Polymorphic short tandem repeats make widespread contributions to blood and serum traits.
Jonathan Margoliash, Shai Fuchs, Yang Li, Xuan Zhang, Arya Massarat, Alon Goren, Melissa Gymrek
Author Information
Jonathan Margoliash: Department of Computer Science and Engineering, University of California, San Diego, La Jolla, CA 92093, USA.
Shai Fuchs: Pediatric Endocrine and Diabetes Unit, Edmond and Lily Safra Children's Hospital, Sheba Medical Center, Ramat Gan, Israel.
Yang Li: Department of Computer Science and Engineering, University of California, San Diego, La Jolla, CA 92093, USA; Department of Medicine, University of California, San Diego, La Jolla, CA 92093, USA.
Xuan Zhang: Department of Medicine, University of California, San Diego, La Jolla, CA 92093, USA.
Arya Massarat: Bioinformatics and Systems Biology Program, University of California, San Diego, La Jolla, CA 92093, USA.
Alon Goren: Department of Medicine, University of California, San Diego, La Jolla, CA 92093, USA. Electronic address: agoren@ucsd.edu.
Melissa Gymrek: Department of Computer Science and Engineering, University of California, San Diego, La Jolla, CA 92093, USA; Department of Medicine, University of California, San Diego, La Jolla, CA 92093, USA. Electronic address: mgymrek@ucsd.edu.
Short tandem repeats (STRs) are genomic regions consisting of repeated sequences of 1-6 bp in succession. Single-nucleotide polymorphism (SNP)-based genome-wide association studies (GWASs) do not fully capture STR effects. To study these effects, we imputed 445,720 STRs into genotype arrays from 408,153 White British UK Biobank participants and tested for association with 44 blood phenotypes. Using two fine-mapping methods, we identify 119 candidate causal STR-trait associations and estimate that STRs account for 5.2%-7.6% of causal variants identifiable from GWASs for these traits. These are among the strongest associations for multiple phenotypes, including a coding CTG repeat associated with apolipoprotein B levels, a promoter CGG repeat with platelet traits, and an intronic poly(A) repeat with mean platelet volume. Our study suggests that STRs make widespread contributions to complex traits, provides stringently selected candidate causal STRs, and demonstrates the need to consider a more complete view of genetic variation in GWASs.
