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Evidence for gene–gene epistatic interactions among susceptibility loci for systemic lupus erythematosus

dc.contributor.authorHughes, Travisen_US
dc.contributor.authorAdler, Adamen_US
dc.contributor.authorKelly, Jennifer A.en_US
dc.contributor.authorKaufman, Kenneth M.en_US
dc.contributor.authorWilliams, Adrienne H.en_US
dc.contributor.authorLangefeld, Carl D.en_US
dc.contributor.authorBrown, Elizabeth E.en_US
dc.contributor.authorAlarcón, Graciela S.en_US
dc.contributor.authorKimberly, Robert P.en_US
dc.contributor.authorEdberg, Jeffrey C.en_US
dc.contributor.authorRamsey‐goldman, Rosalinden_US
dc.contributor.authorPetri, Michelle A.en_US
dc.contributor.authorBoackle, Susan A.en_US
dc.contributor.authorStevens, Anne M.en_US
dc.contributor.authorReveille, John D.en_US
dc.contributor.authorSanchez, Elenaen_US
dc.contributor.authorMartín, Javieren_US
dc.contributor.authorNiewold, Timothy B.en_US
dc.contributor.authorVilá, Luis M.en_US
dc.contributor.authorScofield, R. Halen_US
dc.contributor.authorGilkeson, Gary S.en_US
dc.contributor.authorGaffney, Patrick M.en_US
dc.contributor.authorCriswell, Lindsey A.en_US
dc.contributor.authorMoser, Kathy L.en_US
dc.contributor.authorMerrill, Joan T.en_US
dc.contributor.authorJacob, Chaim O.en_US
dc.contributor.authorTsao, Betty P.en_US
dc.contributor.authorJames, Judith A.en_US
dc.contributor.authorVyse, Timothy J.en_US
dc.contributor.authorAlarcón‐riquelme, Marta E.en_US
dc.contributor.authorHarley, John B.en_US
dc.contributor.authorRichardson, Bruce C.en_US
dc.contributor.authorSawalha, Amr H.en_US
dc.date.accessioned2012-03-16T16:00:38Z
dc.date.available2013-04-01T14:17:24Zen_US
dc.date.issued2012-02en_US
dc.identifier.citationHughes, Travis; Adler, Adam; Kelly, Jennifer A.; Kaufman, Kenneth M.; Williams, Adrienne H.; Langefeld, Carl D.; Brown, Elizabeth E.; Alarcón, Graciela S. ; Kimberly, Robert P.; Edberg, Jeffrey C.; Ramsey‐goldman, Rosalind ; Petri, Michelle; Boackle, Susan A.; Stevens, Anne M.; Reveille, John D.; Sanchez, Elena; Martín, Javier ; Niewold, Timothy B.; Vilá, Luis M. ; Scofield, R. Hal; Gilkeson, Gary S.; Gaffney, Patrick M.; Criswell, Lindsey A.; Moser, Kathy L.; Merrill, Joan T.; Jacob, Chaim O.; Tsao, Betty P.; James, Judith A.; Vyse, Timothy J.; Alarcón‐riquelme, Marta E. ; Harley, John B.; Richardson, Bruce C.; Sawalha, Amr H. (2012). "Evidence for geneâ gene epistatic interactions among susceptibility loci for systemic lupus erythematosus." Arthritis & Rheumatism 64(2): 485-492. <http://hdl.handle.net/2027.42/90353>en_US
dc.identifier.issn0004-3591en_US
dc.identifier.issn1529-0131en_US
dc.identifier.urihttps://hdl.handle.net/2027.42/90353
dc.description.abstractObjective Several confirmed genetic susceptibility loci for lupus have been described. To date, no clear evidence for genetic epistasis in lupus has been established. The aim of this study was to test for gene–gene interactions in a number of known lupus susceptibility loci. Methods Eighteen single‐nucleotide polymorphisms tagging independent and confirmed lupus susceptibility loci were genotyped in a set of 4,248 patients with lupus and 3,818 normal healthy control subjects of European descent. Epistasis was tested by a 2‐step approach using both parametric and nonparametric methods. The false discovery rate (FDR) method was used to correct for multiple testing. Results We detected and confirmed gene–gene interactions between the HLA region and CTLA4 , IRF5 , and ITGAM and between PDCD1 and IL21 in patients with lupus. The most significant interaction detected by parametric analysis was between rs3131379 in the HLA region and rs231775 in CTLA4 (interaction odds