Quantile-Specific Heritability of Mean Platelet Volume, Leukocyte Count, and Other Blood Cell Phenotypes.

IF 2 4区医学 Q3 GENETICS & HEREDITY

Lifestyle Genomics Pub Date : 2022-01-01 DOI:10.1159/000527048

Paul T Williams

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引用次数: 1

Abstract

Introduction: "Quantile-dependent expressivity" occurs when the effect size of a genetic variant depends upon whether the phenotype (e.g., mean platelet volume, MPV) is high or low relative to its distribution.

Methods: Offspring-parent regression slopes (βOP) were estimated by quantile regression, from which quantile-specific heritabilities (h2) were calculated (h2 = 2βOP/[1 + rspouse]) for blood cell phenotypes in 3,929 parent-offspring pairs from the Framingham Heart Study.

Results: Quantile-specific h2 (±SE) increased with increasing percentiles of the offspring's age- and sex-adjusted MPV distribution (plinear = 0.0001): 0.48 ± 0.09 at the 10th, 0.53 ± 0.04 at the 25th, 0.70 ± 0.06 at the 50th, 0.74 ± 0.06 at the 75th, and 0.90 ± 0.12 at the 90th percentile. Quantile-specific h2 also increased with increasing percentiles of the offspring's white blood cell (WBC, plinear = 0.002), monocyte (plinear = 0.01), and eosinophil distributions (plinear = 0.0005). In contrast, heritibilities of red blood cell (RBC) count, hematocrit (HCT), and hemoglobin (HGB) showed little evidence of quantile dependence. Quantile-dependent expressivity is consistent with gene-environment interactions reported by others, including (1) greater increases in WBC and PLT concentrations in subjects who are glutathione-S-transferase Mu1 (GSTM1) null homozygotes than GSTM1 sufficient when exposed to endotoxin; (2) significantly higher WBC count in AA homozygotes than carriers of the G-allele of the glutathione S-transferase P1 (GSTP1) rs1695 polymorphism at low but not high benzene exposure in shoe factory workers; (3) higher WBC counts in TT homozygotes than C-allele carriers of the interleukin-1β (IL1B) c.315C>T polymorphism after undergoing surgery for infective endocarditis but not before surgery.

Discussion/conclusion: Quantile-dependent expressivity may explain several purported gene-environment interactions involving blood cell phenotypes.

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平均血小板体积、白细胞计数和其他血细胞表型的分位数特异性遗传性。

当基因变异的效应大小取决于表型(例如，平均血小板体积，MPV)相对于其分布是高还是低时，就会出现“分位数依赖性表达性”。方法:采用分位数回归法估计后代-亲本回归斜率(βOP)，并计算来自Framingham心脏研究的3,929对亲本血细胞表型的分位数特异性遗传力(h2) (h2 = 2βOP/[1 + rspouse])。结果:分位数特异性h2(±SE)随子代年龄和性别调整MPV分布的增加而增加(线性= 0.0001):第10个百分位数为0.48±0.09，第25个百分位数为0.53±0.04，第50个百分位数为0.70±0.06，第75个百分位数为0.74±0.06，第90个百分位数为0.90±0.12。分位数特异性h2也随子代白细胞(WBC，线性= 0.002)、单核细胞(线性= 0.01)和嗜酸性粒细胞分布(线性= 0.0005)的增加而增加。相比之下，红细胞(RBC)计数、红细胞压积(HCT)和血红蛋白(HGB)的遗传性几乎没有分位数依赖性的证据。分位数依赖性表达与其他人报道的基因-环境相互作用一致，包括(1)暴露于内毒素时，谷胱甘肽- s -转移酶Mu1 (GSTM1)零纯合子的受试者WBC和PLT浓度比GSTM1充足的受试者增加更多;(2)鞋厂工人低而非高苯暴露时AA纯合子的白细胞计数显著高于谷胱甘肽s -转移酶P1 (GSTP1) rs1695多态性g等位基因携带者;(3)感染性心内膜炎术后TT纯合子白细胞计数高于白细胞介素-1β (il - 1b) c.315C>T多态性c -等位基因携带者。讨论/结论:分位数依赖性表达可以解释几种涉及血细胞表型的基因-环境相互作用。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Lifestyle Genomics Agricultural and Biological Sciences-Food Science

CiteScore

4.00

自引率

7.70%

发文量

审稿时长

28 weeks

期刊介绍： Lifestyle Genomics aims to provide a forum for highlighting new advances in the broad area of lifestyle-gene interactions and their influence on health and disease. The journal welcomes novel contributions that investigate how genetics may influence a person’s response to lifestyle factors, such as diet and nutrition, natural health products, physical activity, and sleep, amongst others. Additionally, contributions examining how lifestyle factors influence the expression/abundance of genes, proteins and metabolites in cell and animal models as well as in humans are also of interest. The journal will publish high-quality original research papers, brief research communications, reviews outlining timely advances in the field, and brief research methods pertaining to lifestyle genomics. It will also include a unique section under the heading “Market Place” presenting articles of companies active in the area of lifestyle genomics. Research articles will undergo rigorous scientific as well as statistical/bioinformatic review to ensure excellence.