title: Analysis of autosomal genes reveals gene-sex interactions and higher total genetic risk in men with systemic lupus erythematosus.
abstract: OBJECTIVE
  Systemic lupus erythematosus (SLE) is a sexually dimorphic autoimmune disease which is more common in women, but affected men often experience a more severe disease. The genetic basis of sexual dimorphism in SLE is not clearly defined. A study was undertaken to examine sex-specific genetic effects among SLE susceptibility loci.
  
  
  METHODS
  A total of 18 autosomal genetic susceptibility loci for SLE were genotyped in a large set of patients with SLE and controls of European descent, consisting of 5932 female and 1495 male samples. Sex-specific genetic association analyses were performed. The sex-gene interaction was further validated using parametric and non-parametric methods. Aggregate differences in sex-specific genetic risk were examined by calculating a cumulative genetic risk score for SLE in each individual and comparing the average genetic risk between male and female patients.
  
  
  RESULTS
  A significantly higher cumulative genetic risk for SLE was observed in men than in women. (P=4.52x10-8) A significant sex-gene interaction was seen primarily in the human leucocyte antigen (HLA) region but also in IRF5, whereby men with SLE possess a significantly higher frequency of risk alleles than women. The genetic effect observed in KIAA1542 is specific to women with SLE and does not seem to have a role in men.
  
  
  CONCLUSIONS
  The data indicate that men require a higher cumulative genetic load than women to develop SLE. These observations suggest that sex bias in autoimmunity could be influenced by autosomal genetic susceptibility loci.
authors: Arthritis and Clinical Immunology Program, Oklahoma Medical Research Foundation, Oklahoma City, Oklahoma, USA.
authors: Travis
authors: T
authors: Hughes
authors: Adam
authors: A
authors: Adler
authors: Joan T
authors: JT
authors: Merrill
authors: Jennifer A
authors: JA
authors: Kelly
authors: Kenneth M
authors: KM
authors: Kaufman
authors: Adrienne
authors: A
authors: Williams
authors: Carl D
authors: CD
authors: Langefeld
authors: Gary S
authors: GS
authors: Gilkeson
authors: Elena
authors: E
authors: Sanchez
authors: Javier
authors: J
authors: Martin
authors: Susan A
authors: SA
authors: Boackle
authors: Anne M
authors: AM
authors: Stevens
authors: Graciela S
authors: GS
authors: Alarcón
authors: Timothy B
authors: TB
authors: Niewold
authors: Elizabeth E
authors: EE
authors: Brown
authors: Robert P
authors: RP
authors: Kimberly
authors: Jeffrey C
authors: JC
authors: Edberg
authors: Rosalind
authors: R
authors: Ramsey-Goldman
authors: Michelle
authors: M
authors: Petri
authors: John D
authors: JD
authors: Reveille
authors: Lindsey A
authors: LA
authors: Criswell
authors: Luis M
authors: LM
authors: Vilá
authors: Chaim O
authors: CO
authors: Jacob
authors: Patrick M
authors: PM
authors: Gaffney
authors: Kathy L
authors: KL
authors: Moser
authors: Timothy J
authors: TJ
authors: Vyse
authors: Marta E
authors: ME
authors: Alarcón-Riquelme
authors: Judith A
authors: JA
authors: James
authors: Betty P
authors: BP
authors: Tsao
authors: R Hal
authors: RH
authors: Scofield
authors: John B
authors: JB
authors: Harley
authors: Bruce C
authors: BC
authors: Richardson
authors: Amr H
authors: AH
authors: Sawalha
mesh_terms: D016022:Case-Control Studies; D005260:Female; D008040:Genetic Linkage; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008180:Lupus Erythematosus, Systemic / Q000235:genetics*; D008297:Male; D020641:Polymorphism, Single Nucleotide; D040641:Quantitative Trait Loci; D012307:Risk Factors; D012737:Sex Factors