Quantile-dependent expressivity of serum C-reactive protein concentrations in family sets
Abstract
“Quantile-dependent expressivity” occurs when the effect size of a genetic variant depends upon whether the phenotype (e.g., C-reactive protein, CRP) is high or low relative to its distribution. We have previously shown that the heritabilities (h2) of coffee and alcohol consumption, postprandial lipemia, lipoproteins, leptin, adiponectin, adiposity, and pulmonary function are quantile-specific. Whether CRP heritability is quantile-specific is currently unknown. MethodsSerum CRP concentrations from 2,036 sibships and 6,144 offspring-parent pairs were analyzed from the Framingham Heart Study. Quantile-specific heritability from full-sib (βFS,h2={(1 + 8rspouseβFS)0.5- 1}/(2rspouse)) and offspring-parent regression slopes (βOP,h2= 2βOP/(1 + rspouse)) were estimated robustly by quantile regression with nonparametric significance determined from 1,000 bootstrap samples. ResultsQuantile-specifich2(±SE) increased with increasing percentiles of the offspring’s age- and sex-adjusted CRP distribution when estimated from βOP(Ptrend= 0.0004): 0.02 ± 0.01 at the 10th, 0.04 ± 0.01 at the 25th, 0.10 ± 0.02 at the 50th, 0.20 ± 0.05 at the 75th, and 0.33 ± 0.10 at the 90th percentile, and when estimated from βFS(Ptrend= 0.0008): 0.03±0.01 at the 10th, 0.06 ± 0.02 at the 25th, 0.14 ± 0.03 at the 50th, 0.24 ± 0.05 at the 75th, and 0.53 ± 0.21 at the 90th percentile. ConclusionHeritability of serum CRP concentration is quantile-specific,more »
- Authors:
-
[1]
- Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States). Molecular Biophysics & Integrated Bioimaging Division
- Publication Date:
- Research Org.:
- Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States)
- Sponsoring Org.:
- USDOE Office of Science (SC)
- OSTI Identifier:
- 1815952
- Grant/Contract Number:
- AC02-05CH11231
- Resource Type:
- Accepted Manuscript
- Journal Name:
- PeerJ
- Additional Journal Information:
- Journal Volume: 9; Journal ID: ISSN 2167-8359
- Publisher:
- PeerJ Inc.
- Country of Publication:
- United States
- Language:
- English
- Subject:
- 59 BASIC BIOLOGICAL SCIENCES
Citation Formats
Williams, Paul T. Quantile-dependent expressivity of serum C-reactive protein concentrations in family sets. United States: N. p., 2021.
Web. doi:10.7717/peerj.10914.
Williams, Paul T. Quantile-dependent expressivity of serum C-reactive protein concentrations in family sets. United States. https://doi.org/10.7717/peerj.10914
Williams, Paul T. Tue .
"Quantile-dependent expressivity of serum C-reactive protein concentrations in family sets". United States. https://doi.org/10.7717/peerj.10914. https://www.osti.gov/servlets/purl/1815952.
@article{osti_1815952,
title = {Quantile-dependent expressivity of serum C-reactive protein concentrations in family sets},
author = {Williams, Paul T.},
abstractNote = {“Quantile-dependent expressivity” occurs when the effect size of a genetic variant depends upon whether the phenotype (e.g., C-reactive protein, CRP) is high or low relative to its distribution. We have previously shown that the heritabilities (h2) of coffee and alcohol consumption, postprandial lipemia, lipoproteins, leptin, adiponectin, adiposity, and pulmonary function are quantile-specific. Whether CRP heritability is quantile-specific is currently unknown. MethodsSerum CRP concentrations from 2,036 sibships and 6,144 offspring-parent pairs were analyzed from the Framingham Heart Study. Quantile-specific heritability from full-sib (βFS,h2={(1 + 8rspouseβFS)0.5- 1}/(2rspouse)) and offspring-parent regression slopes (βOP,h2= 2βOP/(1 + rspouse)) were estimated robustly by quantile regression with nonparametric significance determined from 1,000 bootstrap samples. ResultsQuantile-specifich2(±SE) increased with increasing percentiles of the offspring’s age- and sex-adjusted CRP distribution when estimated from βOP(Ptrend= 0.0004): 0.02 ± 0.01 at the 10th, 0.04 ± 0.01 at the 25th, 0.10 ± 0.02 at the 50th, 0.20 ± 0.05 at the 75th, and 0.33 ± 0.10 at the 90th percentile, and when estimated from βFS(Ptrend= 0.0008): 0.03±0.01 at the 10th, 0.06 ± 0.02 at the 25th, 0.14 ± 0.03 at the 50th, 0.24 ± 0.05 at the 75th, and 0.53 ± 0.21 at the 90th percentile. ConclusionHeritability of serum CRP concentration is quantile-specific, which may explain or contribute to the inflated CRP differences betweenCRP(rs1130864, rs1205, rs1800947, rs2794521, rs3091244),FGB(rs1800787),IL-6(rs1800795, rs1800796),IL6R(rs8192284),TNF-α (rs1800629) andAPOEgenotypes following CABG surgery, stroke, TIA, curative esophagectomy, intensive periodontal therapy, or acute exercise; during acute coronary syndrome orStaphylococcus aureusbacteremia; or in patients with chronic rheumatoid arthritis, diabetes, peripheral arterial disease, ankylosing spondylitis, obesity or inflammatory bowel disease or who smoke.},
doi = {10.7717/peerj.10914},
journal = {PeerJ},
number = ,
volume = 9,
place = {United States},
year = {Tue Feb 16 00:00:00 EST 2021},
month = {Tue Feb 16 00:00:00 EST 2021}
}
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