PMID- 35023945
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20240405
IS  - 1178-7031 (Print)
IS  - 1178-7031 (Electronic)
IS  - 1178-7031 (Linking)
VI  - 15
DP  - 2022
TI  - Quantile-Specific Heritability of Inflammatory and Oxidative Stress Biomarkers 
      Linked to Cardiovascular Disease.
PG  - 85-103
LID - 10.2147/JIR.S347402 [doi]
AB  - PURPOSE: Heritability (h(2) , the proportion of the phenotypic variance 
      attributable to additive genetic effects) is traditionally assumed to be constant 
      throughout the distribution of the phenotype. However, the heritabilities of 
      circulating C-reactive protein, interleukin-6, plasminogen activator inhibitor 
      type-1 (PAI-1), and monocyte chemoattractant protein-1 (MCP-1) concentrations 
      depend upon whether the phenotype is high or low relative to their distributions 
      (quantile-dependent expressivity), which may account for apparent 
      gene-environment interactions. Whether the heritabilities of other inflammatory 
      biomarkers linked to cardiovascular disease are quantile-dependent remain to be 
      determined. PATIENTS AND METHODS: Quantile-specific offspring-parent (beta(OP)) and 
      full-sib regression slopes (beta(FS)) were estimated by applying quantile regression 
      to the age- and sex-adjusted phenotypes of families surveyed as part of the 
      Framingham Heart Study. Quantile-specific heritabilities were calculated as: h(2) 
      =2beta(OP)/(1+r(spouse)) and h(2) =(1+8r(spouse)beta(FS))(0.5)-1/(2r(spouse)). 
      RESULTS: Heritability (h(2) +/- SE) of lipoprotein-associated phospholipase A2 
      (Lp-PLA(2)) mass concentrations increased from 0.11 +/- 0.03 at the 10(th) 
      percentile, 0.08 +/- 0.03 at the 25(th), 0.12 +/- 0.03 at the 50(th), 0.20 +/- 0.04 at 
      the 75(th), and 0.26 +/- 0.06 at the 90(th) percentile, or 0.0023 +/- 0.0006 per each 
      one-percent increase in the phenotype distribution (P(linear trend)= 0.0004). 
      Similarly, h(2) increased 0.0029 +/- 0.0011 (P(linear trend)= 0.01) for 
      sP-selectin, 0.0032 +/- 0.0009 (P(linear trend)= 0.0001) for soluble intercellular 
      adhesion molecule 1 (sICAM-1), and 0.0026 +/- 0.0006 for tumor necrosis factor 
      receptor 2 (TNFR2) (P(linear trend)= 5.0 x 10(-6)) per each one-percent increase 
      in their distributions when estimated from beta(OP). Osteoprotegerin and soluble ST2 
      heritability also increased significantly with increasing percentiles of their 
      distributions when estimated from beta(FS). Lp-PLA(2) activity, CD40 ligand, TNFalpha, 
      interleukin-18, and myeloperoxidase heritability showed no significant 
      quantile-dependence. CONCLUSION: The heritabilities of circulating 
      Lp-PLA(2)-mass, sP-selectin, sICAM-1, TNFR2, osteoprotegerin and soluble ST2 
      concentrations are quantile-dependent, which may contribute to purported genetic 
      modulations of: 1) sP-selectin's relationships to venous thrombosis, pulmonary 
      hypertension, type 2 diabetes and atorvastatin treatment; 2) sICAM-I's 
      relationships to brain abscess and atorvastatin treatment; and 3) Lp-PLA(2)'s 
      relationships to myocardial infarction and preeclampsia.
CI  - (c) 2022 Williams.
FAU - Williams, Paul T
AU  - Williams PT
AD  - Molecular Biophysics & Integrated Bioimaging Division, Lawrence Berkeley National 
      Laboratory, Berkeley, CA, USA.
LA  - eng
PT  - Journal Article
DEP - 20220105
PL  - New Zealand
TA  - J Inflamm Res
JT  - Journal of inflammation research
JID - 101512684
PMC - PMC8743501
OTO - NOTNLM
OT  - P-selectin
OT  - gene-environment interaction: heritability
OT  - intercellular adhesion molecule-1
OT  - lipoprotein-associated phospholipase A2
OT  - osteoprotegerin
COIS- This research was supported by NIH grant R21ES020700 from the National Institute 
      of Environmental Health Sciences, and an unrestricted gift from HOKA ONE ONE. 
      There are no conflicts of interest to disclose.
EDAT- 2022/01/14 06:00
MHDA- 2022/01/14 06:01
PMCR- 2022/01/05
CRDT- 2022/01/13 12:26
PHST- 2021/11/02 00:00 [received]
PHST- 2021/12/16 00:00 [accepted]
PHST- 2022/01/13 12:26 [entrez]
PHST- 2022/01/14 06:00 [pubmed]
PHST- 2022/01/14 06:01 [medline]
PHST- 2022/01/05 00:00 [pmc-release]
AID - 347402 [pii]
AID - 10.2147/JIR.S347402 [doi]
PST - epublish
SO  - J Inflamm Res. 2022 Jan 5;15:85-103. doi: 10.2147/JIR.S347402. eCollection 2022.