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Genetic variation affecting temporal patterns of gene expression and disease in human brain (776.1)
Author(s) -
Fraser Hunter,
Martin Trevor
Publication year - 2014
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.28.1_supplement.776.1
Subject(s) - biology , expression quantitative trait loci , gene , genetics , genetic variation , enhancer , phenotype , gene expression , genome wide association study , disease , quantitative trait locus , dna methylation , single nucleotide polymorphism , allele , regulation of gene expression , human genome , genetic architecture , genome , genotype , medicine , pathology
It is widely recognized that noncoding regions of the human genome, including those controlling the cis‐regulation of gene expression, harbor most disease‐associated genetic variants and most regions under selective constraint. Although the expression of many genes is a dynamic process that changes during an organism’s lifetime, most studies mapping genetic variants affecting gene expression have either ignored the variation in ages among individuals, or treated it as a confounding variable. Here we introduce a method for mapping genetic variants that affect the developmental timing of gene expression, which we call temporal expression quantitative trait loci (teQTL). Applying this approach to human prefrontal cortex, we found several thousand genes associated with teQTLs. These teQTLs are distinct from variants affecting expression levels throughout life, and are often associated with distal transcriptional enhancers or age‐related changes in DNA methylation. Moreover they coincide with dozens of SNPs previously implicated in neurological traits such as Alzheimer’s disease, Parkinson’s disease, and educational attainment. These results suggest that teQTLs are a widespread source of variation in human neurological phenotypes. Grant Funding Source : Supported by the Pew Foundation