Major genetic effect on forced vital capacity: The Humboldt family study

Chen, Yue; Rennie, Donna; Lockinger, Lori A.; Dosman, James A.

doi:10.1002/(sici)1098-2272(1997)14:1<63::aid-gepi5>3.0.co;2-6

Cited by 12 publications

(5 citation statements)

References 16 publications

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“…Offspring-parent and sibling regression coefficients are simple estimates of heritability relative to its estimation from twin studies, family studies and segregation analyses. As has been reported previously in this and other cohorts (Devor & Crawford, 1984;Coultas et al, 1991;Klimentidis et al, 2013;Redline et al, 1989;Wilk et al, 2000;Tarnoki et al, 2013;Hukkinen et al, 2011;Hallberg et al, 2010;DeMeo et al, 2004;McClearn et al, 1994;Palmer et al, 2001;Astemborski, Beaty & Cohen, 1985;Beaty et al, 1987;Lewitter et al, 1984;Cotch, Beaty & Cohen, 1990;Chen et al, 1996;Chen et al, 1997;Givelber et al, 1998;Ingebrigtsen et al, 2011;Joost et al, 2002;Tian et al, 2017;Yamada et al, 2015), these analyses showed moderate to strong heritabilities for pulmonary function. The generally greater heritabilities for the sib-based vs. offspring-parent-based estimates have been reported by others (Givelber et al, 1998) and suggest that shared environment or dominance effects might not be negligible.…”

Section: Methodological Issuessupporting

confidence: 88%

“…Heritability estimates range widely across family and twins studies, from 0.09 to 0.68 for FEV 1 (mean 0.39), 0.20 to 0.78 for FVC (mean 0.45), and 0.16 to 0.64 for the FEV 1 /FVC ratio (mean 0.36) (Devor & Crawford, 1984;Coultas et al, 1991;Klimentidis et al, 2013;Redline et al, 1989;Wilk et al, 2000;Tarnoki et al, 2013;Hukkinen et al, 2011;Hallberg et al, 2010;DeMeo et al, 2004;McClearn et al, 1994;Palmer et al, 2001;Astemborski, Beaty & Cohen, 1985;Beaty et al, 1987;Lewitter et al, 1984;Cotch, Beaty & Cohen, 1990;Chen et al, 1996;Chen et al, 1997;Givelber et al, 1998;Ingebrigtsen et al, 2011;Joost et al, 2002;Tian et al, 2017;Yamada et al, 2015). Prior segregation analyses of pulmonary function generally favor its polygenic inheritance (Chen et al, 1996;Chen et al, 1997;Givelber et al, 1998). Forty-nine genetic loci have been significantly related to pulmonary function in meta-analyses of 38,199 individuals of European ancestry from 17 genome-wide association studies (GWAS) (Loth et al, 2014;Soler Artigas et al, 2015;Hancock et al, 2010;Repapi et al, 2010;Soler Artigas et al, 2011).…”

Section: Introductionmentioning

confidence: 99%

“…It is not known whether quantilespecific genetic effects apply to pulmonary function. The aforementioned twin and family studies (Devor & Crawford, 1984;Coultas et al, 1991;Klimentidis et al, 2013;Redline et al, 1989;Wilk et al, 2000;Tarnoki et al, 2013;Hukkinen et al, 2011;Hallberg et al, 2010;DeMeo et al, 2004;McClearn et al, 1994;Palmer et al, 2001;Astemborski, Beaty & Cohen, 1985;Beaty et al, 1987;Lewitter et al, 1984;Cotch, Beaty & Cohen, 1990;Chen et al, 1996;Chen et al, 1997;Givelber et al, 1998;Ingebrigtsen et al, 2011;Joost et al, 2002;Tian et al, 2017;Yamada et al, 2015), segregation analyses (Chen et al, 1996;Chen et al, 1997;Givelber et al, 1998), and GWAS (Loth et al, 2014;Soler Artigas et al, 2015;Hancock et al, 2010;Repapi et al, 2010;Soler Artigas et al, 2011) are all based on the assumption that the genetic and other inherited effects are the same throughout the distributions of pulmonary function, i.e., the same whether pulmonary function is high or low relative to the population distribution. Quantile regression was therefore applied to spirometric data from the Framingham Study (Dawber, Meadors & Moore, 1951;Kannel et al, 1979;Splansky et al, 2007) to assess whether quantile-dependent expressivity affects its heritability.…”

