biostudies-literatureMcClure AVersus ArthritisNational Institute for Health Research (NIHR)Wellcome Trust1369-74https://www.ebi.ac.uk/biostudies/studies/S-EPMC2762544biostudies-literatureUnknown48(11)<h4>Objective</h4>Five loci-the shared epitope (SE) of HLA--DRB1, the PTPN22 gene, a locus on 6q23, the STAT4 gene and a locus mapping to the TRAF1/C5 genetic region--have now been unequivocally confirmed as conferring susceptibility to RA. The largest single effect is conferred by SE. We hypothesized that combinations of susceptibility alleles may increase risk over and above that of any individual locus alone.<h4>Methods</h4>We analysed data from 4238 RA cases and 1811 controls, for which genotypes were available at all five loci.<h4>Results</h4>Statistical analysis identified eight high-risk combinations conferring an odds ratio >6 compared with carriage of no susceptibility variants and, interestingly, 10% population controls carried a combination conferring high risk. All high-risk coRheumatology (Oxford, England)Investigating the viability of genetic screening/testing for RA susceptibility using combinations of five confirmed risk loci.PMC27625441755218475NF-SI-0508-1029917 552Bowes JHocking LJEmery PDouglas KGaffney KScott DGDelamere JKlocke RCooper RCapell HHassell AKe XGordon MMWorthington JDawson JKGibbons LPace AGupta MDawes PTWordsworth PPackham JHunter JSturrock RBernstein RMThompson PWErb NLynch MHay EMSummers GDBadcock LJMarinou IWhallett AReid DMDowson CRichards SCLedingham JMMacgregor AJWilliams RAShadforth MFHull RGHarrison PRegan MRSymmons DLunt MBarton AMccrae FSnaithShaban MRMin SYDeighton CMO'Neil TJones AKnight SMadhok RHinks AMarshall TAbernethy VEThomson WHyrich KBruce INBIRAC consortiumCarpenter EHWilson AGMerry PField MEyre SPlant DMcInnes IBenitha RThomas ALSilman AHerrick AKitas GDSteer SKamath SMcClure AMorgan AWRoddy EO'Reilly SCPorter DfalseInvestigating the viability of genetic screening/testing for RA susceptibility using combinations of five confirmed risk loci.<h4>Objective</h4>Five loci-the shared epitope (SE) of HLA--DRB1, the PTPN22 gene, a locus on 6q23, the STAT4 gene and a locus mapping to the TRAF1/C5 genetic region--have now been unequivocally confirmed as conferring susceptibility to RA. The largest single effect is conferred by SE. We hypothesized that combinations of susceptibility alleles may increase risk over and above that of any individual locus alone.<h4>Methods</h4>We analysed data from 4238 RA cases and 1811 controls, for which genotypes were available at all five loci.<h4>Results</h4>Statistical analysis identified eight high-risk combinations conferring an odds ratio >6 compared with carriage of no susceptibility variants and, interestingly, 10% population controls carried a combination conferring high risk. All high-risk co2009-01-01T00:00:00Z2009 Nov2026-05-05T04:53:07.696Z2019-03-27T00:25:55ZS-EPMC27625441974100810.1093/rheumatology/kep272