Family recurrence risk of alopecia areata in the Faroe Islands.

BACKGROUND: Reports of a positive family history of alopecia areata (AA) have led to the assumption of a genetic component. The Faroe Islands population is small, has been isolated until the 20th century, and is served by only one dermatology clinic, making it highly suitable for genealogical studies. AIM: To determine the incidence of AA and to estimate the recurrence risk ratio (RRR) in five generations and in a nationwide dermatologist-based AA cohort using the Faroese genealogy database. METHODS: All registered cases of AA during the period 1973-2011 were identified from the Faroese national dermatology clinics. The AA cases were linked with the genealogy database covering the entire Faroese population, and the probability of AA among first-, second- and third-degree relatives was calculated. RESULTS: In total, 178 cases of AA were identified, giving a crude incidence of 10.1 per 100 000 person-years (10.9 for women and 9.4 for men). The cumulative incidence proportion over life was 0.8%. There was no apparent trend in the probabilities for AA in first-degree family members compared with second- and third-degree relatives. RRR was > 1 in second-degree family members only. CONCLUSION: A lower prevalence rate of AA was found than previously published. The genealogical study failed to identify any apparent trend in the RRR estimates, questioning the role of genetic factors in AA in the Faroe Islands. However, it is possible that the trend is masked by bias and low power; larger studies are therefore warranted to estimate the heritability of AA.

Whole-exome sequencing of individuals from an isolated population implicates rare risk variants in bipolar disorder.

Bipolar disorder affects about 1% of the world's population, and its estimated heritability is about 75%. Only few whole genome or whole-exome sequencing studies in bipolar disorder have been reported, and no rare coding variants have yet been robustly identified. The use of isolated populations might help finding variants with a recent origin, more likely to have drifted to higher frequency by chance. Following this approach, we investigated 28 bipolar cases and 214 controls from the Faroe Islands by whole exome sequencing, and the results were followed-up in a British sample of 2025 cases and 1358 controls. Seventeen variants in 16 genes in the single-variant analysis, and 3 genes in the gene-based statistics surpassed exome-wide significance in the discovery phase. The discovery findings were supported by enrichment analysis of common variants from genome-wide association studies (GWAS) data and interrogation of protein-protein interaction networks. The replication in the British sample confirmed the association with NOS1 (missense variant rs79487279) and NCL (gene-based test). A number of variants from the discovery set were not present in the replication sample, including a novel PITPNM2 missense variant, which is located in a highly significant schizophrenia GWAS locus. Likewise, PIK3C2A identified in the gene-based analysis is located in a combined bipolar and schizophrenia GWAS locus. Our results show support both for existing findings in the literature, as well as for new risk genes, and identify rare variants that might provide additional information on the underlying biology of bipolar disorder.