ratio 1.19, Z = 3.95, P = 7.8 × 10 −5 [FDR ≤0.05], P for multifactor dimensionality reduction = 5.9 × 10 −45 ). Importantly, our data suggest that in patients with lupus, the presence of the HLA lupus risk alleles in rs1270942 and rs3131379 increases the odds of also carrying the lupus risk allele in IRF5 (rs2070197) by 17% and 16%, respectively ( P = 0.0028 and P = 0.0047, respectively). Conclusion We provide evidence for gene–gene epistasis in systemic lupus erythematosus. These findings support a role for genetic interaction contributing to the complexity of lupus heritability.en_US
dc.publisherWiley Subscription Services, Inc., A Wiley Companyen_US
dc.titleEvidence for gene–gene epistatic interactions among susceptibility loci for systemic lupus erythematosusen_US
dc.typeArticleen_US
dc.rights.robotsIndexNoFollowen_US
dc.subject.hlbsecondlevelGeriatricsen_US
dc.subject.hlbtoplevelHealth Sciencesen_US
dc.description.peerreviewedPeer Revieweden_US
dc.contributor.affiliationumUniversity of Michigan and Ann Arbor VA Medical Center, Ann Arboren_US
dc.contributor.affiliationotherUniversity of Puerto Rico, San Juan, Puerto Ricoen_US
dc.contributor.affiliationotherOklahoma Medical Research Foundation, Oklahoma Cityen_US
dc.contributor.affiliationotherOklahoma Medical Research Foundation, University of Oklahoma Health Sciences Center, and Oklahoma City VA Medical Center, Oklahoma Cityen_US
dc.contributor.affiliationotherWake Forest University Health Sciences Center, Winston‐Salem, North Carolinaen_US
dc.contributor.affiliationotherUniversity of Alabama at Birminghamen_US
dc.contributor.affiliationotherNorthwestern University Feinberg School of Medicine, Chicago, Illinoisen_US
dc.contributor.affiliationotherJohns Hopkins University School of Medicine, Baltimore, Marylanden_US
dc.contributor.affiliationotherUniversity of Colorado Denver School of Medicine, Auroraen_US
dc.contributor.affiliationotherUniversity of Washington and Seattle Children's Research Institute, Seattleen_US
dc.contributor.affiliationotherUniversity of Texas Health Science Center at Houstonen_US
dc.contributor.affiliationotherInstituto de Parasitología y Biomedicina López‐Neyra, CSIC, Granada, Spainen_US
dc.contributor.affiliationotherUniversity of Chicago, Chicago, Illinoisen_US
dc.contributor.affiliationotherMedical University of South Carolina, Charlestonen_US
dc.contributor.affiliationotherUniversity of California, San Franciscoen_US
dc.contributor.affiliationotherOklahoma Medical Research Foundation and University of Oklahoma Health Sciences Center, Oklahoma Cityen_US
dc.contributor.affiliationotherUniversity of Southern California, Los Angelesen_US
dc.contributor.affiliationotherUniversity of California, Los Angelesen_US
dc.contributor.affiliationotherKing's College London and Guy's Hospital, London, UKen_US
dc.contributor.affiliationotherOklahoma Medical Research Foundation, Oklahoma Cityen_US
dc.contributor.affiliationotherCincinnati Children's Hospital Medical Center and Cincinnati VA Medical Center, Cincinnati, Ohioen_US
dc.contributor.affiliationotherCenter for Genomics and Oncological Research Pfizer–University of Granada–Junta de Andalucia, Granada, Spainen_US
dc.contributor.affiliationotherOklahoma Medical Research Foundation, 825 Northeast 13th Street, MS#24, Oklahoma City, OK 73104en_US
dc.identifier.pmid21952918en_US
dc.description.bitstreamurlhttp://deepblue.lib.umich.edu/bitstream/2027.42/90353/1/33354_ftp.pdf
dc.identifier.doi10.1002/art.33354en_US
dc.identifier.sourceArthritis & Rheumatismen_US
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dc.owningcollnameInterdisciplinary and Peer-Reviewed


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