A whole-genome reference panel of 14,393 individuals for East Asian populations accelerates discovery of rare functional variants

Underrepresentation of non-European populations hinders growth of global
precision medicine. Resources such as imputation reference panels that
match the study population are necessary to find low-frequency variants
with substantial effects. We created a reference panel consisting of
14,393 whole-genome sequences including more than 11,000 Asian
individuals. Genome-wide association studies were conducted using the
reference panel and a population-specific genotype array of 72K subjects
for eight phenotypes. This panel yields improved imputation accuracy of
rare and low-frequency variants within East Asian populations compared
with the largest reference panel. Thirty-nine previously unidentified
associations were found, and more than half of the variants were
East-Asian-specific. We discovered genes with rare protein-altering
variants, including LTBP1 for height and GPR75 for body mass index, as
well as putative regulatory mechanisms for rare noncoding variants with
cell-type-specific effects. We suggest this data set will add to the
potential value of Asian precision medicine.