Evidence for major genes influencing pulmonary function in the NHLBI Family Heart Study

Jemma B. Wilk, Luc Djousse, Donna K. Arnett, Stephen S. Rich, Michael A. Province, Steven Hunt, Robert O. Crapo, Millicent Higgins, Richard H. Myers

Research output: Contribution to journalArticle

81 Citations (Scopus)

Abstract

Segregation analysis was performed on the pulmonary measures forced expiratory volume in one second (FEV1), forced vital capacity (FVC), and the ratio of FEV1/FVC in 455 randomly ascertained families from the NHLBI Family Heart Study (FHS). Gender specific standardized residuals were used as the phenotypic variable in both familial correlation and segregation analyses. These residuals represented adjustments for the effects of age, age2, age3, Body Mass Index (BMI, kg/m2), height, the ratio of waist to hip measurements (WHR), the presence of coronary heart disease, smoking history, and pack years for current smokers. Sibling correlations were not different from parent-offspring correlations for all three traits, and heritability estimates for FEV1, FVC, and the FEV1/FVC ratio were 0.515, 0.540, and 0.449, respectively. Segregation analysis of FEV1, a trait that measures airflow, indicated that a dominant major gene best fits the data, although a residual familial correlation supports the presence of an additional polygenic or common environmental component. For FVC, a trait that measures lung volume, alternative models could not be statistically differentiated, but the transmission probabilities do not support a Mendelian major gene. The best model for FEV1/FVC ratio is a non-Mendelian codominant model, perhaps due to the mixing of the individual underlying distributions influencing airflow and lung volume. These results support the hypothesis that complex relationships exist for lung function traits and that multiple genes and environmental factors influence lung function. (C) 2000 Wiley-Liss, Inc.

Original languageEnglish
Pages (from-to)81-94
Number of pages14
JournalGenetic Epidemiology
Volume19
Issue number1
DOIs
Publication statusPublished - Jul 2000
Externally publishedYes

Fingerprint

National Heart, Lung, and Blood Institute (U.S.)
Vital Capacity
Lung
Genes
Dominant Genes
Waist-Hip Ratio
Forced Expiratory Volume
Coronary Disease
Body Mass Index
Smoking
History

Keywords

  • FEV1
  • FEV1/FVC ratio
  • FVC
  • Segregation analysis

ASJC Scopus subject areas

  • Genetics(clinical)
  • Epidemiology

Cite this

Evidence for major genes influencing pulmonary function in the NHLBI Family Heart Study. / Wilk, Jemma B.; Djousse, Luc; Arnett, Donna K.; Rich, Stephen S.; Province, Michael A.; Hunt, Steven; Crapo, Robert O.; Higgins, Millicent; Myers, Richard H.

In: Genetic Epidemiology, Vol. 19, No. 1, 07.2000, p. 81-94.

Research output: Contribution to journalArticle

Wilk, JB, Djousse, L, Arnett, DK, Rich, SS, Province, MA, Hunt, S, Crapo, RO, Higgins, M & Myers, RH 2000, 'Evidence for major genes influencing pulmonary function in the NHLBI Family Heart Study', Genetic Epidemiology, vol. 19, no. 1, pp. 81-94. https://doi.org/10.1002/1098-2272(200007)19:1<81::AID-GEPI6>3.0.CO;2-8
Wilk, Jemma B. ; Djousse, Luc ; Arnett, Donna K. ; Rich, Stephen S. ; Province, Michael A. ; Hunt, Steven ; Crapo, Robert O. ; Higgins, Millicent ; Myers, Richard H. / Evidence for major genes influencing pulmonary function in the NHLBI Family Heart Study. In: Genetic Epidemiology. 2000 ; Vol. 19, No. 1. pp. 81-94.
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