Structural variants caused by Alu insertions are associated with risks for many human diseases

Lindsay M. Payer, Jared P. Steranka, Wan Rou Yang, Maria Kryatova, Sibyl Medabalimi, Daniel Ardeljan, Chunhong Liu, Jef D. Boeke, Dimitri Avramopoulos, Kathleen H. Burns

Research output: Contribution to journalArticlepeer-review


Interspersed repeat sequences comprise much of our DNA, although their functional effects are poorly understood. The most commonly occurring repeat is the Alu short interspersed element. New Alu insertions occur in human populations, and have been responsible for several instances of genetic disease. In this study, we sought to determine if there are instances of polymorphic Alu insertion variants that function in a common variant, common disease paradigm. We cataloged 809 polymorphic Alu elements mapping to 1,159 loci implicated in disease risk by genome-wide association study (GWAS) (P < 10-8). We found that Alu insertion variants occur disproportionately at GWAS loci (P = 0.013). Moreover, we identified 44 of these Alu elements in linkage disequilibrium (r2 > 0.7) with the trait-associated SNP. This figure represents a >20-fold increase in the number of polymorphic Alu elements associated with human phenotypes. This work provides a broader perspective on how structural variants in repetitive DNAs may contribute to human disease.

Original languageEnglish (US)
Pages (from-to)E3984-E3992
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number20
StatePublished - May 16 2017


  • Alu
  • Causative variant
  • GWAS
  • Interspersed repeats
  • Structural variant

ASJC Scopus subject areas

  • General


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