Unrecognized sequence homologies may confound genome-wide association studies.

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.

journal_name

Nucleic Acids Res

journal_title

Nucleic acids research

authors

Galichon P,Mesnard L,Hertig A,Stengel B,Rondeau E

doi

10.1093/nar/gks169

subject

Has Abstract

pub_date

2012-06-01 00:00:00

pages

4774-82

issue

11

eissn

0305-1048

issn

1362-4962

pii

gks169

journal_volume

40

pub_type

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