Section: Introductionmentioning

confidence: 99%

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Spirometric traits show quantile-dependent heritability, which may contribute to their gene-environment interactions with smoking and pollution

Williams

2020

PeerJ

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Background “Quantile-dependent expressivity” refers to a genetic effect that is dependent upon whether the phenotype (e.g., spirometric data) is high or low relative to its population distribution. Forced vital capacity (FVC), forced expiratory volume in 1 second (FEV1), and the FEV1/FVC ratio are moderately heritable spirometric traits. The aim of the analyses is to test whether their heritability (h2) is constant over all quantiles of their distribution. Methods Quantile regression was applied to the mean age, sex, height and smoking-adjusted spirometric data over multiple visits in 9,993 offspring-parent pairs and 1,930 sibships from the Framingham Heart Study to obtain robust estimates of offspring-parent (βOP), offspring-midparent (βOM), and full-sib regression slopes (βFS). Nonparametric significance levels were obtained from 1,000 bootstrap samples. βOPs were used as simple indicators of quantile-specific heritability (i.e., h2 = 2βOP/(1+rspouse), where rspouse was the correlation between spouses). Results βOP ± standard error (SE) decreased by 0.0009 ± 0.0003 (P = 0.003) with every one-percent increment in the population distribution of FEV1/FVC, i.e., βOP ± SE were: 0.182 ± 0.031, 0.152 ± 0.015; 0.136 ± 0.011; 0.121 ± 0.013; and 0.099 ± 0.013 at the 10th, 25th, 50th, 75th, and 90th percentiles of the FEV1/FVC distribution, respectively. These correspond to h2 ± SEs of 0.350 ± 0.060 at the 10th, 0.292 ± 0.029 at the 25th, 0.262 ± 0.020 at the 50th, 0.234 ± 0.025 at the 75th, and 0.191 ± 0.025 at the 90th percentiles of the FEV1/FVC ratio. Maximum mid-expiratory flow (MMEF) h2 ± SEs increased 0.0025 ± 0.0007 (P = 0.0004) with every one-percent increment in its distribution, i.e.: 0.467 ± 0.046, 0.467 ± 0.033, 0.554 ± 0.038, 0.615 ± 0.042, and 0.675 ± 0.060 at the 10th, 25th, 50th, 75th, and 90th percentiles of its distribution. This was due to forced expiratory flow at 75% of FVC (FEF75%), whose quantile-specific h2 increased an average of 0.0042 ± 0.0008 for every one-percent increment in its distribution. It is speculated that previously reported gene-environment interactions may be partially attributable to quantile-specific h2, i.e., greater heritability in individuals with lower FEV1/FVC due to smoking or airborne particles exposure vs. nonsmoking, unexposed individuals. Conclusion Heritabilities of FEV1/FVC, MMEF, and FEF75% from quantile-regression of offspring-parent and sibling spirometric data suggest their quantile-dependent expressivity.

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Section: Methodological Issuessupporting

confidence: 88%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Spirometric traits show quantile-dependent heritability, which may contribute to their gene-environment interactions with smoking and pollution

Williams

2020

PeerJ

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“…FEV1 is a measure of flow and is highly influenced by airway obstruction, while FVC is an index of lung volume. FEV1 is only modestly correlated with FVC, suggesting interindividual differences in airway size relative to lung volume [Chen et al, 1997]. Thus, the ratio of FEV1 to FVC is used as a third measure of pulmonary function and considered an index of obstructive pulmonary disease [Rybicki et al, 1990].…”

Section: Introductionmentioning

confidence: 99%

“…In a segregation analysis of the Framingham cohort, FEV1 was not found to be associated with a major gene, but large polygenic influences were supported [Givelber et al, 1998]. The Humboldt Family Study performed a segregation analysis of FVC and found evidence of a major gene, but environmental factors remained significant in a portion of the families [Chen et al, 1997].…”

Section: Introductionmentioning

confidence: 99%