Description

Structural variants (SVs), defined as any genomic rearrangements of 50 or more bp, are an important source of genetic diversity and have been linked to many diseases. Here, we report 170,996 SVs which were constructed using 1,760 short-read whole genomes from aging and Alzheimer’s disease subjects. We quantified the impact of cis-acting SVs on several molecular traits (SV-xQTL) including histone modification, gene expression, mRNA splicing, and protein abundance in post-mortem brain tissues. Our study provides a comprehensive view of the mechanisms linking structural variation to gene regulation and provides a valuable resource for understanding the functional impact of SVs in the aged human brain.

Principal Investigators

  • Ricardo A. Vialle — Icahn School of Medicine at Mount Sinai
  • Katia de Paiva Lopes, PhD — Icahn School of Medicine at Mount Sinai
  • David A. Bennett, MD — Rush University
  • John F. Crary, MD, PhD — Icahn School of Medicine at Mount Sinai
  • Towfique Raj, PhD — Icahn School of Medicine at Mount Sinai

Funding Sources

This work was supported by grants from the US National Institutes of Health (NIH NIA U01 AG06888001, NIA R01-AG054005, NIA R56-AG055824, and NIA R01-AG054008).

Publications

  • Vialle RA. Integrating whole-genome sequencing with multi-omic data reveals the impact of structural variants on gene regulation in the human brain. Nature neuroscience. 2022 Apr. PubMed link