> For the complete documentation index, see [llms.txt](https://help.connected.illumina.com/llms.txt). Markdown versions of documentation pages are available by appending `.md` to page URLs; this page is available as [Markdown](https://help.connected.illumina.com/annotation/v3.27/data-sources/topmed.md).

# TOPMed

### Overview

The [Trans-Omics for Precision Medicine](https://www.nhlbi.nih.gov/science/trans-omics-precision-medicine-topmed-program) (TOPMed) program, sponsored by the National Institutes of Health (NIH) National Heart, Lung and Blood Institute (NHLBI), is part of a broader Precision Medicine Initiative, which aims to provide disease treatments tailored to an individual’s unique genes and environment. TOPMed contributes to this Initiative through the integration of whole-genome sequencing (WGS) and other omics (e.g., metabolic profiles, epigenomics, protein and RNA expression patterns) data with molecular, behavioral, imaging, environmental, and clinical data.

{% hint style="info" %}
**Publication**

Kowalski, M.H., Qian, H., Hou, Z., Rosen, J.D., Tapia, A.L., Shan, Y., Jain, D., Argos, M., Arnett, D.K., Avery, C. and Barnes, K.C., 2019. Use of> 100,000 NHLBI Trans-Omics for Precision Medicine (TOPMed) Consortium whole genome sequences improves imputation quality and detection of rare variant associations in admixed African and Hispanic/Latino populations. *PLoS genetics*, **15(12)**, p.e1008500.
{% endhint %}

### VCF extraction

We currently extract the following fields from TOPMed VCF file:

```scss
##INFO=<ID=AN,Number=1,Type=Integer,Description="Number of Alleles in Samples with Coverage">
##INFO=<ID=AC,Number=A,Type=Integer,Description="Alternate Allele Counts in Samples with Coverage">
##INFO=<ID=AF,Number=A,Type=Float,Description="Alternate Allele Frequencies">
##INFO=<ID=Het,Number=A,Type=Integer,Description="Number of samples with heterozygous genotype calls">
##INFO=<ID=Hom,Number=A,Type=Integer,Description="Number of samples with homozygous alternate genotype calls">
```

Example:

```scss
chr1    10132   TOPMed_freeze_5?chr1:10,132     T       C       255     SVM     VRT=1;NS=62784;AN=125568;AC=32;AF=0.000254842;Het=32;Hom=0      NA:FRQ  125568:0.000254842
```

### GRCh37 liftover

The data is not available for GRCh37 on TOPMed website. We performed a liftover from GRCh38 to GRCh37 using dbSNP ids.

### Download URL

<https://bravo.sph.umich.edu/freeze5/hg38/download>

### JSON output

```json
"topmed":{ 
   "allAc":20,
   "allAn":125568,
   "allAf":0.000159,
   "allHc":0,
   "failedFilter":true
}
```

| Field        | Type  | Notes                                                                |
| ------------ | ----- | -------------------------------------------------------------------- |
| allAc        | int   | TOPMed allele count                                                  |
| allAn        | int   | TOPMed allele number. Non-zero integer.                              |
| allAf        | float | TOPMed allele frequency (computed by Illumina Connected Annotations) |
| allHc        | int   | TOPMed homozygous count                                              |
| failedFilter | bool  | True if this variant failed any filters                              |


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