Genome-wide pooling approach identifies SPATA5 as a new susceptibility locus for alopecia areata.
Alopecia areata (AA) is a common hair loss disorder, which is thought to be a tissue-specific autoimmune disease. Previous research has identified a few AA susceptibility genes, most of which are implicated in autoimmunity. To identify new genetic variants and further elucidate the genetic basis of AA, we performed a genome-wide association study using the strategy of pooled DNA genotyping (729 cases, 656 controls). The strongest association was for variants in the HLA region, which confirms the validity of the pooling strategy. The selected top 61 single-nucleotide polymorphisms (SNPs) were analyzed in an independent replication sample (454 cases, 1364 controls). Only one SNP outside of the HLA region (rs304650) showed significant association. This SNP was then analyzed in a second independent replication sample (537 cases, 657 controls). The finding was not replicated on a significant level, but showed the same tendency. A combined analysis of the two replication samples was then performed, and the SNP rs304650 showed significant association with P=3.43 × 10(-4) (OR=1.24 (1.10-1.39)). This SNP maps to an intronic region of the SPATA5 (spermatogenesis-associated protein 5) gene on chromosome 4. The results therefore suggest the SPATA5 locus is a new susceptibility locus for AA.
Institute of Human Genetics, University of Bonn, Bonn, Germany.
Lina M
LM
Forstbauer
Felix F
FF
Brockschmidt
Valentina
V
Moskvina
Christine
C
Herold
Silke
S
Redler
Alexandra
A
Herzog
Axel M
AM
Hillmer
Christian
C
Meesters
Stefanie
S
Heilmann
Florian
F
Albert
Margrieta
M
Alblas
Sandra
S
Hanneken
Sibylle
S
Eigelshoven
Kathrin A
KA
Giehl
Dagny
D
Jagielska
Ulrike
U
Blume-Peytavi
Natalie
N
Garcia Bartels
Jennifer
J
Kuhn
Hans Christian
HC
Hennies
Matthias
M
Goebeler
Andreas
A
Jung
Wiebke K
WK
Peitsch
Anne-Katrin
AK
Kortüm
Ingrid
I
Moll
Roland
R
Kruse
Gerhard
G
Lutz
Hans
H
Wolff
Bettina
B
Blaumeiser
Markus
M
Böhm
George
G
Kirov
Tim
T
Becker
Markus M
MM
Nöthen
Regina C
RC
Betz
D000483:Alleles; D000506:Alopecia Areata / Q000235:genetics*; D016022:Case-Control Studies; D005500:Follow-Up Studies; D056426:Genetic Loci; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D005838:Genotype; D006801:Humans; D020641:Polymorphism, Single Nucleotide; D015203:Reproducibility of Results