Heritability of chronic obstructive pulmonary disease and related phenotypes in smokers

Jin Zhou, Michael H. Cho, Peter J. Castaldi, Craig P. Hersh, Edwin K. Silverman, Nan M. Laird

Research output: Contribution to journalArticle

48 Citations (Scopus)

Abstract

Rationale: Previous studies of chronic obstructive pulmonary disease (COPD) have suggested that genetic factors play an important role in the development of disease. However, single-nucleotide polymorphisms that are associated with COPD in genome-wide association studies have been shown to account for only a small percentage of the genetic variance in phenotypes of COPD, such as spirometry and imaging variables. These phenotypes are highly predictive of disease, and family studies have shown that spirometric phenotypes are heritable. Objectives: To assess the heritability and coheritability of four major COPD-related phenotypes (measurements of FEV1, FEV 1/FVC, percent emphysema, and percent gas trapping), and COPD affection status in smokers of non-Hispanic white and African American descent using a population design. Methods: Single-nucleotide polymorphisms from genome-wide association studies chips were used to calculate the relatedness of pairs of individuals and a mixed model was adopted to estimate genetic variance and covariance. Measurements and Main Results: In the non-Hispanic whites, estimated heritabilities of FEV1 and FEV1/FVC were both about 37%, consistent with estimates in the literature from family-based studies. For chest computed tomography scan phenotypes, estimated heritabilitieswerebothclose to25%.Heritability ofCOPDaffection status was estimated as 37.7% in both populations. Conclusions: This study suggests that a large portion of the genetic risk ofCOPDis yet to be discovered and gives rationale for additional genetic studies of COPD. The estimates of coheritability (genetic covariance) for pairs of the phenotypes suggest considerable overlap of causal genetic loci.

Original languageEnglish (US)
Pages (from-to)941-947
Number of pages7
JournalAmerican Journal of Respiratory and Critical Care Medicine
Volume188
Issue number8
DOIs
StatePublished - Oct 15 2013
Externally publishedYes

Fingerprint

Chronic Obstructive Pulmonary Disease
Phenotype
Genome-Wide Association Study
Single Nucleotide Polymorphism
Genetic Loci
Spirometry
Emphysema
African Americans
Population
Thorax
Gases
Tomography

Keywords

  • Chromosomal partition
  • Imaging phenotypes
  • Missing heritability
  • Pleiotropy
  • Pulmonary function

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine
  • Critical Care and Intensive Care Medicine

Cite this

Heritability of chronic obstructive pulmonary disease and related phenotypes in smokers. / Zhou, Jin; Cho, Michael H.; Castaldi, Peter J.; Hersh, Craig P.; Silverman, Edwin K.; Laird, Nan M.

In: American Journal of Respiratory and Critical Care Medicine, Vol. 188, No. 8, 15.10.2013, p. 941-947.

Research output: Contribution to journalArticle

Zhou, Jin ; Cho, Michael H. ; Castaldi, Peter J. ; Hersh, Craig P. ; Silverman, Edwin K. ; Laird, Nan M. / Heritability of chronic obstructive pulmonary disease and related phenotypes in smokers. In: American Journal of Respiratory and Critical Care Medicine. 2013 ; Vol. 188, No. 8. pp. 941-947.
@article{5a1e0e77dac94b86a108d5cbaa34c908,
title = "Heritability of chronic obstructive pulmonary disease and related phenotypes in smokers",
abstract = "Rationale: Previous studies of chronic obstructive pulmonary disease (COPD) have suggested that genetic factors play an important role in the development of disease. However, single-nucleotide polymorphisms that are associated with COPD in genome-wide association studies have been shown to account for only a small percentage of the genetic variance in phenotypes of COPD, such as spirometry and imaging variables. These phenotypes are highly predictive of disease, and family studies have shown that spirometric phenotypes are heritable. Objectives: To assess the heritability and coheritability of four major COPD-related phenotypes (measurements of FEV1, FEV 1/FVC, percent emphysema, and percent gas trapping), and COPD affection status in smokers of non-Hispanic white and African American descent using a population design. Methods: Single-nucleotide polymorphisms from genome-wide association studies chips were used to calculate the relatedness of pairs of individuals and a mixed model was adopted to estimate genetic variance and covariance. Measurements and Main Results: In the non-Hispanic whites, estimated heritabilities of FEV1 and FEV1/FVC were both about 37{\%}, consistent with estimates in the literature from family-based studies. For chest computed tomography scan phenotypes, estimated heritabilitieswerebothclose to25{\%}.Heritability ofCOPDaffection status was estimated as 37.7{\%} in both populations. Conclusions: This study suggests that a large portion of the genetic risk ofCOPDis yet to be discovered and gives rationale for additional genetic studies of COPD. The estimates of coheritability (genetic covariance) for pairs of the phenotypes suggest considerable overlap of causal genetic loci.",
keywords = "Chromosomal partition, Imaging phenotypes, Missing heritability, Pleiotropy, Pulmonary function",
author = "Jin Zhou and Cho, {Michael H.} and Castaldi, {Peter J.} and Hersh, {Craig P.} and Silverman, {Edwin K.} and Laird, {Nan M.}",
year = "2013",
month = "10",
day = "15",
doi = "10.1164/rccm.201302-0263OC",
language = "English (US)",
volume = "188",
pages = "941--947",
journal = "American Journal of Respiratory and Critical Care Medicine",
issn = "1073-449X",
publisher = "American Thoracic Society",
number = "8",

