SEAD reference panel with 22,134 haplotypes boosts rare variant imputation and genome-wide association analysis in...

Area of Science:

• Genomics
• Population Genetics
• Human Genetics

Background:

• Limited whole genome sequencing studies in Asian populations result in a lack of representative reference panels.
• This deficiency hinders the discovery of ancestry-specific genetic variants and associations.

Purpose of the Study:

• To develop a comprehensive reference panel for South and East Asian populations.
• To improve genetic imputation accuracy and facilitate the discovery of novel genetic associations in these populations.

Main Methods:

• Integrated whole genome sequencing data from 11,067 individuals across 17 Asian countries to create the SEAD panel.
• Evaluated imputation accuracy of the SEAD panel against existing reference panels (1000 Genomes, TOPMed, ChinaMAP).
• Applied the SEAD panel to a genome-wide association study for total hip and femoral neck bone mineral density in Chinese samples.

Main Results:

• The SEAD panel demonstrated superior imputation accuracy for South Asian populations compared to existing panels.
• SEAD showed comparable or better imputation accuracy for East Asian populations.
• A novel association between rare variants near SNTG1 and hip bone mineral density was identified in Chinese samples, detectable only with Asian-specific panels.

Conclusions:

• The SEAD panel significantly enhances genetic imputation accuracy for Asian populations.
• The SEAD panel facilitates the discovery of ancestry-specific genetic variants, such as those influencing bone mineral density.
• Rare variants near SNTG1 may play a role in regulating bone mineral density through SNTG1 expression.