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Timeline for releases:
Release
Date release to partners
Date release to public
Total sample size [1]
R2
Q4 2018 (Nov)
Q1 2020
​96,499​​
R3
Q2 2019 (May)
[1] samples used for PheWAS.
Q2 2020
135,638
R4
Q4 2019 (Oct)
Q4 2020
176,899
R5
Q2 2020 (March)
~Q2 2021
218,792
R6
Q3 2020
~Q3 2021
~274,000
R7
Q1 2021
~Q1 2022
~300,000
R8
Q3 2021
~Q3 2022
~340,000
R9
Q1 2022
~Q1 2023
~375,000
R10
Q3 2022
~Q3 2023
~410,000
R11
Q1 2023
~Q1 2024
~445,000
R12
Q3 2023
~Q3 2024
~480,000
R13
Q1 2024
~Q1 2025
~500,000
FinnGen a public-private partnership project combining genotype data from Finnish biobanks and digital health record data from Finnish health registries. FinnGen provides a unique opportunity to study genetic variation in relation to disease trajectories in an isolated population.
FinnGen is a growing project, aiming at 500,000 individuals in 2023.
FinnGen results are subjected to one year embargo and, after that, available to the larger scientific community via the Pheweb browser or through data download.
FinnGen individuals were genotyped with Illumina and Affymetrix chip arrays (Illumina Inc., San Diego, and Thermo Fisher Scientific, Santa Clara, CA, USA).
Chip genotype data were imputed using the population-specific SISu v3 imputation reference panel of 3,775 whole genomes.
Merged imputed genotype data is composed of 52 data sets that include samples from multiple cohorts.
Total number of individuals: 183,694
Total number of variants (merged set): 16,962,023
Reference assembly: GRCh38/hg38
Additionally to the biobanks mentioned in the previous releases, the following biobanks and cohorts are part of the R4 release:
To download FinnGen summary statistics you will need to fill the online form at this link. You will then receive an email containing the detailed instructions for downloading the data.
Release 4 contains
from
Please remember to acknowledge the FinnGen study when using these results in publications.
You can use the following text:
We want to acknowledge the participants and investigators of FinnGen study.
The Manifest file with the link to all the downloadable data is available at:
Please use the following description when referring to our project:
The FinnGen study is a large-scale genomics initiative that has analyzed over 500,000 Finnish biobank samples and correlated genetic variation with health data to understand disease mechanisms and predispositions. The project is a collaboration between research organisations and biobanks within Finland and international industry partners.
When using these results in publications, please remember to:
Acknowledge the FinnGen study. You can use the following text:
“We want to acknowledge the participants and investigators of the FinnGen study”
Cite our latest publication:
Kurki, M.I., Karjalainen, J., Palta, P. et al. FinnGen provides genetic insights from a well-phenotyped isolated population. Nature 613, 508–518 (2023). https://doi.org/10.1038/s41586-022-05473-8
Furthermore, if possible, include "FinnGen" as a keyword for your publication.
If you want to cite this website, use the following citation:
Genotype imputation was done with the population-specific .
Variant call set was produced with GATK HaplotypeCaller algorithm by following GATK best-practices for variant calling.
Genotype-, sample- and variant-wise QC was applied in an iterative manner by using the and the resulting high-quality WGS data for 3,775 individuals were phased with Eagle 2.3.5 as described in the previous section.
Genotype imputation was carried out by using the population-specific SISu v3 imputation reference panel with (version 08Jun17.d8b) as described in the following protocol: .
Post-imputation quality-control involved checking expected conformity of the imputation INFO-value distribution, MAF differences between the target dataset and the imputation reference panel and checking chromosomal continuity of the imputed genotype calls.
File naming pattern and file structure
GWAS summary statistics (tab-delimited, bgzipped, genome build 38, index files included) are named as {endpoint}.gz. For example, endpoint I9_CHD has I9_CHD.gz and I9_CHD.gz.tbi. Note that the results are based on imputed genotype data and produced using SAIGE and that is why the data is not presented as integers but might contain digits.
Chip genotype data processing and QC Samples were genotyped with Illumina (Illumina Inc., San Diego, CA, USA) and Affymetrix arrays (Thermo Fisher Scientific, Santa Clara, CA, USA).
Genotype calls were made with GenCall and zCall algorithms for Illumina and AxiomGT1 algorithm for Affymetrix data.
Chip genotyping data produced with previous chip platforms and reference genome builds were lifted over to build version 38 (GRCh38/hg38) following the protocol described here: .
v3 consists of 3,775 high coverage (30x) WGS Finnish individuals from six cohorts:
METSIM (PIs Markku Laakso and Mike Boehnke)
FINRISK (PI Pekka Jousilahti)
Cromwell-29 and 31
Wdltool-0.14
Plink 1.9 and 2.0
BCFtools 1.7 and 1.9
Eagle 2.3.5
Beagle 4.1 (version 08Jun17.d8b)
R 3.4.1 (packages: data.table 1.10.4, sm 2.2-5.4)
Prior imputation, chip genotyped samples were pre-phased with Eagle 2.3.5 with the default parameters, except the number of conditioning haplotypes was set to 20,000.
