Imputation provides an opportunity to study filaggrin (FLG) null mutations in large population cohorts that lack bespoke genotyping

Background: Low frequency mutations within the filaggrin (FLG) gene are established genetic risk factors for atopic dermatitis. Studies of FLG have typically used sequencing or bespoke genotyping. Large-scale population cohorts with genome-wide imputed data offer powerful analysis opportunities, but FLG genotyping is often not feasible in such studies. Therefore, we aimed to determine quality of selected FLG null genotype extracted from sources, focussing on UK data. Methods: We compared allele frequencies three (R501X, R2447X and S3247X) directly genotyped ALSPAC cohort. Logistic regression was test association dermatitis Biobank investigate usefulness Results: The appear be well datasets that use Haplotype Reference Consortium (HRC) imputation (0.3% discordance data). However, a greater proportion alleles failed wild-type alleles. Despite calling being imperfect, they still strongly associated (p-values between 7x10-10 5x10-75 Biobank). Conclusions: HRC appears adequate population-based mutations.