Assessing the Heritability of Complex Traits in Humans: Methodological Challenges and Opportunities.

Assessing the Heritability of Complex Traits in Humans: Methodological Challenges and Opportunities.
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DOI:
10.2174/1389202918666170307161450
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发表时间:
2017-08
期刊:
影响因子:
2.6
通讯作者:
Meyre D
Meyre D
中科院分区:
生物学4区
文献类型:
--
作者:
Mayhew AJ;Meyre D

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这篇综述文章的目的是对如何确定复杂性状(如肥胖)的遗传力估计提供一个基于概念的总结,并探讨遗传力领域的未来研究方向。目标受众是使用遗传数据的研究人员,而不是进行遗传研究的研究人员。本文介绍了理解遗传力研究的关键概念,包括:1)遗传力的定义:广义遗传力与狭义遗传力;Ii)如何收集遗传性研究的数据:双胞胎、收养、家庭和基于人口的研究;分析技术:路径分析、结构方程和混合或回归模型的复杂偏析分析。对于每个部分,提供了不同定义和方法如何影响遗传力估计的讨论。讨论了遗传力研究的一般局限性,包括“缺失遗传力”问题,其中遗传力估计明显高于已知遗传变异解释的方差。遗传力缺失的潜在原因包括许多遗传关联研究局限于单核苷酸多态性、基因与基因相互作用、表观遗传学和基因与环境相互作用。讨论了缺失遗传力核算的创新策略,包括建模技术和改进的软件。
The goal of this review article is to provide a conceptual based summary of how heritability estimates for complex traits such as obesity are determined and to explore the future directions of research in the heritability field. The target audience are researchers who use heritability data rather than those conducting heritability studies. The article provides an introduction to key concepts critical to understanding heritability studies including: i) definitions of heritability: broad sense versus narrow sense heritability; ii) how data for heritability studies are collected: twin, adoption, family and population-based studies; and iii) analytical techniques: path analysis, structural equations and mixed or regressive models of complex segregation analysis. For each section, a discussion of how the different definitions and methodologies influence heritability estimates is provided. The general limitations of heritability studies are discussed including the issue of “missing heritability” in which heritability estimates are significantly higher than the variance explained by known genetic variants. Potential causes of missing heritability include restriction of many genetic association studies to single nucleotide polymorphisms, gene by gene interactions, epigenetics, and gene by environment interactions. Innovative strategies of accounting for missing heritability including modeling techniques and improved software are discussed.
DOI: 10.1186/1297-9686-44-16
发表时间: 2012-05-08
影响因子: 4.1
作者:
Odegard, Jorgen;Meuwissen, Theo H. E.
通讯作者: Meuwissen, Theo H. E.
DOI: 10.1038/nature14177
发表时间: 2015-02-12
期刊: NATURE
影响因子: 64.8
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通讯作者: Speliotes, Elizabeth K.
DOI: 10.2307/2531211
发表时间: 1986-09-01
期刊: BIOMETRICS
影响因子: 1.9
作者:
BONNEY, GE
通讯作者: BONNEY, GE
DOI: 10.1093/bioinformatics/btr219
发表时间: 2011-07-01
期刊: Bioinformatics (Oxford, England)
影响因子: --
作者:
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通讯作者: Rosset S
DOI: 10.1002/ajmg.1320180420
发表时间: 1984-01-01
期刊: AMERICAN JOURNAL OF MEDICAL GENETICS
影响因子: --
作者:
BONNEY, GE
通讯作者: BONNEY, GE