Whole genome sequence association with E-selectin levels reveals loss-of-function variant in African Americans. Hum Mol Genet 2019 Feb 01;28(3):515-523
Date
10/12/2018Pubmed ID
30307499Pubmed Central ID
PMC6337694DOI
10.1093/hmg/ddy360Scopus ID
2-s2.0-85060178763 (requires institutional sign-in at Scopus site) 12 CitationsAbstract
E-selectin mediates the rolling of circulating leukocytes during inflammatory processes. Previous genome-wide association studies in European and Asian individuals have identified the ABO locus associated with E-selectin levels. Using Trans-Omics for Precision Medicine whole genome sequencing data in 2249 African Americans (AAs) from the Jackson Heart Study, we examined genome-wide associations with soluble E-selectin levels. In addition to replicating known signals at ABO, we identified a novel association of a common loss-of-function, missense variant in Fucosyltransferase 6 (FUT6; rs17855739,p.Glu274Lys, P = 9.02 × 10-24) with higher soluble E-selectin levels. This variant is considerably more common in populations of African ancestry compared to non-African ancestry populations. We replicated the association of FUT6 p.Glu274Lys with higher soluble E-selectin in an independent population of 748 AAs from the Women's Health Initiative and identified an additional pleiotropic association with vitamin B12 levels. Despite the broad role of both selectins and fucosyltransferases in various inflammatory, immune and cancer-related processes, we were unable to identify any additional disease associations of the FUT6 p.Glu274Lys variant in an electronic medical record-based phenome-wide association scan of over 9000 AAs.
Author List
Polfus LM, Raffield LM, Wheeler MM, Tracy RP, Lange LA, Lettre G, Miller A, Correa A, Bowler RP, Bis JC, Salimi S, Jenny NS, Pankratz N, Wang B, Preuss MH, Zhou L, Moscati A, Nadkarni GN, Loos RJF, Zhong X, Li B, Johnsen JM, Nickerson DA, Reiner AP, Auer PL, NHLBI Trans-Omics for Precision Medicine ConsortiumAuthor
Paul L. Auer PhD Professor in the Institute for Health and Equity department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
AdultE-Selectin
Female
Fucosyltransferases
Genetic Predisposition to Disease
Genome-Wide Association Study
Humans
Male
Polymorphism, Single Nucleotide
Whole Genome Sequencing