OBJECTIVE: We assessed the contributions of familial rheumatoid arthritis (RA) or lupus and environmental factors to the risk of RA. METHODS: Among 121,700 women in the Nurses' Health Study, 65,457 provided data on familial RA/lupus. Among these, 493 RA cases (301 seropositive and 192 seronegative) were validated. We estimated hazard ratios (HRs) for RA comparing those with and without familial RA/lupus, adjusting for environmental factors (smoking, alcohol, body mass index [BMI], parity, breastfeeding, menopause, hormone use, early menarche, and menstrual regularity) using Cox proportional hazards models. Population attributable risks (PARs) for RA within this cohort were calculated for familial RA/lupus, smoking, alcohol, BMI, parity, and breastfeeding. RESULTS: Familial RA/lupus was significantly associated with RA (HR 3.67), seropositive RA (HR 3.90), and seronegative RA (HR 3.95). After adjusting for environmental factors, familial RA/lupus was significantly associated with RA (HR 3.59, 95% confidence interval 2.94-4.37). Smoking >10 pack-years, overweight, BMI, and premenopause status remained significantly associated with RA after adjusting for familial RA/lupus. For RA in this cohort, the PAR for smoking, BMI, alcohol, parity, or breastfeeding collectively was 41%; the PAR due to heredity from familial RA/lupus was 21%. CONCLUSION: In this large, prospective cohort, women with familial RA/lupus had a 4-fold increased risk for RA that remained significant after adjusting for environmental factors. A large proportion of RA risk was attributable to environmental factors, even among those with familial RA/lupus.
OBJECTIVE: We assessed the contributions of familial rheumatoid arthritis (RA) or lupus and environmental factors to the risk of RA. METHODS: Among 121,700 women in the Nurses' Health Study, 65,457 provided data on familial RA/lupus. Among these, 493 RA cases (301 seropositive and 192 seronegative) were validated. We estimated hazard ratios (HRs) for RA comparing those with and without familial RA/lupus, adjusting for environmental factors (smoking, alcohol, body mass index [BMI], parity, breastfeeding, menopause, hormone use, early menarche, and menstrual regularity) using Cox proportional hazards models. Population attributable risks (PARs) for RA within this cohort were calculated for familial RA/lupus, smoking, alcohol, BMI, parity, and breastfeeding. RESULTS:Familial RA/lupus was significantly associated with RA (HR 3.67), seropositive RA (HR 3.90), and seronegative RA (HR 3.95). After adjusting for environmental factors, familial RA/lupus was significantly associated with RA (HR 3.59, 95% confidence interval 2.94-4.37). Smoking >10 pack-years, overweight, BMI, and premenopause status remained significantly associated with RA after adjusting for familial RA/lupus. For RA in this cohort, the PAR for smoking, BMI, alcohol, parity, or breastfeeding collectively was 41%; the PAR due to heredity from familial RA/lupus was 21%. CONCLUSION: In this large, prospective cohort, women with familial RA/lupus had a 4-fold increased risk for RA that remained significant after adjusting for environmental factors. A large proportion of RA risk was attributable to environmental factors, even among those with familial RA/lupus.
