title: Abundant contribution of short tandem repeats to gene expression variation in humans.
abstract: The contribution of repetitive elements to quantitative human traits is largely unknown. Here we report a genome-wide survey of the contribution of short tandem repeats (STRs), which constitute one of the most polymorphic and abundant repeat classes, to gene expression in humans. Our survey identified 2,060 significant expression STRs (eSTRs). These eSTRs were replicable in orthogonal populations and expression assays. We used variance partitioning to disentangle the contribution of eSTRs from that of linked SNPs and indels and found that eSTRs contribute 10-15% of the cis heritability mediated by all common variants. Further functional genomic analyses showed that eSTRs are enriched in conserved regions, colocalize with regulatory elements and may modulate certain histone modifications. By analyzing known genome-wide association study (GWAS) signals and searching for new associations in 1,685 whole genomes from deeply phenotyped individuals, we found that eSTRs are enriched in various clinically relevant conditions. These results highlight the contribution of STRs to the genetic architecture of quantitative human traits.
authors.affiliation: Whitehead Institute for Biomedical Research, Cambridge, Massachusetts, USA.|Harvard-MIT Division of Health Sciences and Technology, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA.|Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA.|New York Genome Center, New York, New York, USA.
authors.forename: Melissa
authors.initials: M
authors.lastname: Gymrek
authors.affiliation: Whitehead Institute for Biomedical Research, Cambridge, Massachusetts, USA.|New York Genome Center, New York, New York, USA.|Computational and Systems Biology Program, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA.
authors.forename: Thomas
authors.initials: T
authors.lastname: Willems
authors.affiliation: Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, New York, USA.|Department of Pediatric Hematology, Robert Debré Hospital, Paris, France.
authors.forename: Audrey
authors.initials: A
authors.lastname: Guilmatre
authors.affiliation: Computer Science and Artificial Intelligence Laboratory, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA.
authors.forename: Haoyang
authors.initials: H
authors.lastname: Zeng
authors.affiliation: Whitehead Institute for Biomedical Research, Cambridge, Massachusetts, USA.
authors.forename: Barak
authors.initials: B
authors.lastname: Markus
authors.affiliation: Department of Genetics and Biology, Stanford University, Stanford, California, USA.
authors.forename: Stoyan
authors.initials: S
authors.lastname: Georgiev
authors.affiliation: Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA.|Analytic and Translational Genetics Unit, Massachusetts General Hospital, Boston, Massachusetts, USA.
authors.forename: Mark J
authors.initials: MJ
authors.lastname: Daly
authors.affiliation: Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA.|Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, USA.|Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, USA.
authors.forename: Alkes L
authors.initials: AL
authors.lastname: Price
authors.affiliation: Department of Genetics and Biology, Stanford University, Stanford, California, USA.|Howard Hughes Medical Institute, Chevy Chase, Maryland, USA.
authors.forename: Jonathan K
authors.initials: JK
authors.lastname: Pritchard
authors.affiliation: Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Sharp
authors.affiliation: Whitehead Institute for Biomedical Research, Cambridge, Massachusetts, USA.|New York Genome Center, New York, New York, USA.|Department of Computer Science, Fu Foundation School of Engineering, Columbia University, New York, New York, USA.|Center for Computational Biology and Bioinformatics, Columbia University, New York, New York, USA.
authors.forename: Yaniv
authors.initials: Y
authors.lastname: Erlich
mesh_terms: D003424:Crohn Disease / Q000235:genetics; D015870:Gene Expression; D014644:Genetic Variation; D015894:Genome, Human; D055106:Genome-Wide Association Study; D006657:Histones / Q000235:genetics / Q000378:metabolism; D006801:Humans; D054643:INDEL Mutation; D018895:Microsatellite Repeats; D008957:Models, Genetic; D020641:Polymorphism, Single Nucleotide; D040641:Quantitative Trait Loci; D012045:Regulatory Sequences, Nucleic Acid; D014427:Twins / Q000235:genetics
chemical_list: D006657:Histones