Related Experiment Video

Updated: Aug 12, 2025

Generation of a Chronic Obstructive Pulmonary Disease Model in Mice by Repeated Ozone Exposure

Generation of a Chronic Obstructive Pulmonary Disease Model in Mice by Repeated Ozone Exposure

Published on: August 25, 2017

X chromosome associations with chronic obstructive pulmonary disease and related phenotypes: an X chromosome-wide

Lystra P Hayden^1,2, Brian D Hobbs^2,3, Robert Busch⁴

¹Division of Pulmonary Medicine, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA.

Respiratory Research

|February 2, 2023

Abstract

Background:

The association between genetic variants on the X chromosome to risk of COPD has not been fully explored. We hypothesize that the X chromosome harbors variants important in determining risk of COPD related phenotypes and may drive sex differences in COPD manifestations.

Methods:

Using X chromosome data from three COPD-enriched cohorts of adult smokers, we performed X chromosome specific quality control, imputation, and testing for association with COPD case-control status, lung function, and quantitative emphysema. Analyses were performed among all subjects, then stratified by sex, and subsequently combined in meta-analyses.

Results:

Among 10,193 subjects of non-Hispanic white or European ancestry, a variant near TMSB4X, rs5979771, reached genome-wide significance for association with lung function measured by FEV₁/FVC ([Formula: see text] 0.020, SE 0.004, p 4.97 × 10^-08), with suggestive evidence of association with FEV₁ ([Formula: see text] 0.092, SE 0.018, p 3.40 × 10^-07). Sex-stratified analyses revealed X chromosome variants that were differentially trending in one sex, with significantly different effect sizes or directions.

Conclusions:

This investigation identified loci influencing lung function, COPD, and emphysema in a comprehensive genetic association meta-analysis of X chromosome genetic markers from multiple COPD-related datasets. Sex differences play an important role in the pathobiology of complex lung disease, including X chromosome variants that demonstrate differential effects by sex and variants that may be relevant through escape from X chromosome inactivation. Comprehensive interrogation of the X chromosome to better understand genetic control of COPD and lung function is important to further understanding of disease pathology. Trial registration Genetic Epidemiology of COPD Study (COPDGene) is registered at ClinicalTrials.gov, NCT00608764 (Active since January 28, 2008). Evaluation of COPD Longitudinally to Identify Predictive Surrogate Endpoints Study (ECLIPSE), GlaxoSmithKline study code SCO104960, is registered at ClinicalTrials.gov, NCT00292552 (Active since February 16, 2006). Genetics of COPD in Norway Study (GenKOLS) holds GlaxoSmithKline study code RES11080, Genetics of Chronic Obstructive Lung Disease.

Keywords:

COPD Emphysema Lung function Sex differences X chromosome inactivation X chromosome-wide association study

More Related Videos

Generation of High Quality Chromatin Immunoprecipitation DNA Template for High-throughput Sequencing ChIP-seq

Generation of High Quality Chromatin Immunoprecipitation DNA Template for High-throughput Sequencing ChIP-seq

Published on: April 19, 2013

Phenotyping Mouse Pulmonary Function In Vivo with the Lung Diffusing Capacity

Phenotyping Mouse Pulmonary Function In Vivo with the Lung Diffusing Capacity

Published on: January 6, 2015

Related Concept Videos

Chronic Obstructive Pulmonary Disease-I: Introduction

Chronic Obstructive Pulmonary Disease-I: Introduction

Chronic Obstructive Pulmonary Disease (COPD) is a long-lasting respiratory condition requiring continuous attention and care. It is a progressive lung disease that leads to breathing challenges due to airflow obstruction. It manifests as persistent respiratory symptoms and restricted airflow resulting from abnormalities in the airways and alveoli, usually due to long-term exposure to harmful particles or gases. COPD mainly consists of two primary conditions: emphysema and chronic bronchitis.

Chronic Obstructive Pulmonary Disease-II: Pathophysiology

Chronic Obstructive Pulmonary Disease-II: Pathophysiology

Chronic Obstructive Pulmonary Disease (COPD) pathophysiology is intricate and multifaceted, involving a complex interplay of physiological processes. Understanding these mechanisms is crucial for effectively managing and treating COPD. Here is an in-depth look at the critical elements in the pathophysiology of COPD:
Chronic Inflammation

Chronic Obstructive Pulmonary Disease

Chronic Obstructive Pulmonary Disease

COPD is defined as a heterogeneous lung condition marked by persistent respiratory symptoms such as dyspnea, cough, and sputum production, caused by abnormalities in the airways that cause airflow obstruction.
Smoking is a primary risk factor for COPD, with over 80% of patients having a history of it. Patients typically experience progressive dyspnea or labored breathing, frequent coughing, and recurrent pulmonary infections. Many eventually succumb to respiratory failure, characterized by...

Cystic Fibrosis: Pathogenesis

Cystic Fibrosis: Pathogenesis

Cystic fibrosis (CF), an autosomal recessive disorder, significantly affects the function of exocrine glands. This genetically inherited disease is characterized by the production of thick and sticky mucus, which can severely affect various organs and systems in the body.
CF is primarily caused by a genetic mutation in a chromosome 7 gene coding for the cystic fibrosis transmembrane conductance regulator (CFTR) protein. The most common gene mutation leading to CF is the ΔF508 mutation,...

X-linked Traits

X-linked Traits

In most mammalian species, females have two X sex chromosomes and males have an X and Y. As a result, mutations on the X chromosome in females may be masked by the presence of a normal allele on the second X. In contrast, a mutation on the X chromosome in males more often causes observable biological defects, as there is no normal X to compensate. Trait variations arising from mutations on the X chromosome are called “X-linked”.

Chronic Obstructive Pulmonary Disease-III: Symptoms and Complications.

Chronic Obstructive Pulmonary Disease-III: Symptoms and Complications.

Understanding the variety of primary symptoms and systemic complications that characterize chronic obstructive pulmonary disease (COPD) is crucial for healthcare professionals.
Symptoms of COPD can be classified as primary or systemic. Primary symptoms relate to reduced airflow, while systemic or extrapulmonary symptoms relate to COPD's broader impact on the body.
Primary Symptoms of COPD:

Articles linked to this work by shared authors, journal, and citation graph.

Deploying a JupyterHub Server for Academic Research Using Netbooks as an Example.

Current protocols·2026

Gene regulatory network analysis identifies dysregulation of hypoxia pathways as contributing to glioblastoma treatment resistance in females.

Biology of sex differences·2026

Sex differences in gene regulation and its impact on cancer incidence.

iScience·2026

Body Mass Index-related genetic factors and COPD imaging phenotypes.

Annals of the American Thoracic Society·2026

Integrative multi-omic analyses identify major axes of heterogeneity in chronic obstructive pulmonary disease and uncover their molecular contributors.

medRxiv : the preprint server for health sciences·2026

Gene regulatory network analysis identifies dysregulation of hypoxia pathways as contributing to glioblastoma multiforme treatment resistance in females.

medRxiv : the preprint server for health sciences·2026

See all related articles