期刊
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
卷 114, 期 20, 页码 E3984-E3992出版社
NATL ACAD SCIENCES
DOI: 10.1073/pnas.1704117114
关键词
Alu; structural variant; GWAS; causative variant; interspersed repeats
资金
- National Heart, Lung, and Blood Institute [T32HL007525]
- Burroughs Wellcome Fund Career Award for Biomedical Scientists Program
- US NIH [R01CA163705, R01GM103999]
- Center for Systems Biology of Retrotransposition [P50GM107632]
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). More-over, we identified 44 of these Alu elements in linkage disequilibrium (r(2) > 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.
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