Genetic Risk Score Predicting Risk of Rheumatoid Arthritis Phenotypes and Age of Symptom Onset 英文参考文献.docVIP
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Genetic Risk Score Predicting Risk of Rheumatoid Arthritis Phenotypes and Age of Symptom Onset 英文参考文献
GeneticRiskScorePredictingRiskofRheumatoid
ArthritisPhenotypesandAgeofSymptomOnset
LoriB.Chibnik1*,BrendanT.Keenan1,JingCui2,KatherineP.Liao2,KarenH.Costenbader2,RobertM.
Plenge3,ElizabethW.Karlson2
1Program in Translational NeuroPsychiatric Genomics, Department of Neurology, Brigham and Women’s Hospital, Boston, Massachusetts, United States of America,
2Section of Clinical Sciences, Division of Rheumatology, Immunology and Allergy, Department of Medicine, Brigham and Women’s Hospital, Boston, Massachusetts,
United States of America, 3Division of Rheumatology, Immunology and Allergy, Department of Medicine and Division of Genetics, Brigham and Women’s Hospital,
Boston,Massachusetts,UnitedStatesofAmerica
Abstract
Background: Cumulative genetic profiles can help identify individuals at high-risk for developing RA. We examined the
impactof39validatedgeneticriskallelesontheriskofRAphenotypescharacterizedbyserologicanderosivestatus.
Methods/Principal Findings: We evaluated single nucleotide polymorphisms at 31 validated RA risk loci and 8 Human
LeukocyteAntigenallelesamong542CaucasianRAcasesand551CaucasiancontrolsfromNurses’HealthStudyandNurses’
HealthStudyII.Wecreatedaweightedgeneticriskscore(GRS)andevaluateditas7ordinalgroupsusinglogisticregression
(adjustingforageandsmoking)toassesstherelationshipbetweenGRSgroupandoddsofdevelopingseronegative(RF2
andCCP2),seropositive(RF+orCCP+),erosive,andseropositive,erosiveRAphenotypes.Inseparatecaseonlyanalyses,we
assessedtherelationshipsbetweenGRSandageofsymptomonset.In542RAcases,317(58%)wereseropositive,163(30%)
haderosionsand105(19%)wereseropositivewitherosions.ComparingthehighestGRSriskgrouptothemediangroup,
wefoundanORof1.2(95%CI=0.8–2.1)forseronegativeRA,3.0(95%CI=1.9–4.7)forseropositiveRA,3.2(95%CI=1.8–5.6)
forerosiveRA,and7.6(95%CI=3.6–16.3)forseropositive,erosiveRA.NosignificantrelationshipwasseenbetweenGRS
andageofonset.
Conclusions/Significance: Results suggest that seronegative and seropositive/erosive RA have diff
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