Structural variation across 138,134 samples in the TOPMed consortium

Area of Science:

• Genomics
• Human Genetics
• Bioinformatics

Background:

• Structural Variants (SVs) are crucial for understanding human genetic diversity and disease links.
• Accurate identification of SVs from DNA sequencing data presents a significant challenge, requiring a balance between completeness and precision.

Approach:

• Developed and applied advanced methodologies for Structural Variant (SV) inference across autosomes and the X chromosome.
• Generated a comprehensive catalog of 355,667 SVs (50bp+) from 138,134 individuals within the Trans-Omics for Precision Medicine (TOPMed) consortium.
• Validated SV calls with high variant quality and >90% allele concordance against long-read de novo assemblies.

Key Points:

• The catalog includes 59.34% novel SVs, enhancing the understanding of genetic variation.
• Identified 690 SV hotspots and deserts, providing insights into genomic regions prone to structural alterations.
• Demonstrated significant associations between identified SVs and cardio-metabolic and hematologic traits.
• Highlighted SVs potentially impacting the regulation of medically relevant genes.

Conclusions:

• The comprehensive SV catalog from the TOPMed consortium is a valuable resource for genetic research.
• This catalog will advance the understanding of SVs' role in disease development and progression across diverse populations.