ArticleGenetic epidemiology2014
Power of family-based association designs to detect rare variants in large pedigrees using imputed genotypes.
Article in Genetic epidemiology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers, 1 of them a synthesis that pooled it.
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Who cites it
24 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Methods for association analysis and meta-analysis of rare variants in families.Genetic epidemiology · 2015Pooled it
- Adjustment for Genotype Imputation Uncertainty Corrects for Inflated Type I Error in Family-Based Association Testing.Genetic epidemiology · 2025Article
- A pedigree-based cohort to study the genetic risk factors for cardiometabolic diseases: study design, baseline characteristics and preliminary results.Frontiers in public health · 2023Article
- Accuracy of genotype imputation based on reference population size and marker density in Hanwoo cattle.Journal of animal science and technology · 2021Article
- Alternative Applications of Genotyping Array Data Using Multivariant Methods.Trends in genetics : TIG · 2020Review
- Next Generation Sequencing and Bioinformatics Analysis of Family Genetic Inheritance.Frontiers in genetics · 2020Review
- Rediscovering the value of families for psychiatric genetics research.Molecular psychiatry · 2019Review
- Revisit Population-based and Family-based Genotype Imputation.Scientific reports · 2019Article
- Comparison and assessment of family- and population-based genotype imputation methods in large pedigrees.Genome research · 2019Article
- Genome-wide linkage and association analysis of cardiometabolic phenotypes in Hispanic Americans.Journal of human genetics · 2017Article
- PADRE: Pedigree-Aware Distant-Relationship Estimation.American journal of human genetics · 2016Article
- FamPipe: An Automatic Analysis Pipeline for Analyzing Sequencing Data in Families for Disease Studies.PLoS computational biology · 2016Article
- Genome-wide linkage on chromosome 10q26 for a dimensional scale of major depression.Journal of affective disorders · 2016Article
- Rare Variants in NOD1 Associated with Carotid Bifurcation Intima-Media Thickness in Dominican Republic Families.PloS one · 2016Article
- Transmission and decorrelation methods for detecting rare variants using sequencing data from related individuals.BMC proceedings · 2016Article
- PBAP: a pipeline for file processing and quality control of pedigree data with dense genetic markers.Bioinformatics (Oxford, England) · 2015Article
- Whole exome sequencing in extended families with autism spectrum disorder implicates four candidate genes.Human genetics · 2015Article
- Reproducible simulations of realistic samples for next-generation sequencing studies using Variant Simulation Tools.Genetic epidemiology · 2015Article
- Combining family- and population-based imputation data for association analysis of rare and common variants in large pedigrees.Genetic epidemiology · 2014Article
- Flexible and robust methods for rare-variant testing of quantitative traits in trios and nuclear families.Genetic epidemiology · 2014Article
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2 authors.
Funding
Abstract
Recently, the "Common Disease-Multiple Rare Variants" hypothesis has received much attention, especially with current availability of next-generation sequencing. Family-based designs are well suited for discovery of rare variants, with large and carefully selected pedigrees enriching for multiple copies of such variants. However, sequencing a large number of samples is still prohibitive. Here, we evaluate a cost-effective strategy (pseudosequencing) to detect association with rare variants in large pedigrees. This strategy consists of sequencing a small subset of subjects, genotyping the remaining sampled subjects on a set of sparse markers, and imputing the untyped markers in the remaining subjects conditional on the sequenced subjects and pedigree information. We used a recent pedigree imputation method (GIGI), which is able to efficiently handle large pedigrees and accurately impute rare variants. We used burden and kernel association tests, famWS and famSKAT, which both account for family relationships and heterogeneity of allelic effect for famSKAT only. We simulated pedigree sequence data and compared the power of association tests for pseudosequence data, a subset of sequence data used for imputation, and all subjects sequenced. We also compared, within the pseudosequence data, the power of association test using best-guess genotypes and allelic dosages. Our results show that the pseudosequencing strategy considerably improves the power to detect association with rare variants. They also show that the use of allelic dosages results in much higher power than use of best-guess genotypes in these family-based data. Moreover, famSKAT shows greater power than famWS in most of scenarios we considered.
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