Fast Genome‐Wide QTL Association Mapping on Pedigree and Population Data

@article{Zhou2017FastGQ,
  title={Fast Genome‐Wide QTL Association Mapping on Pedigree and Population Data},
  author={Hua Zhou and John Blangero and Thomas D. Dyer and Kei Hang Katie Chan and Kenneth L. Lange and Eric M. Sobel},
  journal={Genetic Epidemiology},
  year={2017},
  volume={41}
}
Since most analysis software for genome‐wide association studies (GWAS) currently exploit only unrelated individuals, there is a need for efficient applications that can handle general pedigree data or mixtures of both population and pedigree data. Even datasets thought to consist of only unrelated individuals may include cryptic relationships that can lead to false positives if not discovered and controlled for. In addition, family designs possess compelling advantages. They are better… 
Genome-wide QTL and eQTL analyses using Mendel
TLDR
Assessment of pedigree genome-wide association studies (GWAS) capabilities on genetics analysis workshop 19 (GAW19) sequencing data and simulated and real phenotypes for both family and random sample data sets are analyzed.
Fast and flexible linear mixed models for genome-wide genetics
TLDR
Improved accuracy for genetic association tests, increased power to discover causal genetic variants, and the ability to provide accurate summaries of model uncertainty using both simulated and real data examples are demonstrated.
The relevance of pedigrees in the conservation genomics era
TLDR
It is argued that pedigrees remain a relevant tool, and when combined with genomic data, create an invaluable resource for conservation genomic management.
On the impact of relatedness on SNP association analysis
TLDR
Stronger relatedness as well as higher heritability result in increased variance of the effect estimate of simple linear regression analysis, providing a simple formula for estimating variance inflation given the relatedness structure and the heritability of a trait of interest.
Heritability of inter-pack aggression in a wild pedigreed population of North American gray wolves.
TLDR
The incredible utility of a pedigreed natural population for dissecting a complex, fitness-related behavioral trait is presented and strong effects of breeding status and relative pack size on aggression are found.
OpenMendel: a cooperative programming project for statistical genetics
TLDR
The OpenMendel project aims to enable interactive and reproducible analyses with informative intermediate results, scale to big data analytics, embrace parallel and distributed computing, adapt to rapid hardware evolution, allow cloud computing, and allow integration of varied genetic data types.
Reliable Learning of Bernoulli Mixture Models
TLDR
A set of sufficient conditions for reliable clustering of data produced by Bernoulli Mixture Models, when the number of clusters is unknown is derived, such that the existence of a clustering algorithm with a sufficient accuracy is guaranteed.
Heritability of interpack aggression in a wild pedigreed population of North American grey wolves
vonHoldt and DeCandia authors contributed equally. 1Ecology and Evolutionary Biology, Princeton University, Princeton, NJ, USA 2BioKnow Health Informatics Lab, College of Life Sciences, Jilin
Reliable clustering of Bernoulli mixture models
TLDR
This paper stipulates a set of conditions on the sample complexity and dimension of the model in order to guarantee the Probably Approximately Correct (PAC)-clusterability of a dataset.
The Quantitative‐MFG Test: A Linear Mixed Effect Model to Detect Maternal‐Offspring Gene Interactions
TLDR
The quantitative‐MFG (QMFG) test is presented, a linear mixed model where maternal and offspring genotypes are fixed effects and residual correlations between family members are random effects, and it is demonstrated that the QMFG score test is an effective and rapid screening tool.
...
...

References

SHOWING 1-10 OF 62 REFERENCES
Family-based association tests for genomewide association scans.
TLDR
A computationally efficient approach to testing association between SNPs and quantitative phenotypes, which can be applied to whole-genome association scans and allows estimation of missing genotypes, resulting in substantial increases in power when genotyping resources are limited.
Variance component model to account for sample structure in genome-wide association studies
TLDR
A variance component approach implemented in publicly available software, EMMA eXpedited (EMMAX), that reduces the computational time for analyzing large GWAS data sets from years to hours is reported.
Family-based designs for genome-wide association studies
TLDR
Next-generation sequencing tools will benefit genetic studies by improving the power of family-based approaches by improvingThe interface between linkage and association analysis is guided and useful guidelines for applications are provided.
Genomewide Rapid Association Using Mixed Model and Regression: A Fast and Simple Method For Genomewide Pedigree-Based Quantitative Trait Loci Association Analysis
TLDR
A novel approach for genomewide pedigree-based quantitative trait loci (QTL) association analysis:genomewide rapid association using mixed model and regression (GRAMMAR), which first obtains residuals adjusted for family effects and subsequently analyzes the association between residuals and genetic polymorphisms using rapid least-squares methods.
A Genomic Background Based Method for Association Analysis in Related Individuals
TLDR
This study considers a situation when study participants are genetically related and proposes a fast two-step method called Genome-wide Association using Mixed Model and Regression (GRAMMAR) for the analysis of pedigree-based quantitative traits.
Family-based association studies for next-generation sequencing.
A mixed-model approach for genome-wide association studies of correlated traits in structured populations
TLDR
This work extends this linear mixed-model approach to carry out GWAS of correlated phenotypes, deriving a fully parameterized multi-Trait mixed model (MTMM) that considers both the within-trait and between-traits variance components simultaneously for multiple traits.
Case-control association testing with related individuals: a more powerful quasi-likelihood score test.
TLDR
A novel test, the MQLS test, is proposed, which represents an overall, and in many cases, substantial, improvement in power over previous tests, while retaining a computational simplicity that makes it useful in genomewide association studies in arbitrary pedigrees.
A comparison of strategies for analyzing dichotomous outcomes in genome‐wide association studies with general pedigrees
TLDR
Simulation studies show that generalized estimating equations strategies with various working correlation structures, generalized linear mixed model (GLMM), and a variance component strategy (denoted LMEBIN) that treats dichotomous outcomes as continuous with special attentions to their performance with rare variants, rare diseases, and small sample sizes have similar statistical power and slightly outperform GLMM when the prevalence is low.
...
...