}

TY - JOUR

T1 - Heritability of chronic obstructive pulmonary disease and related phenotypes in smokers

AU - Zhou, Jin

AU - Cho, Michael H.

AU - Castaldi, Peter J.

AU - Hersh, Craig P.

AU - Silverman, Edwin K.

AU - Laird, Nan M.

PY - 2013/10/15

Y1 - 2013/10/15

N2 - Rationale: Previous studies of chronic obstructive pulmonary disease (COPD) have suggested that genetic factors play an important role in the development of disease. However, single-nucleotide polymorphisms that are associated with COPD in genome-wide association studies have been shown to account for only a small percentage of the genetic variance in phenotypes of COPD, such as spirometry and imaging variables. These phenotypes are highly predictive of disease, and family studies have shown that spirometric phenotypes are heritable. Objectives: To assess the heritability and coheritability of four major COPD-related phenotypes (measurements of FEV1, FEV 1/FVC, percent emphysema, and percent gas trapping), and COPD affection status in smokers of non-Hispanic white and African American descent using a population design. Methods: Single-nucleotide polymorphisms from genome-wide association studies chips were used to calculate the relatedness of pairs of individuals and a mixed model was adopted to estimate genetic variance and covariance. Measurements and Main Results: In the non-Hispanic whites, estimated heritabilities of FEV1 and FEV1/FVC were both about 37%, consistent with estimates in the literature from family-based studies. For chest computed tomography scan phenotypes, estimated heritabilitieswerebothclose to25%.Heritability ofCOPDaffection status was estimated as 37.7% in both populations. Conclusions: This study suggests that a large portion of the genetic risk ofCOPDis yet to be discovered and gives rationale for additional genetic studies of COPD. The estimates of coheritability (genetic covariance) for pairs of the phenotypes suggest considerable overlap of causal genetic loci.

AB - Rationale: Previous studies of chronic obstructive pulmonary disease (COPD) have suggested that genetic factors play an important role in the development of disease. However, single-nucleotide polymorphisms that are associated with COPD in genome-wide association studies have been shown to account for only a small percentage of the genetic variance in phenotypes of COPD, such as spirometry and imaging variables. These phenotypes are highly predictive of disease, and family studies have shown that spirometric phenotypes are heritable. Objectives: To assess the heritability and coheritability of four major COPD-related phenotypes (measurements of FEV1, FEV 1/FVC, percent emphysema, and percent gas trapping), and COPD affection status in smokers of non-Hispanic white and African American descent using a population design. Methods: Single-nucleotide polymorphisms from genome-wide association studies chips were used to calculate the relatedness of pairs of individuals and a mixed model was adopted to estimate genetic variance and covariance. Measurements and Main Results: In the non-Hispanic whites, estimated heritabilities of FEV1 and FEV1/FVC were both about 37%, consistent with estimates in the literature from family-based studies. For chest computed tomography scan phenotypes, estimated heritabilitieswerebothclose to25%.Heritability ofCOPDaffection status was estimated as 37.7% in both populations. Conclusions: This study suggests that a large portion of the genetic risk ofCOPDis yet to be discovered and gives rationale for additional genetic studies of COPD. The estimates of coheritability (genetic covariance) for pairs of the phenotypes suggest considerable overlap of causal genetic loci.

KW - Chromosomal partition

KW - Imaging phenotypes

KW - Missing heritability

KW - Pleiotropy

KW - Pulmonary function

UR - http://www.scopus.com/inward/record.url?scp=84886403801&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84886403801&partnerID=8YFLogxK

U2 - 10.1164/rccm.201302-0263OC

DO - 10.1164/rccm.201302-0263OC

M3 - Article

VL - 188

SP - 941

EP - 947

JO - American Journal of Respiratory and Critical Care Medicine

JF - American Journal of Respiratory and Critical Care Medicine

SN - 1073-449X

IS - 8

ER -