Phenome-wide association study using research participants' self-reported data provides insight into the Th17 and IL-17 pathway

• Published in: PloS one Vol. 12; no. 11; p. e0186405
• Main Authors: Ehm, Margaret G, Aponte, Jennifer L, Chiano, Mathias N, Yerges-Armstrong, Laura M, Johnson, Toby, Barker, Jonathan N, Cook, Suzanne F, Gupta, Akanksha, Hinds, David A, Li, Li, Nelson, Matthew R, Simpson, Michael A, Tian, Chao, McCarthy, Linda C, Rajpal, Deepak K, Waterworth, Dawn M
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 01-11-2017; Public Library of Science (PLoS)
• Subjects: Acne; Allergies; Analysis; Arthritis; Assessments; Autoimmune diseases; Biology and Life Sciences; Care and treatment; Dermatology; Diagnosis; Disease; Drug delivery; Drugs; Electronic health records; Gene loci; Genetic Predisposition to Disease; Genetics; Genome-Wide Association Study; Genomes; Genomics; Helper cells; Humans; Interleukin 17; Interleukin-17 - genetics; Interleukin-17 - immunology; Life sciences; Lymphocytes T; Medical records; Medicine; Medicine and Health Sciences; Pharynx; Phenotype; Psoriasis; R&D; Research & development; Self Report; Self-rated health; Studies; Th17 Cells - immunology; Tonsillectomy; Tyk2 protein
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0186405

A phenome-wide association study of variants in genes in the Th17 and IL-17 pathway was performed using self-reported phenotypes and genetic data from 521,000 research participants of 23andMe. Results replicated known associations with similar effect sizes for autoimmune traits illustrating self-reported traits can be a surrogate for clinically assessed conditions. Novel associations controlling for a false discovery rate of 5% included the association of the variant encoding p.Ile684Ser in TYK2 with increased risk of tonsillectomy, strep throat occurrences and teen acne, the variant encoding p.Arg381Gln in IL23R with a decrease in dandruff frequency, the variant encoding p.Asp10Asn in TRAF3IP2 with risk of male-pattern balding, and the RORC regulatory variant (rs4845604) with protection from allergies. This approach enabled rapid assessment of association with a wide variety of traits and investigation of traits with limited reported associations to overlay meaningful phenotypic context on the range of conditions being considered for drugs targeting this pathway.