title: 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.
authors.affiliation: INSERM UMR S702, Université Pierre et Marie Curie - Paris 6, 75006 Paris, France. galichon@orange.fr
authors.forename: Pierre
authors.initials: P
authors.lastname: Galichon
authors.forename: Laurent
authors.initials: L
authors.lastname: Mesnard
authors.forename: Alexandre
authors.initials: A
authors.lastname: Hertig
authors.forename: Bénédicte
authors.initials: B
authors.lastname: Stengel
authors.forename: Eric
authors.initials: E
authors.lastname: Rondeau
mesh_terms: D004247:DNA / Q000737:chemistry; D005260:Female; D056426:Genetic Loci; D055106:Genome-Wide Association Study; D006801:Humans; D008297:Male; D020641:Polymorphism, Single Nucleotide; D012689:Sequence Homology, Nucleic Acid; D012730:Sex Chromosomes; D012737:Sex Factors
chemical_list: D004247:DNA