwise noted, this item's license is described as Copyright 2010 Sherva et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.