title: Genome-wide association scan in women with systemic lupus erythematosus identifies susceptibility variants in ITGAM, PXK, KIAA1542 and other loci.
abstract: Systemic lupus erythematosus (SLE) is a common systemic autoimmune disease with complex etiology but strong clustering in families (lambda(S) = approximately 30). We performed a genome-wide association scan using 317,501 SNPs in 720 women of European ancestry with SLE and in 2,337 controls, and we genotyped consistently associated SNPs in two additional independent sample sets totaling 1,846 affected women and 1,825 controls. Aside from the expected strong association between SLE and the HLA region on chromosome 6p21 and the previously confirmed non-HLA locus IRF5 on chromosome 7q32, we found evidence of association with replication (1.1 x 10(-7) < P(overall) < 1.6 x 10(-23); odds ratio = 0.82-1.62) in four regions: 16p11.2 (ITGAM), 11p15.5 (KIAA1542), 3p14.3 (PXK) and 1q25.1 (rs10798269). We also found evidence for association (P < 1 x 10(-5)) at FCGR2A, PTPN22 and STAT4, regions previously associated with SLE and other autoimmune diseases, as well as at > or =9 other loci (P < 2 x 10(-7)). Our results show that numerous genes, some with known immune-related functions, predispose to SLE.
authors.affiliation: Oklahoma Medical Research Foundation, 825 NE 13th Street, Oklahoma City, Oklahoma 73104, USA. SLEGEN@wfubmc.edu
authors.forename: John B
authors.initials: JB
authors.lastname: Harley
authors.forename: Marta E
authors.initials: ME
authors.lastname: Alarcón-Riquelme
authors.forename: Lindsey A
authors.initials: LA
authors.lastname: Criswell
authors.forename: Chaim O
authors.initials: CO
authors.lastname: Jacob
authors.forename: Robert P
authors.initials: RP
authors.lastname: Kimberly
authors.forename: Kathy L
authors.initials: KL
authors.lastname: Moser
authors.forename: Betty P
authors.initials: BP
authors.lastname: Tsao
authors.forename: Timothy J
authors.initials: TJ
authors.lastname: Vyse
authors.forename: Carl D
authors.initials: CD
authors.lastname: Langefeld
authors.forename: Swapan K
authors.initials: SK
authors.lastname: Nath
authors.forename: Joel M
authors.initials: JM
authors.lastname: Guthridge
authors.forename: Beth L
authors.initials: BL
authors.lastname: Cobb
authors.forename: Daniel B
authors.initials: DB
authors.lastname: Mirel
authors.forename: Miranda C
authors.initials: MC
authors.lastname: Marion
authors.forename: Adrienne H
authors.initials: AH
authors.lastname: Williams
authors.forename: Jasmin
authors.initials: J
authors.lastname: Divers
authors.forename: Wei
authors.initials: W
authors.lastname: Wang
authors.forename: Summer G
authors.initials: SG
authors.lastname: Frank
authors.forename: Bahram
authors.initials: B
authors.lastname: Namjou
authors.forename: Stacey B
authors.initials: SB
authors.lastname: Gabriel
authors.forename: Annette T
authors.initials: AT
authors.lastname: Lee
authors.forename: Peter K
authors.initials: PK
authors.lastname: Gregersen
authors.forename: Timothy W
authors.initials: TW
authors.lastname: Behrens
authors.forename: Kimberly E
authors.initials: KE
authors.lastname: Taylor
authors.forename: Michelle
authors.initials: M
authors.lastname: Fernando
authors.forename: Raphael
authors.initials: R
authors.lastname: Zidovetzki
authors.forename: Patrick M
authors.initials: PM
authors.lastname: Gaffney
authors.forename: Jeffrey C
authors.initials: JC
authors.lastname: Edberg
authors.forename: John D
authors.initials: JD
authors.lastname: Rioux
authors.forename: Joshua O
authors.initials: JO
authors.lastname: Ojwang
authors.forename: Judith A
authors.initials: JA
authors.lastname: James
authors.forename: Joan T
authors.initials: JT
authors.lastname: Merrill
authors.forename: Gary S
authors.initials: GS
authors.lastname: Gilkeson
authors.forename: Michael F
authors.initials: MF
authors.lastname: Seldin
authors.forename: Hong
authors.initials: H
authors.lastname: Yin
authors.forename: Emily C
authors.initials: EC
authors.lastname: Baechler
authors.forename: Quan-Zhen
authors.initials: QZ
authors.lastname: Li
authors.forename: Edward K
authors.initials: EK
authors.lastname: Wakeland
authors.forename: Gail R
authors.initials: GR
authors.lastname: Bruner
authors.forename: Kenneth M
authors.initials: KM
authors.lastname: Kaufman
authors.forename: Jennifer A
authors.initials: JA
authors.lastname: Kelly
mesh_terms: D000483:Alleles; D019540:Area Under Curve; D039481:CD11b Antigen / Q000235:genetics*; D016022:Case-Control Studies; D002878:Chromosomes, Human, Pair 1; D002880:Chromosomes, Human, Pair 11; D002885:Chromosomes, Human, Pair 16; D002893:Chromosomes, Human, Pair 3; D002896:Chromosomes, Human, Pair 6; D015331:Cohort Studies; D016001:Confidence Intervals; D005260:Female; D005819:Genetic Markers; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D015894:Genome, Human; D006680:HLA Antigens / Q000235:genetics; D006239:Haplotypes; D006801:Humans; D050835:Interferon Regulatory Factors / Q000235:genetics; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics*; D015810:Linkage Disequilibrium; D016015:Logistic Models; D008180:Lupus Erythematosus, Systemic / Q000235:genetics* / Q000276:immunology; D009419:Nerve Tissue Proteins / Q000235:genetics*; D016017:Odds Ratio; D020641:Polymorphism, Single Nucleotide; D017346:Protein Serine-Threonine Kinases / Q000235:genetics*; D054596:Protein Tyrosine Phosphatase, Non-Receptor Type 22 / Q000235:genetics; D012372:ROC Curve; D012307:Risk Factors; D050797:STAT4 Transcription Factor / Q000235:genetics; D044465:White People
chemical_list: D039481:CD11b Antigen; D005819:Genetic Markers; D006680:HLA Antigens; C431713:IRF5 protein, human; C509295:ITGAM protein, human; D050835:Interferon Regulatory Factors; D047908:Intracellular Signaling Peptides and Proteins; D009419:Nerve Tissue Proteins; D050797:STAT4 Transcription Factor; C494090:STAT4 protein, human; C508327:PXK protein, human; D017346:Protein Serine-Threonine Kinases; C516765:PTPN22 protein, human; D054596:Protein Tyrosine Phosphatase, Non-Receptor Type 22