Alopecia areata (AA) is a highly prevalent autoimmune disease that attacks the hair follicle and leads to hair loss that can range from small patches to complete loss of scalp and body hair. Our previous linkage and genome‐wide association studies (GWAS) generated strong evidence for aetiological contributions from inherited genetic variants at different population frequencies, including both rare mutations and common polymorphisms. Additionally, we conducted gene expression (GE) studies on scalp biopsies of 96 patients and controls to establish signatures of active disease. In this study, we performed an integrative analysis on these two datasets to test the hypothesis that rare CNVs in patients with AA could be leveraged to identify drivers of disease in our AA GE signatures. We analysed copy number variants (CNVs) in a case‐control cohort of 673 patients with AA and 16 311 controls independent of the case‐control cohort of 96 research participants used in our GE study. Using an integrative computational analysis, we identified 14 genes whose expression levels were altered by CNVs in a consistent direction of effect, corresponding to gene expression changes in lesional skin of patients. Four of these genes were affected by CNVs in three or more unrelated patients with AA, including ATG4B and SMARCA2, which are involved in autophagy and chromatin remodelling, respectively. Our findings identified new classes of genes with potential contributions to AA pathogenesis.

Computational study of energy filtering effects in one-dimensional composite nano-structures J. Appl. Phys. 111, 024508 (2012) Studies of pure and nitrogen-incorporated hydrogenated amorphous carbon thin films and their possible application for amorphous silicon solar cells J. Appl. Phys. 111, 014908 (2012) Thin film contact resistance with dissimilar materials Deposition of vertical, cone-shaped plasmonic nanorod arrays onto sub-50 nm polythiophene films on Ag substrates is shown to result in significant absorption enhancement (>12 at the polythiophene band edge) and spectral broadening (more than 250 nm increase) relative to polythiophene/Ag films without plasmonic nanorod arrays. Full-field electromagnetic simulations are used to identify the modes of the plasmonic nanorod array/polythiophene/Ag film system. Both gap modes and longitudinal monopole antenna modes give rise to highly localized electric fields in the polythiophene film and are the primary contributors to polythiophene absorption enhancement. This approach is suitable for large area optoelectronic applications where light management in ultrathin active layers is desired.

The primary forms of cicatricial (scarring) alopecia (PCA) are a group of inflammatory, irreversible hair loss disorders characterized by immune cell infiltrates targeting hair follicles (HFs). Lichen planopilaris (LPP), frontal fibrosing alopecia (FFA) and centrifugal cicatricial alopecia (CCCA) are among the main subtypes of PCAs. The pathogenesis of the different types of PCAs are poorly understood, and current treatment regimens yield inconsistent and unsatisfactory results. We performed high-throughput RNA-sequencing on scalp biopsies of a large cohort PCA patients to develop gene expression-based signatures, trained into machine-learning based predictive models and pathways associated with dysregulated gene expression. We performed morphological and cytokine analysis to define the immune cell populations found in PCA subtypes. We identified a common PCA gene signature that was shared between LPP, FFA, and CCCA which revealed a significant over-representation of mast cell genes, as well as downregulation of cholesterogenic pathways and upregulation of fibrosis and immune signaling genes. Immunohistological analyses revealed an increased presence of mast cells in PCAs lesions. Our gene expression analyses revealed common pathways associated with PCAs, with a strong association with mast cells. The indistinguishable differences in gene expression profiles and immune cell signatures between LPP, FFA and CCCA suggest that similar treatment regimens may be effective in treating these irreversible forms of hair loss.

Alopecia areata is a complex genetic disease that results in hair loss due to the autoimmune-mediated attack of the hair follicle. We previously defined a role for both rare and common variants in our earlier GWAS and linkage studies. Here, we identify rare variants contributing to Alopecia Areata using a whole exome sequencing and gene-level burden analyses approach on 849 Alopecia Areata patients compared to 15,640 controls. KRT82 is identified as an Alopecia Areata risk gene with rare damaging variants in 51 heterozygous Alopecia Areata individuals (6.01%), achieving genome-wide significance (p = 2.18E−07). KRT82 encodes a hair-specific type II keratin that is exclusively expressed in the hair shaft cuticle during anagen phase, and its expression is decreased in Alopecia Areata patient skin and hair follicles. Finally, we find that cases with an identified damaging KRT82 variant and reduced KRT82 expression have elevated perifollicular CD8 infiltrates. In this work, we utilize whole exome sequencing to successfully identify a significant Alopecia Areata disease-relevant gene, KRT82, and reveal a proposed mechanism for rare variant predisposition leading to disrupted hair shaft integrity.