Association testing for next-generation sequencing data using score statistics

Genetic Epidemiology
Line SkotteAnders Albrechtsen

Abstract

The advances in sequencing technology have made large-scale sequencing studies for large cohorts feasible. Often, the primary goal for large-scale studies is to identify genetic variants associated with a disease or other phenotypes. Even when deep sequencing is performed, there will be many sites where there is not enough data to call genotypes accurately. Ignoring the genotype classification uncertainty by basing subsequent analyses on called genotypes leads to a loss in power. Additionally, using called genotypes can lead to spurious association signals. Some methods taking the uncertainty of genotype calls into account have been proposed; most require numerical optimization which for large-scale data is not always computationally feasible. We show that using a score statistic for the joint likelihood of observed phenotypes and observed sequencing data provides an attractive approach to association testing for next-generation sequencing data. The joint model accounts for the genotype classification uncertainty via the posterior probabilities of the genotypes given the observed sequencing data, which gives the approach higher power than methods based on called genotypes. This strategy remains computationally feasible due to t...Continue Reading

References

Jan 16, 2002·American Journal of Human Genetics·Daniel J SchaidGregory A Poland
Jun 19, 2007·Nature Genetics·Jonathan MarchiniPeter Donnelly
Oct 19, 2007·Nature·UNKNOWN International HapMap ConsortiumJohn Stewart
May 8, 2009·Genome Research·Ruiqiang LiJun Wang
May 20, 2009·Bioinformatics·Heng Li, Richard Durbin
Jun 10, 2009·Bioinformatics·Heng LiUNKNOWN 1000 Genome Project Data Processing Subgroup
Nov 17, 2009·Nature Genetics·Sarah B NgMichael J Bamshad
Jun 17, 2010·Genetic Epidemiology·Su Yeon KimRasmus Nielsen
Oct 29, 2010·Nature·Gonçalo R AbecasisGil A McVean
Feb 18, 2011·Genetic Epidemiology·Chad Garner

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Citations

Oct 4, 2013·BMC Bioinformatics·Thorfinn Sand KorneliussenRasmus Nielsen
Nov 26, 2014·BMC Bioinformatics·Thorfinn KorneliussenRasmus Nielsen
Mar 24, 2015·Nature Methods·Ricardo Cruz-Herrera del RosarioShyam Prabhakar
Jan 13, 2015·Trends in Genetics : TIG·Jason A O'RaweGholson J Lyon
Jun 22, 2019·Scientific Reports·Mikkel SkovrindEline D Lorenzen
Aug 23, 2018·Genetics·Jonas Meisner, Anders Albrechtsen
Jul 8, 2021·Molecular Ecology·Gabriela Montejo-KovacevichNicola J Nadeau
Jul 13, 2021·Molecular Ecology·Runyang Nicolas LouNina Overgaard Therkildsen

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