General retrospective mega-analysis framework for rare variant association tests

2018 ◽  
Vol 42 (7) ◽  
pp. 621-635
Author(s):  
Li-Chu Chien ◽  
Yen-Feng Chiu
Keyword(s):  
Rare Variant ◽  
Analysis Framework ◽  
Rare Variant Association ◽  
Association Tests

scholarly journals Pooled Sequencing and Rare Variant Association Tests for Identifying the Determinants of Emerging Drug Resistance in Malaria Parasites

2015 ◽  
Vol 32 (4) ◽  
pp. 1080-1090 ◽  
Author(s):  
Ian H. Cheeseman ◽  
Marina McDew-White ◽  
Aung Pyae Phyo ◽  
Kanlaya Sriprawat ◽  
François Nosten ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Rare Variant ◽  
Malaria Parasites ◽  
Rare Variant Association ◽  
Association Tests ◽  
Pooled Sequencing

scholarly journals Whole-exome sequencing and gene-based rare variant association tests suggest that PLA2G4E might be a risk gene for panic disorder

2018 ◽  
Vol 8 (1) ◽  
Author(s):  
Yoshiro Morimoto ◽  
Mihoko Shimada-Sugimoto ◽  
Takeshi Otowa ◽  
Shintaro Yoshida ◽  
Akira Kinoshita ◽  
...  
Keyword(s):  
Panic Disorder ◽  
Exome Sequencing ◽  
Whole Exome Sequencing ◽  
Rare Variant ◽  
Rare Variant Association ◽  
Association Tests ◽  
Risk Gene ◽  
Whole Exome

scholarly journals Rare-variant association tests in longitudinal studies, with an application to the Multi-Ethnic Study of Atherosclerosis (MESA)

2017 ◽  
Vol 41 (8) ◽  
pp. 801-810 ◽  
Author(s):  
Zihuai He ◽  
Seunggeun Lee ◽  
Min Zhang ◽  
Jennifer A. Smith ◽  
Xiuqing Guo ◽  
...  
Keyword(s):  
Longitudinal Studies ◽  
Rare Variant ◽  
Rare Variant Association ◽  
Association Tests ◽  
Ethnic Study

scholarly journals Population Genetic Simulations of Complex Phenotypes with Implications for Rare Variant Association Tests

2014 ◽  
Vol 39 (1) ◽  
pp. 35-44 ◽  
Author(s):  
Lawrence H. Uricchio ◽  
Raul Torres ◽  
John S. Witte ◽  
Ryan D. Hernandez
Keyword(s):  
Rare Variant ◽  
Population Genetic ◽  
Rare Variant Association ◽  
Association Tests ◽  
Complex Phenotypes

scholarly journals A general approach for combining diverse rare variant association tests provides improved robustness across a wider range of genetic architectures

2015 ◽  
Vol 24 (5) ◽  
pp. 767-773 ◽  
Author(s):  
Brian Greco ◽  
Allison Hainline ◽  
Jaron Arbet ◽  
Kelsey Grinde ◽  
Alejandra Benitez ◽  
...  
Keyword(s):  
Rare Variant ◽  
Rare Variant Association ◽  
Association Tests

scholarly journals Comparing family-based rare variant association tests for dichotomous phenotypes

2016 ◽  
Vol 10 (S7) ◽  
Author(s):  
Longfei Wang ◽  
Sungkyoung Choi ◽  
Sungyoung Lee ◽  
Taesung Park ◽  
Sungho Won
Keyword(s):  
Rare Variant ◽  
Rare Variant Association ◽  
Association Tests ◽  
Family Based

scholarly journals Robust Rare-Variant Association Tests for Quantitative Traits in General Pedigrees

2017 ◽  
Vol 10 (3) ◽  
pp. 491-505
Author(s):  
Yunxuan Jiang ◽  
Karen N. Conneely ◽  
Michael P. Epstein
Keyword(s):  
Rare Variant ◽  
Quantitative Traits ◽  
Rare Variant Association ◽  
Association Tests

scholarly journals Selection and explosive growth may hamper the performance of rare variant association tests

2015 ◽  
Author(s):  
Lawrence H. Uricchio ◽  
John S. Witte ◽  
Ryan D. Hernandez
Keyword(s):  
Natural Selection ◽  
Rare Variant ◽  
Complex Traits ◽  
Statistical Power ◽  
Rare Variants ◽  
Model Parameters ◽  
Phenotypic Variance ◽  
Additive Variance ◽  
Rare Variant Association ◽  
Association Tests

Much recent debate has focused on the role of rare variants in complex phenotypes. However, it is well known that rare alleles can only contribute a substantial proportion of the phenotypic variance when they have much larger effect sizes than common variants, which is most easily explained by natural selection constraining trait-altering alleles to low frequency. It is also plausible that demographic events will influence the genetic architecture of complex traits. Unfortunately, most rare variant association tests do not explicitly model natural selection or non-equilibrium demography. Here, we develop a novel evolutionary model of complex traits. We perform numerical calculations and simulate phenotypes under this model using inferred human demographic and selection parameters. We show that rare variants only contribute substantially to complex traits under very strong assumptions about the relationship between effect size and selection strength. We then assess the performance of state-of-the-art rare variant tests using our simulations across a broad range of model parameters. Counterintuitively, we find that statistical power is lowest when rare variants make the greatest contribution to the additive variance, and that power is substantially lower under our model than previously studied models. While many empirical studies have attempted to identify causal loci using rare variant association methods, few have reported novel associations. Some authors have interpreted this to mean that rare variants contribute little to heritability, but our results show that an alternative explanation is that rare variant tests have less power than previously estimated.

scholarly journals Correction: Multiple Regression Methods Show Great Potential for Rare Variant Association Tests

PLoS ONE ◽  
2013 ◽  
Vol 8 (3) ◽  
Author(s):  
ChangJiang Xu ◽  
Martin Ladouceur ◽  
Zari Dastani ◽  
J. Brent Richards ◽  
Antonio Ciampi ◽  
...  
Keyword(s):  
Multiple Regression ◽  
Rare Variant ◽  
Rare Variant Association ◽  
Association Tests ◽  
Regression Methods
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