Authors: Eli A Stahl; Soumya Raychaudhuri; Elaine F Remmers; Gang Xie; Stephen Eyre; Brian P Thomson; Yonghong Li; Fina A S Kurreeman; Alexandra Zhernakova; Anne Hinks; Candace Guiducci; Robert Chen; Lars Alfredsson; Christopher I Amos; Kristin G Ardlie; Anne Barton; John Bowes; Elisabeth Brouwer; Noel P Burtt; Joseph J Catanese; Jonathan Coblyn; Marieke J H Coenen; Karen H Costenbader; Lindsey A Criswell; J Bart A Crusius; Jing Cui; Paul I W de Bakker; Philip L De Jager; Bo Ding; Paul Emery; Edward Flynn; Pille Harrison; Lynne J Hocking; Tom W J Huizinga; Daniel L Kastner; Xiayi Ke; Annette T Lee; Xiangdong Liu; Paul Martin; Ann W Morgan; Leonid Padyukov; Marcel D Posthumus; Timothy R D J Radstake; David M Reid; Mark Seielstad; Michael F Seldin; Nancy A Shadick; Sophia Steer; Paul P Tak; Wendy Thomson; Annette H M van der Helm-van Mil; Irene E van der Horst-Bruinsma; C Ellen van der Schoot; Piet L C M van Riel; Michael E Weinblatt; Anthony G Wilson; Gert Jan Wolbink; B Paul Wordsworth; Cisca Wijmenga; Elizabeth W Karlson; Rene E M Toes; Niek de Vries; Ann B Begovich; Jane Worthington; Katherine A Siminovitch; Peter K Gregersen; Lars Klareskog; Robert M Plenge Journal: Nat Genet Date: 2010-05-09 Impact factor: 38.330
Authors: Rodolfo Valdez; Paula W Yoon; Nadeem Qureshi; Ridgely Fisk Green; Muin J Khoury Journal: Annu Rev Public Health Date: 2010 Impact factor: 21.981
Authors: Henrik Källberg; Bo Ding; Leonid Padyukov; Camilla Bengtsson; Johan Rönnelid; Lars Klareskog; Lars Alfredsson Journal: Ann Rheum Dis Date: 2010-12-13 Impact factor: 19.103
Authors: Annmarie Wesley; Camilla Bengtsson; Ann-Charlotte Elkan; Lars Klareskog; Lars Alfredsson; Sara Wedrén Journal: Arthritis Care Res (Hoboken) Date: 2013-01 Impact factor: 4.794
Authors: Lori B Chibnik; Lisa A Mandl; Karen H Costenbader; Peter H Schur; Elizabeth W Karlson Journal: J Rheumatol Date: 2009-02-17 Impact factor: 4.666
Authors: Jeffrey A Sparks; Shun-Chiao Chang; Katherine P Liao; Bing Lu; Alexander R Fine; Daniel H Solomon; Karen H Costenbader; Elizabeth W Karlson Journal: Arthritis Care Res (Hoboken) Date: 2016-06 Impact factor: 4.794
Authors: Maria G Prado; Maura D Iversen; Zhi Yu; Rachel Miller Kroouze; Nellie A Triedman; Sarah S Kalia; Bing Lu; Robert C Green; Elizabeth W Karlson; Jeffrey A Sparks Journal: Arthritis Care Res (Hoboken) Date: 2018-10 Impact factor: 4.794
Authors: Jeffrey A Sparks; Maura D Iversen; Rachel Miller Kroouze; Taysir G Mahmoud; Nellie A Triedman; Sarah S Kalia; Michael L Atkinson; Bing Lu; Kevin D Deane; Karen H Costenbader; Robert C Green; Elizabeth W Karlson Journal: Contemp Clin Trials Date: 2014-08-20 Impact factor: 2.226
Authors: Julia A Ford; Xinyi Liu; Allison A Marshall; Alessandra Zaccardelli; Maria G Prado; Charlene Wiyarand; Bing Lu; Elizabeth W Karlson; Peter H Schur; Kevin D Deane; Jeffrey A Sparks Journal: Arthritis Care Res (Hoboken) Date: 2019-12 Impact factor: 4.794
Authors: M Kristen Demoruelle; Kylie K Harrall; Linh Ho; Monica M Purmalek; Nickie L Seto; Heather M Rothfuss; Michael H Weisman; Joshua J Solomon; Aryeh Fischer; Yuko Okamoto; Lindsay B Kelmenson; Mark C Parish; Marie Feser; Chelsie Fleischer; Courtney Anderson; Michael Mahler; Jill M Norris; Mariana J Kaplan; Brian D Cherrington; V Michael Holers; Kevin D Deane Journal: Arthritis Rheumatol Date: 2017-05-02 Impact factor: 10.995
Authors: Jeffrey A Sparks; Shun-Chiao Chang; Kevin D Deane; Ryan W Gan; M Kristen Demoruelle; Marie L Feser; LauraKay Moss; Jane H Buckner; Richard M Keating; Karen H Costenbader; Peter K Gregersen; Michael H Weisman; Ted R Mikuls; James R O'Dell; V Michael Holers; Jill M Norris; Elizabeth W Karlson Journal: Arthritis Rheumatol Date: 2016-08 Impact factor: 10.995