Genetic Ancestry-Smoking Interactions and Lung Function in African Americans: A Cohort Study

Melinda C Aldrich,Laura A Colangelo,Donglei Hu,Marilyn G Foreman,Yongmei Liu,Rajesh Kumar,Tennille S Leak,Elad Ziv,Melissa Garcia,Bernd Meibohm,Myriam Fornage,Stephen B Kritchevsky,L Keoki Williams,Kiang Liu,Joshua Galanter,Lewis J Smith,Tamara B Harris,Esteban G Burchard,Christopher R Gignoux,Joseph M Zmuda ,Śaunak Sen

doi:10.1371/journal.pone.0039541

Abstract

BackgroundSmoking tobacco reduces lung function. African Americans have both lower lung function and decreased metabolism of tobacco smoke compared to European Americans. African ancestry is also associated with lower pulmonary function in African Americans. We aimed to determine whether African ancestry modifies the association between smoking and lung function and its rate of decline in African Americans.Methodology/Principal FindingsWe evaluated a prospective ongoing cohort of 1,281 African Americans participating in the Health, Aging, and Body Composition (Health ABC) Study initiated in 1997. We also examined an ongoing prospective cohort initiated in 1985 of 1,223 African Americans in the Coronary Artery Disease in Young Adults (CARDIA) Study. Pulmonary function and tobacco smoking exposure were measured at baseline and repeatedly over the follow-up period. Individual genetic ancestry proportions were estimated using ancestry informative markers selected to distinguish European and West African ancestry. African Americans with a high proportion of African ancestry had lower baseline forced expiratory volume in one second (FEV1) per pack-year of smoking (−5.7 ml FEV1/ smoking pack-year) compared with smokers with lower African ancestry (−4.6 ml in FEV1/ smoking pack-year) (interaction P value = 0.17). Longitudinal analyses revealed a suggestive interaction between smoking, and African ancestry on the rate of FEV1 decline in Health ABC and independently replicated in CARDIA.Conclusions/SignificanceAfrican American individuals with a high proportion of African ancestry are at greater risk for losing lung function while smoking.

Highlights

Tobacco smoking is the leading cause of preventable deaths in the United States and is an important contributor to accelerated lung function decline [1]
Using two independent adult cohorts, we demonstrated that smoking has a greater impact on reduced lung function among African Americans with high African ancestry than those with low African ancestry
Inclusion of the 1,332 AIMs separately in models examining the association between tobacco smoke exposure and baseline FEV1 did not abrogate the response, even after correcting for multiple testing using false discovery rate [34], suggesting none of the ancestry informative markers were responsible for the observed associations

Summary

Introduction

Tobacco smoking is the leading cause of preventable deaths in the United States and is an important contributor to accelerated lung function decline [1]. African Americans have lower normative lung function when compared with European Americans [5,6] and African ancestry is associated with lower pulmonary function [7]. The extent to which differences in exposure and susceptibility to tobacco smoke impact racial differences in lung function decline is unclear [8,9]. This question may have clinical or public health relevance since African American individuals may be susceptible to smoking related diseases such as chronic obstructive lung disease [8,9,10,11,12].

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