title: Increased risk of rheumatoid arthritis among mothers with children who carryDRB1risk-associated alleles.
abstract: OBJECTIVE
  To investigate whether a child's genotype affects a mother's risk of rheumatoid arthritis (RA) beyond the risk associated with her genotype and to test whether exposure to fetal alleles inherited from the father increases risk of RA among mothers without risk alleles.
  
  
  METHODS
  A case-control study was conducted among 1165 mothers (170 cases/995 controls) and their respective 1482 children. We tested the association between having any child with alleles encoding amino acids (AAs) associated with RA including the 'shared epitope' (SE) and DERAA AA sequences at positions 70-74; AA valine, lysine and alanine at positions 11, 71 and 74 of HLA-DRB1; aspartic acid at position 9 of HLA-B and phenylalanine at position 9 of DPB1. We used logistic regression models to estimate OR and 95% CI for each group of alleles, adjusting for maternal genotype and number of live births.
  
  
  RESULTS
  We found increased risk of RA among mothers who had any child with SE (OR 3.0; 95% CI 2.0 to 4.6); DERAA (OR 1.7; 95% CI 1.1 to 2.6); or valine (OR 2.3; 95% CI 1.6 to 3.5), lysine (OR 2.3; 95% CI 1.5 to 3.4) and alanine (OR 2.8; 95% CI 1.2 to 6.4) at DRB1 positions 11, 71 and 74, respectively. Among non-carrier mothers, increased risk of RA was associated with having children who carried DERAA (OR 1.7; 95% CI 1.0 to 2.7) and alleles encoding lysine at DRB1 position 71 (OR 2.3; 95% CI 1.5 to 4.8).
  
  
  CONCLUSIONS
  Findings support the hypothesis that a child's genotype can contribute independently to risk of RA among mothers.
authors.affiliation: School of Public Health, University of California Berkeley, Berkeley, California, USA.
authors.forename: Giovanna Ibeth
authors.initials: GI
authors.lastname: Cruz
authors.affiliation: School of Public Health, University of California Berkeley, Berkeley, California, USA.
authors.forename: Xiaorong
authors.initials: X
authors.lastname: Shao
authors.affiliation: School of Public Health, University of California Berkeley, Berkeley, California, USA.
authors.forename: Hong
authors.initials: H
authors.lastname: Quach
authors.affiliation: Department of Medicine, University of San Francisco, Rosalind Russell/Ephraim P. Engleman Rheumatology Research Center, San Francisco, California, USA.
authors.forename: Kimberly A
authors.initials: KA
authors.lastname: Ho
authors.affiliation: Department of Medicine, University of San Francisco, Rosalind Russell/Ephraim P. Engleman Rheumatology Research Center, San Francisco, California, USA.
authors.forename: Kirsten
authors.initials: K
authors.lastname: Sterba
authors.affiliation: Childrens Hospital Oakland Research Institute, Oakland, California, USA.
authors.forename: Janelle A
authors.initials: JA
authors.lastname: Noble
authors.affiliation: Broad Institute of Harvard and Massachusetts Institute of Technology, Cambridge, USA.
authors.forename: Nikolaos A
authors.initials: NA
authors.lastname: Patsopoulos
authors.affiliation: Laboratory of Medicine, Blood Systems Research Institute, San Francisco, California, USA.
authors.forename: Michael P
authors.initials: MP
authors.lastname: Busch
authors.affiliation: Department of Pathology, University of Pittsburgh, Institute for Transfusion Medicine, Pittsburgh, Pennsylvania, USA.
authors.forename: Darrell J
authors.initials: DJ
authors.lastname: Triulzi
authors.affiliation: Division of Medical Genomics, Inova Translational Medicine Institute, Falls Church, Virginia, USA.
authors.forename: Wendy Sw
authors.initials: WS
authors.lastname: Wong
authors.affiliation: Division of Medical Genomics, Inova Translational Medicine Institute, Falls Church, Virginia, USA.
authors.forename: Benjamin D
authors.initials: BD
authors.lastname: Solomon
authors.affiliation: Division of Medical Genomics, Inova Translational Medicine Institute, Falls Church, Virginia, USA.
authors.forename: John E
authors.initials: JE
authors.lastname: Niederhuber
authors.affiliation: Department of Medicine, University of California, San Francisco, San Francisco, California, USA.
authors.forename: Lindsey A
authors.initials: LA
authors.lastname: Criswell
authors.affiliation: Division of Epidemiology, School of Public Health, University of California Berkeley, Berkeley, California, USA.
authors.forename: Lisa F
authors.initials: LF
authors.lastname: Barcellos
mesh_terms: D000328:Adult; D000368:Aged; D000483:Alleles; D001172:Arthritis, Rheumatoid / Q000453:epidemiology* / Q000235:genetics; D016022:Case-Control Studies; D005260:Female; D005838:Genotype; D015235:HLA-B Antigens / Q000235:genetics*; D059868:HLA-DP beta-Chains / Q000235:genetics*; D059811:HLA-DRB1 Chains / Q000235:genetics*; D006801:Humans; D016015:Logistic Models; D018811:Maternal Exposure / Q000706:statistics & numerical data*; D008875:Middle Aged; D009035:Mothers / Q000706:statistics & numerical data*; D015999:Multivariate Analysis; D016017:Odds Ratio
chemical_list: D015235:HLA-B Antigens; D059868:HLA-DP beta-Chains; C071170:HLA-DPB1 antigen; D059811:HLA-DRB1 Chains
keywords: Rheumatoid arthritis; autoimmune disease; epidemiology