TY - JOUR
T1 - Genome-wide pooling approach identifies SPATA5 as a new susceptibility locus for alopecia areata
AU - Forstbauer, Lina M
AU - Brockschmidt, Felix F
AU - Moskvina, Valentina
AU - Herold, Christine
AU - Redler, Silke
AU - Herzog, Alexandra
AU - Hillmer, Axel M
AU - Meesters, Christian
AU - Heilmann, Stefanie
AU - Albert, Florian
AU - Alblas, Margrieta
AU - Hanneken, Sandra
AU - Eigelshoven, Sibylle
AU - Giehl, Kathrin A
AU - Jagielska, Dagny
AU - Blume-Peytavi, Ulrike
AU - Garcia Bartels, Natalie
AU - Kuhn, Jennifer
AU - Hennies, Hans Christian
AU - Goebeler, Matthias
AU - Jung, Andreas
AU - Peitsch, Wiebke K
AU - Kortüm, Anne-Katrin
AU - Moll, Ingrid
AU - Kruse, Roland
AU - Lutz, Gerhard
AU - Wolff, Hans
AU - Blaumeiser, Bettina
AU - Böhm, Markus
AU - Kirov, George
AU - Becker, Tim
AU - Nöthen, Markus M
AU - Betz, Regina C
PY - 2012/3
Y1 - 2012/3
N2 - 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.
AB - 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.
KW - Alleles
KW - Alopecia Areata
KW - Case-Control Studies
KW - Follow-Up Studies
KW - Genetic Loci
KW - Genetic Predisposition to Disease
KW - Genome-Wide Association Study
KW - Genotype
KW - Humans
KW - Polymorphism, Single Nucleotide
KW - Reproducibility of Results
KW - Journal Article
KW - Research Support, Non-U.S. Gov't
UR - https://www.nature.com/ejhg/
U2 - 10.1038/ejhg.2011.185
DO - 10.1038/ejhg.2011.185
M3 - Article
C2 - 22027810
VL - 20
SP - 326
EP - 332
JO - European Journal of Human Genetics
JF - European Journal of Human Genetics
SN - 1018-4813
IS - 3
ER -