Genome-wide enrichment of TERT rare variants in Idiopathic Pulmonary Fibrosis patients of Latino ancestry
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Published version
Author(s)
Type
Journal Article
Abstract
Genome-wide rare variant studies of IPF patients of non-European ancestry have been understudied. Here, we evaluate the enrichment of rare genetic variants of 241 unrelated non-European cases, representing individuals of Latino, African, South Asian, East Asian, and Other Admixed ancestry. Gene burden analysis of deleterious rare (protein-truncating and missense) variants demonstrate an excess of TERT rare damaging variants (OR 67.1, 95% CI [23.1, 195.0], P = 9.4 x 10-14) in non-European subjects. Analysis by ancestry demonstrated an excess of rare, damaging TERT variants in the Latino subgroup (OR 80.9, 95% CI [17.3, 383.8], P = 2.6 x 10-8). Although the non-European group did not show enrichment of PARN, RTEL1, and KIF15 rare deleterious variants, these groups all showed a trend in the same direction as the European ancestry group. For TERT and KIF15, the inclusion of IPF patients of non-European ancestry led to a higher odds ratios and increased evidence in favor of rare deleterious variant contributions, thus demonstrating the increased power of multi-ethnic studies over single-ethnicity studies. To our knowledge, this is the first study that confirms the involvement of rare deleterious TERT variants for IPF patients of Latino and non-European ancestry. To better understand the genetic underpinnings of IPF patients of all ancestries, additional work will be needed to broaden patient recruitment to normalize imbalances.
Date Issued
2022-10-01
Date Acceptance
2022-06-03
Citation
American Journal of Respiratory and Critical Care Medicine, 2022, 206 (7), pp.903-905
ISSN
1073-449X
Publisher
American Thoracic Society
Start Page
903
End Page
905
Journal / Book Title
American Journal of Respiratory and Critical Care Medicine
Volume
206
Issue
7
Copyright Statement
© 2022 by the American Thoracic Society. This article is open access and distributed under the terms of the Creative Commons Attribution Non-Commercial No Derivatives License 4.0. For commercial usage and reprints, please e-mail Diane Gern (dgern@thoracic.org).
Sponsor
Action for Pulmonary Fibrosis
Identifier
https://www.ncbi.nlm.nih.gov/pubmed/35666822
Grant Number
n/a
Subjects
Genetics
IPF
Latino
Telomerase
non-European ancestry
Publication Status
Published
Coverage Spatial
United States
Date Publish Online
2022-06-06