6”-O-Malonylgenistin

22027810

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.

alopecia areata, genome-wide association study, autoimmunity, hair loss

Genome-wide pooling approach identifies SPATA5 as a new susceptibility locus for alopecia areata

Lina M Forstbauer,1,20 Felix F Brockschmidt,1,2,20 Valentina Moskvina,3 Christine Herold,4 Silke Redler,1 Alexandra Herzog,1 Axel M Hillmer,5 Christian Meesters,4,6 Stefanie Heilmann,1,2 Florian Albert,1 Margrieta Alblas,1,2 Sandra Hanneken,7 Sibylle Eigelshoven,7 Kathrin A Giehl,8 Dagny Jagielska,1,9 Ulrike Blume-Peytavi,9 Natalie Garcia Bartels,9 Jennifer Kuhn,10,11,12 Hans Christian Hennies,10,11,12 Matthias Goebeler,13 Andreas Jung,13 Wiebke K Peitsch,14 Anne-Katrin Kortum,15 Ingrid Moll,15 Roland Kruse,16 Gerhard Lutz,17 Hans Wolff,7 Bettina Blaumeiser,18 Markus Bohm,19 George Kirov,3 Tim Becker,4,6 Markus M Nothen,1,2 and Regina C Betz1,*

2012 Mar

21847142

We aimed at identifying transcripts whose expression is regulated by a SNP-SNP interaction. Out of 47 294 expression phenotypes we used 3107 transcripts that survived an extensive quality control and 86 613 linkage disequilibrium-pruned SNP markers that have been genotyped in 210 individuals. For each transcript we defined cis-SNPs, tested them for epistasis with all trans-SNPs, and corrected all observed cis-trans-regulated expression effects for multiple testing. We determined that the expression of about 15% of all included transcripts is regulated by a significant two-locus interaction, which is more than expected (P=2.86 × 10−144). Our findings suggest further that cis-markers with so called ‘marginal effects’ are more likely to be involved in two-locus gene regulation than expected (P=8.27 × 10−05), although the majority of interacting cis-markers showed no one-locus regulation. Furthermore, we found evidence that gene-mediated trans-effects are not a major source of epistasis, as no enrichment of genes has been found in close vicinity of trans-SNPs. In addition, our data support the notion that neither chromosomal regions nor cellular processes are enriched in epistatic interactions. Finally, some of the cis-trans regulated genes have been found in genome-wide association studies, which might be interesting for follow-up studies of the corresponding disorders. In summary, our results provide novel insights into the complex genome-transcriptome regulation.

eQTLs, epistasis, interaction, cis-regulation, trans-regulation

A systematic eQTL study of cis-trans epistasis in 210 HapMap individuals

Jessica Becker,1,2,4 Jens R Wendland,3,4 Britta Haenisch,1,2 Markus M Nothen,1,2 and Johannes Schumacher2,*

2012 Jan;