title: Genes identified in Asian SLE GWASs are also associated with SLE in Caucasian populations.
abstract: Recent genome-wide association studies (GWASs) conducted in Asian populations have identified novel risk loci for systemic lupus erythematosus (SLE). Here, we genotyped 10 single-nucleotide polymorphisms (SNPs) in eight such loci and investigated their disease associations in three independent Caucasian SLE case-control cohorts recruited from Sweden, Finland and the United States. The disease associations of the SNPs in ETS1, IKZF1, LRRC18-WDFY4, RASGRP3, SLC15A4, TNIP1 and 16p11.2 were replicated, whereas no solid evidence of association was observed for the 7q11.23 locus in the Caucasian cohorts. SLC15A4 was significantly associated with renal involvement in SLE. The association of TNIP1 was more pronounced in SLE patients with renal and immunological disorder, which is corroborated by two previous studies in Asian cohorts. The effects of all the associated SNPs, either conferring risk for or being protective against SLE, were in the same direction in Caucasians and Asians. The magnitudes of the allelic effects for most of the SNPs were also comparable across different ethnic groups. On the contrary, remarkable differences in allele frequencies between Caucasian and Asian populations were observed for all associated SNPs. In conclusion, most of the novel SLE risk loci identified by GWASs in Asian populations were also associated with SLE in Caucasian populations. We observed both similarities and differences with respect to the effect sizes and risk allele frequencies across ethnicities.
authors.affiliation: Department of Medical Sciences, Molecular Medicine and Science for Life Laboratory, Uppsala University, Uppsala, Sweden.
authors.forename: Chuan
authors.initials: C
authors.lastname: Wang
authors.forename: Annika
authors.initials: A
authors.lastname: Ahlford
authors.forename: Tiina M
authors.initials: TM
authors.lastname: Järvinen
authors.forename: Gunnel
authors.initials: G
authors.lastname: Nordmark
authors.forename: Maija-Leena
authors.initials: ML
authors.lastname: Eloranta
authors.forename: Iva
authors.initials: I
authors.lastname: Gunnarsson
authors.forename: Elisabet
authors.initials: E
authors.lastname: Svenungsson
authors.forename: Leonid
authors.initials: L
authors.lastname: Padyukov
authors.forename: Gunnar
authors.initials: G
authors.lastname: Sturfelt
authors.forename: Andreas
authors.initials: A
authors.lastname: Jönsen
authors.forename: Anders A
authors.initials: AA
authors.lastname: Bengtsson
authors.forename: Lennart
authors.initials: L
authors.lastname: Truedsson
authors.forename: Catharina
authors.initials: C
authors.lastname: Eriksson
authors.forename: Solbritt
authors.initials: S
authors.lastname: Rantapää-Dahlqvist
authors.forename: Christopher
authors.initials: C
authors.lastname: Sjöwall
authors.forename: Heikki
authors.initials: H
authors.lastname: Julkunen
authors.forename: Lindsey A
authors.initials: LA
authors.lastname: Criswell
authors.forename: Robert R
authors.initials: RR
authors.lastname: Graham
authors.forename: Timothy W
authors.initials: TW
authors.lastname: Behrens
authors.forename: Juha
authors.initials: J
authors.lastname: Kere
authors.forename: Lars
authors.initials: L
authors.lastname: Rönnblom
authors.forename: Ann-Christine
authors.initials: AC
authors.lastname: Syvänen
authors.forename: Johanna K
authors.initials: JK
authors.lastname: Sandling
mesh_terms: D044466:Asian People / Q000235:genetics; D016022:Case-Control Studies; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D006801:Humans; D008180:Lupus Erythematosus, Systemic / Q000208:ethnology / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D044465:White People / Q000235:genetics