Common genetic variants associated with urinary phthalate levels in children: a genome-wide study

Abstract

IntroductionPhthalates, or dieters of phthalic acid, are a ubiquitous type of plasticizer used in a variety of common consumer and industrial products. They act as endocrine disruptors and are associated with increased risk for several diseases. Once in the body, phthalates are metabolized through partially known mechanisms, involving phase I and phase II enzymes. ObjectiveIn this study we aimed to identify common single nucleotide polymorphisms (SNPs) and copy number variants (CNVs) associated with the metabolism of phthalate compounds in children through genome-wide association studies (GWAS). MethodsThe study used data from 1,044 children with European ancestry from the Human Early Life Exposome (HELIX) cohort. Ten phthalate metabolites were assessed in a two-void urine pool collected at the mean age of 8 years. Six ratios between secondary and primary phthalate metabolites were calculated. Genome-wide genotyping was done with the Infinium Global Screening Array (GSA) and imputation with the Haplotype Reference Consortium (HRC) panel. PennCNV was used to estimate copy number variants (CNVs) and CNVRanger to identify consensus regions. GWAS of SNPs and CNVs were conducted using PLINK and SNPassoc, respectively. Subsequently, functional annotation of suggestive SNPs (p-value View larger version (23K): org.highwire.dtl.DTLVardef@2ff3c6org.highwire.dtl.DTLVardef@2d83a7org.highwire.dtl.DTLVardef@1e69dborg.highwire.dtl.DTLVardef@b7e051_HPS_FORMAT_FIGEXP M_FIG C_FIG HighlightsO_LIThe genetic variation involved in phthalate detoxification in humans is partially known. C_LIO_LIWe identified four loci at genome-wide significance, and 113 at suggestive significance, some of them being novel. C_LIO_LITwo copy number variants were also identified. C_LIO_LIFunctional annotation highlighted genes in phase I and II detoxification and renal excretion. C_LI