Meta-analysis of genome-wide linkage studies of systemic lupus erythematosus.
A genetic contribution to the development of systemic lupus erythematosus (SLE) is well established. Several genome-wide linkage scans have identified a number of putative susceptibility loci for SLE, some of which have been replicated in independent samples. This study aimed to identify the regions showing the most consistent evidence for linkage by applying the genome scan meta-analysis (GSMA) method. The study identified two genome-wide suggestive regions on 6p21.1-q15 and 20p11-q13.13 (P-value=0.0056 and P-value=0.0044, respectively) and a region with P-value<0.01 on 16p13-q12.2. The region on chromosome 6 contains the human leukocyte antigen cluster, and the chromosome 16 and 20 regions have been replicated in several cohorts. The potential importance of the identified genomic regions are also highlighted. These results, in conjunction with data emerging from dense single nucleotide polymorphism typing of specific regions or future genome-wide association studies will help guide efforts to identify the actual predisposing genetic variation contributing to this complex genetic disease.
Forabosco
P
P
Department of Medical and Molecular Genetics, King's College London School of Medicine at Guy's, King's College and St Thomas' Hospitals, London, UK.
Gorman
J D
JD
Cleveland
C
C
Kelly
J A
JA
Fisher
S A
SA
Ortmann
W A
WA
Johansson
C
C
Johanneson
B
B
Moser
K L
KL
Gaffney
P M
PM
Tsao
B P
BP
Cantor
R M
RM
Alarcón-Riquelme
M E
ME
Behrens
T W
TW
Harley
J B
JB
Lewis
C M
CM
Criswell
L A
LA
D002885:Chromosomes, Human, Pair 16 / Q000235:genetics; D002890:Chromosomes, Human, Pair 20 / Q000235:genetics; D002896:Chromosomes, Human, Pair 6 / Q000235:genetics; D005260:Female; D008040:Genetic Linkage; D020022:Genetic Predisposition to Disease; D015894:Genome, Human; D006680:HLA Antigens / Q000235:genetics; D006801:Humans; D008180:Lupus Erythematosus, Systemic / Q000235:genetics* / Q000276:immunology; D008297:Male
D006680:HLA Antigens