The document summarizes research on identifying genetic risk factors for alopecia areata. It describes analyzing genetic data from over 700 patients to identify 64 candidate genes and 701 variants potentially involved in monogenic causes. Pathway analysis found these genes enriched for extracellular matrix functions. Further studies will validate co-segregation of variants in families and test for genetic burden using exome data from 10,000 controls. The research aims to elucidate pathogenesis by studying extracellular matrix integrity and signaling in patient samples.
11. Results: Variant Filtering
10,000,000
373
6,688
SNPs Genes
11,272
300,000
Mutations
In the genome.
Genotyped TagSNPs
with evidence for linkage
and family-based association.
SNPs tagged by 373 SNPs.
Exome mutations (f<.05) in proband that alters protein sequence
and in a region with evidence for cosegregation with AA in proband’s family
~18,000
619
179
Genotype 38 families in discovery cohort
Exome sequence 28 probands in discovery cohort
223
148
108
87
Same mutation (f<.05) seen in replication cohort
Exome sequence replication cohort of 108 probands
New mutation (f<.001) in a same gene in replication cohort
5843
Exome sequence in a cohort of nonfamilial 620 patients
10349
16168union
49664New mutation (f<.001) in a same gene in replication cohort
701
14. Acknowledgements
National Alopecia Areata Registry
Angela Christiano
Vera Price
Maria Hordinsky
David Norris
Madeline Duvic
NIAMS 1P30 AR069632-01
NIAMS 1P50 AR070588-01
Christiano Lab
Stephanie Erjavec
Alexa Abdelaziz
Tarek Yammany
Angela M. Christiano
AACORT core services
Sahar Gelfman
Aris Floratos
The Feinstein Institute for Medical Research
Annette Lee
Peter Gregersen
Baylor College of Medicine
Wei V. Chen
Christopher Amos