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 diversity and disease.
• Accurate and comprehensive SV identification from DNA sequencing data is challenging.

Approach:

• Generated a catalog of 355,667 SVs (≥50bp) from 138,134 individuals in the TOPMed consortium.
• Employed advanced methodologies for SV inference, achieving high variant quality and >90% allele concordance with long-read assemblies.
• Identified SV hotspots, deserts, and regulatory impacts on medically relevant genes.

Key Points:

• The catalog includes 59.34% novel SVs across autosomes and the X chromosome.
• Demonstrated significant associations between SVs and cardio-metabolic/hematologic traits.
• Characterized 690 SV hotspots and deserts.

Conclusions:

• This comprehensive SV catalog from a diverse population is a valuable resource for disease research.
• Facilitates understanding the role of SVs in disease development and progression.
• Enables further investigation into the functional impact of SVs on gene regulation.