Structural Variant Imputation in Samoans Using a Population-Specific Reference Panel

Area of Science:

• Genomics
• Population Genetics
• Bioinformatics

Background:

• Structural variants (SVs) are crucial for phenotypic traits but often excluded from genetic studies due to calling difficulties.
• Samoans, an understudied population with high complex disease burden, lack comprehensive SV characterization.
• Accurate genetic imputation is vital for understanding disease associations in diverse populations.

Purpose of the Study:

• To characterize structural variants (SVs) in the Samoan population.
• To develop a Samoan-specific reference panel including SVs and single nucleotide variants (SNVs) for improved genetic imputation.
• To assess the impact of population-specific SVs on imputation accuracy and SV-phenotype associations.

Main Methods:

• Whole genome sequencing of 1,276 Samoans to identify structural variants (SVs).
• Creation of the Samoan-specific 'Soifua Manuia-SV' imputation panel.
• Imputation of SVs and SNVs in 3,611 Samoans using array data and comparison against other reference panels.

Main Results:

• The 'Soifua Manuia-SV' panel significantly outperformed a multi-ancestry panel, yielding 5.5 million more high-quality variants, including over 8,000 additional high-quality SVs.
• SNV imputation accuracy was similar between Samoan-specific panels, indicating SV inclusion does not significantly degrade SNV imputation.
• The study demonstrates the critical need for population-specific reference panels for accurate genetic imputation.

Conclusions:

• Population representation in reference panels is essential for high-quality genetic imputation, especially for understudied groups like Samoans.
• The 'Soifua Manuia-SV' panel enhances the ability to study SVs and their impact on complex diseases in Samoans.
• This work provides a valuable resource for future genetic research in Polynesian populations.