I'm interested in FinnGen rare variant phenotypes
The FinnGen project is fortunate to have >116k rare coding variants included, many of which are variants specific to the Finnish population bottleneck. The section Genotype Arrays Used describes the design and contents of the genotyping chip in more detail.
Variants
One advantage of FinnGen is that Finnish clinicians can use FinnGen to check variants they may have found in screening Finnish families to help determine if they are causative. Since these are Finnish-specific variants, they are often not found in more international resources such as ClinVar.
Variants can be classified by their frequency:
Common variant refers to variants > 1% and these will be most commonly found as imputed variants.
Low-frequency variant refers to variants with 0.1-1% frequency in the population. These are usually run on the chip but sometimes are common enough that they may also be imputed.
Rare variant usually refers to variants with <0.1% frequency in the population. These are usually available only in chip data.
(Ultra-rare variants are usually not present and FinnGen does not run gene-level burden tests such as SKAT-O. You can check Genebass for burden information of ultra-rare variants in UKBB, although this does not contain FinnGen data, it will give you an idea of the values in other populations.)
Available tools
Which tools are available depend on the frequency of the variant. Below is a map of tools.
Data availability:
Green boxes = green data access,
Red boxes = red-level Sandbox access.
More about Coding variant results including CHIP EWAS (Exome-Wide Association Scan) and Chip association browser https://dev2.finngen.fi/.
If you are interested in all the coding variants in a particular gene, you can go to PheWeb and then just type in the name of your gene. At the bottom, you will see all the imputed variants and any associations they may have to FinnGen phenotypes. Here is what is shown for TSHR:
Currently, to work with rarer variants you will need red-level Sandbox access.
How to work with rarer variants
Check genotyping quality via the Cluster Plots. (You can find all the cluster plots from the green library, but you will not be able to fix the calls or run a phenotypic analysis without red-level access.) Or use the Genotype Browser how to to view cluster plots and Rare Variant Calling in V3 to fix calls manually.
Look at your variant in the public resource Gnomad and check that it has been seen in Finland and what its allele frequency is. This can help you estimate if you have the correct number of heterozygotes (Finnish allele frequency from Gnomad v2 number of individuals in current data freeze = roughly the number of copies/hets for a rare or low frequency variant)
Run CodeWas with Cohort Operations tool to see which medical codes and FinnGen endpoints the variant is associated with. Use of Cohort Operations needs no coding skills. The other option to explore medical codes and FinnGen endpoints association is to run a PheWAS (see the section Variant PheWas and note also that we have a section on Interpreting rare-variant analysis results). Running PheWAS requires some experience with R programming.
See also General workflows for the most common analyses describing the most common workflows researchers are conducting in the Sandbox with the FinnGen. The methods described for genotype variant analysis suits also for exploring rare variants. These methods need no programming skills.
Using Sandbox requires red-level access.
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