Unrecognized sequence homologies may confound genome-wide association studies.

Nucleic Acids Research
Pierre GalichonEric Rondeau

Abstract

Genome-wide association studies (GWAS) have become a preferred method to identify new genetic susceptibility loci. This technique aims to understanding the molecular etiology of common diseases, but in many cases, it has led to the identification of loci with no obvious biological relevance. Herein, we show that previously unrecognized sequence homologies have caused single-nucleotide polymorphism (SNP) microarrays to incorrectly associate a phenotype to a given locus when in fact the linkage is to another distant locus. Using genetic differences between male and female subjects as a model to study the effect of one specific genomic region on the whole SNP microarray, we provide strong evidence that the use of standard methods for GWAS can be misleading. We suggest a new systematic quality control step in the biological interpretation of previous and future GWAS.

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Citations

Apr 28, 2020·Molecular Ecology·Changde Cheng, Mark Kirkpatrick
Oct 18, 2019·PloS One·Lyle G BestV Saroja Voruganti
Oct 20, 2020·Development and Psychopathology·Karen J MathewsonLouis A Schmidt
Aug 20, 2021·Interdisciplinary Sciences, Computational Life Sciences·An ZengUNKNOWN Alzheimer’s Disease Neuroimaging Initiative (ADNI)

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Methods Mentioned

BETA
genotyping
chip
chips

Software Mentioned

PLINK
Basic Local Alignment Search Tool ( BLAST )
R
BLAST
Maste
ClassComparison
BlastN
Affymetrix

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