title: Identification of a systemic lupus erythematosus susceptibility locus at 11p13 between PDHX and CD44 in a multiethnic study.
abstract: Systemic lupus erythematosus (SLE) is considered to be the prototypic autoimmune disease, with a complex genetic architecture influenced by environmental factors. We sought to replicate a putative association at 11p13 not yet exceeding genome-wide significance (p < 5 × 10(-8)) identified in a genome-wide association study (GWAS). Our GWA scan identified two intergenic SNPs located between PDHX and CD44 showing suggestive evidence of association with SLE in cases of European descent (rs2732552, p = 0.004, odds ratio [OR] = 0.78; rs387619, p = 0.003, OR = 0.78). The replication cohort consisted of >15,000 subjects, including 3562 SLE cases and 3491 controls of European ancestry, 1527 cases and 1811 controls of African American (AA) descent, and 1265 cases and 1260 controls of Asian origin. We observed robust association at both rs2732552 (p = 9.03 × 10(-8), OR = 0.83) and rs387619 (p = 7.7 × 10(-7), OR = 0.83) in the European samples with p(meta) = 1.82 × 10(-9) for rs2732552. The AA and Asian SLE cases also demonstrated association at rs2732552 (p = 5 × 10(-3), OR = 0.81 and p = 4.3 × 10(-4), OR = 0.80, respectively). A meta-analysis of rs2732552 for all racial and ethnic groups studied produced p(meta) = 2.36 × 10(-13). This locus contains multiple regulatory sites that could potentially affect expression and functions of CD44, a cell-surface glycoprotein influencing immunologic, inflammatory, and oncologic phenotypes, or PDHX, a subunit of the pyruvate dehydrogenase complex.
authors.affiliation: Arthritis and Clinical Immunology Research Program, Oklahoma Medical Research Foundation, Oklahoma City, OK 73104, USA.
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Lessard
authors.forename: Indra
authors.initials: I
authors.lastname: Adrianto
authors.forename: Jennifer A
authors.initials: JA
authors.lastname: Kelly
authors.forename: Kenneth M
authors.initials: KM
authors.lastname: Kaufman
authors.forename: Kiely M
authors.initials: KM
authors.lastname: Grundahl
authors.forename: Adam
authors.initials: A
authors.lastname: Adler
authors.forename: Adrienne H
authors.initials: AH
authors.lastname: Williams
authors.forename: Caroline J
authors.initials: CJ
authors.lastname: Gallant
authors.forename: Juan-Manuel
authors.initials: JM
authors.lastname: Anaya
authors.forename: Sang-Cheol
authors.initials: SC
authors.lastname: Bae
authors.forename: Susan A
authors.initials: SA
authors.lastname: Boackle
authors.forename: Elizabeth E
authors.initials: EE
authors.lastname: Brown
authors.forename: Deh-Ming
authors.initials: DM
authors.lastname: Chang
authors.forename: Lindsey A
authors.initials: LA
authors.lastname: Criswell
authors.forename: Jeffrey C
authors.initials: JC
authors.lastname: Edberg
authors.forename: Barry I
authors.initials: BI
authors.lastname: Freedman
authors.forename: Peter K
authors.initials: PK
authors.lastname: Gregersen
authors.forename: Gary S
authors.initials: GS
authors.lastname: Gilkeson
authors.forename: Chaim O
authors.initials: CO
authors.lastname: Jacob
authors.forename: Judith A
authors.initials: JA
authors.lastname: James
authors.forename: Diane L
authors.initials: DL
authors.lastname: Kamen
authors.forename: Robert P
authors.initials: RP
authors.lastname: Kimberly
authors.forename: Javier
authors.initials: J
authors.lastname: Martin
authors.forename: Joan T
authors.initials: JT
authors.lastname: Merrill
authors.forename: Timothy B
authors.initials: TB
authors.lastname: Niewold
authors.forename: So-Yeon
authors.initials: SY
authors.lastname: Park
authors.forename: Michelle A
authors.initials: MA
authors.lastname: Petri
authors.forename: Bernardo A
authors.initials: BA
authors.lastname: Pons-Estel
authors.forename: Rosalind
authors.initials: R
authors.lastname: Ramsey-Goldman
authors.forename: John D
authors.initials: JD
authors.lastname: Reveille
authors.forename: Yeong Wook
authors.initials: YW
authors.lastname: Song
authors.forename: Anne M
authors.initials: AM
authors.lastname: Stevens
authors.forename: Betty P
authors.initials: BP
authors.lastname: Tsao
authors.forename: Luis M
authors.initials: LM
authors.lastname: Vila
authors.forename: Timothy J
authors.initials: TJ
authors.lastname: Vyse
authors.forename: Chack-Yung
authors.initials: CY
authors.lastname: Yu
authors.forename: Joel M
authors.initials: JM
authors.lastname: Guthridge
authors.forename: Gail R
authors.initials: GR
authors.lastname: Bruner
authors.forename: Carl D
authors.initials: CD
authors.lastname: Langefeld
authors.forename: Courtney
authors.initials: C
authors.lastname: Montgomery
authors.forename: John B
authors.initials: JB
authors.lastname: Harley
authors.forename: R Hal
authors.initials: RH
authors.lastname: Scofield
authors.forename: Patrick M
authors.initials: PM
authors.lastname: Gaffney
authors.forename: Kathy L
authors.initials: KL
authors.lastname: Moser
mesh_terms: D001741:Black or African American / Q000235:genetics; D044467:American Indian or Alaska Native / Q000235:genetics; D044466:Asian People / Q000235:genetics; D002880:Chromosomes, Human, Pair 11 / Q000235:genetics*; D015331:Cohort Studies; D005260:Female; D056426:Genetic Loci; D020022:Genetic Predisposition to Disease; D006239:Haplotypes; D006630:Hispanic or Latino / Q000235:genetics; D006801:Humans; D018960:Hyaluronan Receptors / Q000235:genetics*; D015810:Linkage Disequilibrium; D008180:Lupus Erythematosus, Systemic / Q000208:ethnology / Q000235:genetics*; D008297:Male; D020641:Polymorphism, Single Nucleotide; D011768:Pyruvate Dehydrogenase Complex / Q000235:genetics*; D044465:White People / Q000235:genetics
chemical_list: D018960:Hyaluronan Receptors; C045867:PDHX protein, human; D011768:Pyruvate Dehydrogenase Complex