当前位置: X-MOL 学术Hum. Hered. › 论文详情
Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)
A Family-Based Rare Haplotype Association Method for Quantitative Traits.
Human Heredity ( IF 1.8 ) Pub Date : 2019-02-21 , DOI: 10.1159/000493543
Ananda S Datta 1 , Shili Lin 2 , Swati Biswas 3
Affiliation  

BACKGROUND The variants identified in genome-wide association studies account for only a small fraction of disease heritability. A key to this "missing heritability" is believed to be rare variants. Specifically, we focus on rare haplotype variant (rHTV). The existing methods for detecting rHTV are mostly population-based, and as such, are susceptible to population stratification and admixture, leading to an inflated false-positive rate. Family-based methods are more robust in this respect. METHODS We propose a method for detecting rHTVs associated with quantitative traits called family-based quantitative Bayesian LASSO (famQBL). FamQBL can analyze any type of pedigree and is based on a mixed model framework. We regularize the haplotype effects using Bayesian LASSO and estimate the posterior distributions using Markov chain Monte Carlo methods. RESULTS We conduct simulation studies, including analyses of Genetic Analysis Workshop 18 simulated data, to study the properties of famQBL and compare with a standard family-based haplotype association test implemented in FBAT (family-based association test) software. We find famQBL to be more powerful than FBAT with well-controlled false-positive rates. We also apply famQBL to the Framingham Heart Study data and detect an rHTV associated with diastolic blood pressure. CONCLUSION FamQBL can help uncover rHTVs associated with quantitative traits.

中文翻译:

基于家庭的数量性状的稀有单倍型关联方法。

背景技术在全基因组关联研究中鉴定的变体仅占疾病遗传力的一小部分。据信这种“缺乏遗传力”的关键是罕见的变异。具体来说,我们专注于罕见的单倍型变体(rHTV)。现有的检测rHTV的方法主要是基于人群的,因此容易受到人群分层和混合的影响,从而导致假阳性率升高。基于家庭的方法在这方面更强大。方法我们提出了一种检测与定量性状相关的rHTV的方法,称为基于家庭的定量贝叶斯LASSO(famQBL)。FamQBL可以分析任何类型的谱系,并且基于混合模型框架。我们使用贝叶斯LASSO规范单倍型效应,并使用马尔可夫链蒙特卡洛方法估计后验分布。结果我们进行了模拟研究,包括遗传分析研讨会18模拟数据的分析,以研究famQBL的特性,并与在FBAT(基于家庭的关联测试)软件中实现的基于家庭的标准单倍型关联测试进行比较。我们发现,famQBL具有比FBAT更强大的功能,且误报率得到良好控制。我们还将famQBL应用于Framingham心脏研究数据,并检测与舒张压相关的rHTV。结论FamQBL可以帮助发现与定量性状相关的rHTV。来研究famQBL的特性,并与在FBAT(基于家庭的关联测试)软件中实现的基于家庭的标准单倍型关联测试进行比较。我们发现,famQBL具有比FBAT更强大的功能,且误报率得到良好控制。我们还将famQBL应用于Framingham心脏研究数据,并检测与舒张压相关的rHTV。结论FamQBL可以帮助发现与定量性状相关的rHTV。来研究famQBL的特性,并与在FBAT(基于家庭的关联测试)软件中实现的基于家庭的标准单倍型关联测试进行比较。我们发现,famQBL具有比FBAT更强大的功能,且误报率得到良好控制。我们还将famQBL应用于Framingham心脏研究数据,并检测与舒张压相关的rHTV。结论FamQBL可以帮助发现与定量性状相关的rHTV。
更新日期:2019-11-01
down
wechat
bug