The Soifua Manuia reference panel with 2,570 Samoan haplotypes improves genotype imputation quality among Samoans

Genotype imputation is fundamental to association studies, and yet even gold standard panels like TOPMed are limited in the populations for which they yield good imputation. Specifically, Pacific Islanders are poorly represented in extant panels. To address this, we used whole-genome sequencing from 1,285 Samoan individuals combined with 1000 Genomes Project (1KGP) individuals to construct an imputation reference panel that better represents Pacific Islander, specifically Samoan, genetic variation. Here we show that this panel yielded up to two times more well-imputed (r2 ≥ 0.80) variants than TOPMed-R3 and 1KGP and was enriched for moderate and high impact variants. There was improved imputation accuracy across the minor allele frequency (MAF) spectrum; accuracy (r2) was greater for population-specific variants (high fixation index, FST) and those from larger haplotypes (high LD score). However, the gain in accuracy over TOPMed-R3 was largest for small haplotypes, reflecting the Samoan panel’s ability to capture variation not well tagged by other panels. A population-specific genotype imputation reference panel derived from whole-genome sequencing from 1,285 Samoan individuals outperforms existing reference panels.