Description
This track shows allele frequencies for 672,843 variants from the
Taiwan
Precision Medicine Initiative (TPMI), a large cohort of people of
Han Chinese ancestry recruited in Taiwan. The frequencies come from the
publicly released annotation of the Axiom TPM1 SNP array, the
population-optimized chip that TPMI used to genotype 165,596 of its
participants. Variants are positioned on hg38 (GRCh38). About 80% of
the sites are biallelic SNVs; the remainder are short insertions or
deletions and a small number of multi-nucleotide variants.
TPMI is one of the largest non-European cohorts in genetic research,
with 565,390 enrolled participants as of the v37 data freeze. Han
Chinese people are nearly 20% of the world's population but are
under-represented in genetic studies. A cohort of this size is useful
for population-specific allele frequency reference, GWAS replication,
and clinical variant interpretation in East Asian populations.
Display
The track uses the standard UCSC VCF display. Hovering a variant shows
the cohort allele frequency (AF), the derived allele count
(AC), the assumed total allele number (AN), the TPMI
NGS concordance score from the chip annotation, and the Affymetrix
probe set ID.
Methods
TPMI participants were recruited from 16 partner medical centres (33
affiliated hospitals) across Taiwan, who together serve about 40% of the
Taiwanese population. Each participant donated a blood sample and
consented to access of their electronic medical records. Genomic DNA
was extracted with the QIAsymphony DSP DNA Mini Kit and genotyped on
two custom Axiom arrays (TPMv1 and TPMv2; Thermo Fisher Scientific)
designed to optimally tag Han Chinese variation. Genotype calling was
done with Applied Biosystems Array Power Tools using the Best Practices
Workflow at the National Center for Genome Medicine, Academia Sinica.
After QC, the TPMv1 array had been used on 165,596 participants and
TPMv2 on 321,360 (486,956 with both genotype and EMR). The cohort has
broad coverage of Han Chinese subgroups as well as Indigenous Taiwanese
populations. See the TPMI Nature paper (in References) for sample
recruitment, calling, imputation and quality control details.
The source data for this track is the Axiom TPM1 chip annotation file
TPM1_Array_Annotation.csv distributed by Thermo Fisher
Scientific (create date 2022-06-01), which embeds the TPMI cohort allele
frequency in a column named Allele Frequency alongside the
probe-design metadata. The chip annotation declares hg38 coordinates,
so no liftover was needed. We converted the CSV to VCF with the script
tpmiToVcf.py:
rows on alt or random contigs were dropped, rows flagged as TPMI
blacklist or with no reported allele frequency were dropped, and indels
encoded with - for the empty allele were rewritten in
VCF-compatible form by prepending an anchor base read from the hg38
reference with twoBitToFa. The resulting VCF was sorted and
indexed with bcftools sort and tabix. The full
recipe is in the
makeDoc
file.
The source publishes only allele frequencies, not allele counts. To
make the track usable in count-based aggregate views, we derived
AC = round(AF * AN) with AN = 100,000. This AN value
was chosen because every reported AF in the file is an exact integer
multiple of 1/100,000, so the source data was rounded to that
precision. The TPMv1 chip was used on 165,596 participants (~330,000
chromosomes for autosomes), so the true AN may be roughly three times
larger; the AC values published here are therefore proportional to the
true counts but not equal to them. The assumption is documented in the
VCF header.
Caveats
Of 752,921 rows in the source CSV, 672,843 were emitted to the VCF.
The skipped rows are: 80,034 rows with no reported allele frequency
(the chip carries probe annotations for some sites that the TPMI cohort
did not type or quality-filter, including the entire chrY content of
the chip); 36 rows on alt or random contigs; 8 rows with no defined
reference allele in the source. About 61,000 rows are also flagged as
TPMI blacklist; none of those have a published allele frequency, so
they are filtered out by the no-AF rule.
The TPM2 chip annotation (~755,000 SNPs) is not represented in this
track because its public annotation does not embed a TPMI cohort allele
frequency column. It only carries the 1000 Genomes / HapMap CEU/CHB/JPT/YRI
frequencies that ship with all Affymetrix Axiom chips, which are already
available through dbSNP. About 234,255 SNPs are shared between TPM1 and
TPM2, so the TPM1-only track still covers most of the cohort-typed
content.
The TPMI authors note that allele frequencies on the TPMv1 chip are
reliable for variants with MAF above about 0.1%; rarer sites are
reported but should be interpreted cautiously because SNP arrays have
higher genotyping error at low MAF.
Data Access
Due to license restrictions, the data for this track cannot be downloaded from the UCSC
Genome Browser. The Table Browser, Data Integrator, and download server are not available
for this track.
The original Axiom TPM1 chip annotation CSV is distributed by Thermo Fisher Scientific;
search their support site for "Axiom TPM1 Annotation" to download the matching version
(we used the 2022-06-01 release).
Credits
Thanks to the TPMI participants and to the Academia Sinica and Thermo
Fisher Scientific teams that designed and curated the Axiom TPMv1 SNP
array and published the chip annotation file.
References
Yang HC, Kwok PY, Li LH, Liu YM, Jong YJ, Lee KY, Wang DW, Tsai MF, Yang JH, Chen CH et al.
The Taiwan Precision Medicine Initiative provides a cohort for large-scale studies.
Nature. 2025 Dec;648(8092):117-127.
PMID: 41092961; PMC: PMC12675286