Finnish Migraine Family Study (PI Aarno Palotie)
Merck/Tienari samples (PI Pentti Tienari)
MESTA samples (PI Jaana Suvisaari)
High-coverage (25-30x) WGS data used to develop the SISu v3 reference panel were generated at the Broad Institute of MIT and Harvard and at the McDonnell Genome Institute at Washington University; and jointly processed at the Broad Institute.
@online{finngen,
author = {FinnGen},
title = {{FinnGen} Documentation of R4 release},
year = 2020,
url = {https://finngen.gitbook.io/documentation/},
urldate = {YYYY-MM-DD}
}number of samples: 3775
window size: 1500 kb
accuracy: low
number of threads: 96
LD threshold to include correlations: 0.05
LDstore v1.1 can be downloaded via:
And an example to extract variant range 20 Mb - 50 Mb from chromosome 7 is as follows:
wget http://www.christianbenner.com/ldstore_v1.1_x86_64.tgzldstore --bcor FG_LD_chr7.bcor --incl-range 20000000-50000000 --table output_file_name.tableTo learn more about the methods used, see section GWAS.
The {endpoint}.gz have the following structure:
Column name
Description
#chrom
chromosome on build GRCh38 (1-22, X)
pos
position in base pairs on build GRCh38
ref
reference allele
alt
alternative allele (effect allele)
rsids
variant identifier
Two fine-mapping methods were used:
Fine-mapping results are tab-delimited and bgzipped.
SuSiE results have the following filename pattern:
{endpoint}.SUSIE.cred.bgz
{endpoint}.SUSIE.snp.bgz
FINEMAP results have the following filename pattern:
{endpoint}.FINEMAP.region.bgz
{endpoint}.FINEMAP.snp.bgz
{endpoint}.FINEMAP.cred.bgz
To learn more about the methods used, see section fine-mapping.
SuSiE output files {endpoint}.SUSIE.snp.bgz have the following structure:
Column name
Description
trait
endpoint name
region
chr:start-end
v
variant identifier
rsid
rs variant identifier
chromosome
chromosome on build GRCh38 (1-22, X)
Linkage disequilibrium (LD) was estimated from SISU v3 for each chromosome. Use the tool LDstore (v1.1) for further usage of the bcor files.
ldstore --bcor FG_LD_chr1.bcor --incl-range 20000000-50000000 --table output_file_name.table
To learn more about the methods used, see section LD estimation.
The variant annotation has measures (HWE, INFO, ...) listed per batch.
To identify potential causal variants in GWAS signals, we fine-mapped each genome-wide significant (p < 5e-8) region from the 2,444 GWAS endpoints. Each region was fine-mapped with and . We used in-sample LD for fine-mapping.
We used a 3-megabase window (+- 1.5M) around each lead variant, merged overlapping regions into one, and used these regions for fine-mapping.
For matters related to this documentation, click Edit on GitHubor send us an email to finngen-info@helsinki.fi.
for the latest updates on the project as well as additional background information please consider visiting the study website or follow FinnGen on twitter .
If you want to host FinnGen summary statistics on your website, please get in contact with us at: humgen-servicedesk@helsinki.fi.
We used the (version 0.35.8.8) software for running the R4 GWAS.
is a mixed model logistic regression R/C++ package, able to account for related samples.
We analyzed:
​2,444 endpoints
For the null model computation for each endpoint, we used age, sex, 10 PCs and genotyping batch as covariates. Each genotyping batch was included as a covariate for an endpoint if there were at least 10 cases and 10 controls in that batch to avoid convergence issues. One genotyping batch need be excluded from covariates to not have them saturated. We excluded Thermo Fisher batch 16 as it was not enriched for any particular endpoints.
For calculating the genetic relationship matrix, we used the genotype dataset where genotypes with GP < 0.95 have been set missing. Only variants imputed with an INFO score > 0.95 in all batches were used. Variants with > 3 % missing genotypes were excluded as well as variants with MAF < 1 %. The remaining variants were LD pruned with a 1Mb window and r2 threshold of 0.1. This resulted in a set of 58,888 well-imputed not rare variants for GRM calculation.
