Whole genome sequence association with E-selectin levels reveals loss-of-function variant in African Americans

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.

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Publication Details

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UNC Libraries
Published
2025-08-13
DOI
https://doi.org/10.17615/vydg-8h18
Primary Topic
Cell Adhesion Molecules Research
Type
article
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article

Whole genome sequence association with E-selectin levels reveals loss-of-function variant in African Americans

Linda M. Polfus, Xue Zhong, Amanda Miller, Biqi Wang et al.
UNC Libraries
Cell Adhesion Molecules Research
article

Whole genome sequence association with E-selectin levels reveals loss-of-function variant in African Americans

Linda M. Polfus, Xue Zhong, Amanda Miller, Biqi Wang, Ruth J. F. Loos, Nancy S. Jenny, Russell Paul Bowler, Adolfo Correa, NHLBI Trans-Omics for Precision Medicine Consortium, Marsha M. Wheeler, Bingshan Li, Nathan Pankratz, Laura M. Raffield, Girish N. Nadkarni, Russell P. Tracy, Arden Moscati, Lisheng Zhou, Joshua C. Bis, Jill M. Johnsen, Michael Preuß, Alex P. Reiner, Guillaume Lettre, Shabnam Salimi, Paul L. Auer, Leslie A. Lange, Deborah A. Nickerson
article en

Abstract

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.

UNC Libraries
University of North Carolina at Chapel Hill (US)
Openalex Percentile: Top 63%
Cell Adhesion Molecules Research
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