Phenome-wide association study (Phewas) for detection of pleiotropy within variants associated with traits of the hematopoietic system and nonalcoholic fatty liver disease

CARLOS JOSE PIROLA; ADRIAN SALATINO; SILVIA C. SOOKOIAN

Boston, MA

Congreso; The 70th Annual Meeting of the American Association for the Study of Liver Diseases: The Liver Meeting 2019; 2019

The American Association for the Study of Liver Diseases (AASLD)

Background: GWAS of complex diseases, including NAFLD, have demonstrated that a large number of SNPs are implicated in the susceptibility of multiple traits, which is known as pleiotropy. Phenome-wide association studies-(PheWAS) become a powerful strategy to uncover pleiotropy. We tested the hypothesis of pleiotropy within variants associated with hematologic traits and NAFLD. We reasoned that a PheWas study on clinically meaningful traits may help to understand NAFLD biology.Methods: We leveraged information on electronic health records and GWAS data computed from 452,264 UK Biobank individuals, retrieved from the Gene ATLAS (http://geneatlas.roslin.ed.ac.uk) and Neale´s database (http://www.nealelab.is/uk-biobank/). We first searched for PheWas associations of variants influencing NAFLD, including PNPLA3-rs738409, TM6SF2-rs58542916, and HSD17B13-rs72613567. Based on the premise of reverse biology, the top significantly associated traits were further searched for genetic associations in the whole database. Results: Variants in the three loci above mentioned were significantly associated with blood cell-related traits (FDR