SAIGE options for the null computation:
LOCO = false
numMarkers = 30
traceCVcutoff = 0.0025
ratioCVcutoff = 0.001
We ran association tests against each of the 2,444 endpoints with SAIGE for each variant with a minimum allele count of 5 from the imputation pipeline (SAIGE optionminMAC = 5). We filtered the results to include variants with an imputation INFO > 0.6.
nearest_genes
nearest gene name from variant
pval
p-value from SAIGE
beta
effect size estimated with SAIGE for the alternative allele
sebeta
standard deviation of effect size estimated with SAIGE
maf
alternative (effect) allele frequency
maf_cases
alternative (effect) allele frequency among cases
maf_controls
alternative (effect) allele frequency among controls
position
position in base pairs on build GRCh38
allele1
reference allele
allele2
alternative allele (effect allele)
maf
minor allele frequency
beta
effect size GWAS
se
standard error GWAS
p
p-value GWAS
mean
posterior expectation of true effect size
sd
posterior standard deviation of true effect size
prob
posterior probability of association
cs
identifier of 95% credible set (-1 = variant is not part of credible set)
16,962,023 variants
We included the following covariates in the model: sex, age, 10 PCs, genotyping batch.
The following filters were applied:
Exclusion of chromosome 23
Exclusion of variants with info score < 0.95
Exclusion of variants with missingness > 0.01 (based on the GP,see conversion)
Exclusion of variants with MAF < 0.05
LD pruning with window 500kb, step 50kb, r^2 filter of 0.1
This filtering step produced 36,944 variants, that were used for the rest of the analysis.
Then, FinnGen data was merged with the 1k genome project (1kgp) data, using the variants mentioned above. A round of PCA was performed and a bayesian algorithm was used to spot outliers. This process got rid of 4,686 outliers, of which 2,292 are from the FinnGen samples. The figure below shows the scatter plots for the first 3 PCs. Outliers, in red, are separated from the FinnGen blue cluster.
While the method automatically detected as being outliers the 1kgp samples with non European and southern European ancestries, it did not manage to exclude some samples with Western European origins. Since the signal from these sample would have been too small to allow a second round to be performed without detecting substructures of the Finnish population, another approach was used. The FinnGen samples that survived the first round were used to compute another PCA. The EUR and FIN 1kgp samples were then projected onto the space generated by the first 3 PCs. Then, the centroid of each cluster was calculated and used it to calculate the squared mahalanobis distance of each FinnGen sample to each of the centroids. Being the squared distance a sum of squared variables (with unitary variance, due to the mahalanobis distance), we could see it as a sum of 3 independent squared variables. This allowed to map the squared distance into a probability (chi squared with 3 degrees of freedom). Therefore, for each cluster, a probability of being part of it was computed. Then, a threshold of 0.95 was used to exclude FinnGen samples whose relative chance of being part of the Finnish cluster was below the level. This method produced another 588 outliers. The figure below shows the first three principal components.
FIN 1kgp samples are in purple, while EUR 1kgp sample are in Blue. Samples in green are FinnGen samples who are flagged as being non Finnish, while red ones are considered Finnish.
In a next step, all pairs of Finngen samples up to second degree were returned. The figure shows the distribution of kinship values.
Then, the previously defined “non Finnish” samples were excluded and 2 algorithms were used to return a unique subset of unrelated samples:
one called greedy would continuously remove the highest degree node from the network of relations, until no more links are left in the network.
one called native, based on a native implementation of python’s networkx package, performed on each subgraph of the network.
The largest independent set of either algorithm would be used to keep those sample, while flagging the others as “outliers” for the final PCA.
Then, the subset of outliers who also belong to the set of duplicates/twins was identified.
To compute the final step the Finngen samples were ultimately separated in three groups:
131,863 inliers: unrelated samples with Finnish ancestry.
46,916 outliers: non duplicate samples with Finnish ancestries, but who are also related to the inliers.
4,915 rejected samples: either of non Finnish ancestry or are twins/duplicates with relations to other samples.
Finally, the PCA for the inliers was calculated, and then outliers were projected on the same same, allowing to calculate covariates for a total of 178,779 samples.
Of the 178,779 non-duplicate population inlier samples from PCA, we excluded 1,880 samples from analysis because of missing minimum phenotype data or a mismatch between imputed sex and sex in registry data. ​A total of 176,899 samples was used for core analysis.
Documentation from the original developers of the algorithm can be found here: http://www.well.ox.ac.uk/~spencer/Aberrant/aberrant-manu.
The disease endpoints were defined using nationwide registries:
We harmonized over the International Classification of Diseases (ICD) revisions 8, 9 and 10, cancer-specific ICD-O-3, (NOMESCO) procedure codes, Finnish-specific Social Insurance Institute (KELA) drug reimbursement codes and ATC-codes.
These registries spanning decades were electronically linked to the cohort baseline data using the unique national personal identification numbers assigned to all Finnish citizens and residents.
A full list of FinnGen endpoints is for release 4.
The endpoints with fewer than 100 cases, near-duplicate endpoints, and developmental “helper” endpoints were excluded from the final PheWas (column “OMIT”).
Endpoints with N<150 are not released by (Finnish Institute for Health and Welfare).
(Risteys = intersection in Finnish) allows browsing of the FinnGen data at the phenotype level, including endpoint definitions, statistics about number of individuals, gender distribution, and longitudinal relationships.
