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.jpg): Failed to open stream: No such file or directory in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 117 Genet+Epidemiol
2017 ; 41
(2
): 152-162
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Impact of genotyping errors on statistical power of association tests in genomic
analyses: A case study
#MMPMID28019059
Hou L
; Sun N
; Mane S
; Sayward F
; Rajeevan N
; Cheung KH
; Cho K
; Pyarajan S
; Aslan M
; Miller P
; Harvey PD
; Gaziano JM
; Concato J
; Zhao H
Genet Epidemiol
2017[Feb]; 41
(2
): 152-162
PMID28019059
show ga
A key step in genomic studies is to assess high throughput measurements across
millions of markers for each participant's DNA, either using microarrays or
sequencing techniques. Accurate genotype calling is essential for downstream
statistical analysis of genotype-phenotype associations, and next generation
sequencing (NGS) has recently become a more common approach in genomic studies.
How the accuracy of variant calling in NGS-based studies affects downstream
association analysis has not, however, been studied using empirical data in which
both microarrays and NGS were available. In this article, we investigate the
impact of variant calling errors on the statistical power to identify
associations between single nucleotides and disease, and on associations between
multiple rare variants and disease. Both differential and nondifferential
genotyping errors are considered. Our results show that the power of burden tests
for rare variants is strongly influenced by the specificity in variant calling,
but is rather robust with regard to sensitivity. By using the variant calling
accuracies estimated from a substudy of a Cooperative Studies Program project
conducted by the Department of Veterans Affairs, we show that the power of
association tests is mostly retained with commonly adopted variant calling
pipelines. An R package, GWAS.PC, is provided to accommodate power analysis that
takes account of genotyping errors (http://zhaocenter.org/software/).