Aarno Palotie, M.D., Ph.D.

1 500,000 individuals 2 10% of the population

Existing sample collections: 200,000 Finns

300,000 new sample donors within the coming 6 years FinnGen National Health Register data

3

500 000 individuals 500 000 individuals Combined ~1O % of the genotype and Association analyses population register data

Imputation

Axiom GWA array Public - Private Partnership 4

+2 new partners 5

331 000 participants

331 000 participants, so far 6 7 8 9 10

August 2019 data freeze 181 000 individuals Sandbox for Data Analysis, version 2

Approved users anywhere finngen.fi 11 in world Google Cloud Industry: Individual and group Abbvie Astra Zeneca workspaces Sandbox Celgene GSK Summary and count Merck/MSD level results for export, Sanofi download, portals Academic: UH, HUS, THL, Finnish Biobanks, standard or custom Sandbox Hospital Districts, Tools Universities in Finland or US, EU • Secure access to individual level data • Data cannot be copied 12

Success with from analyzing first 181,000 participants Data release 4 in numbers

13 • 181,821 individuals with genotypes and phenotypes

• 2,443 endpoints (n>100)

• Detailed longitudinal data in the Sandbox, 40 million drug purchases and ICD codes, 72 million health care events 14 Examples: New loci discovered based on the Finnish population structure Novel locus Mitja Kurki Juha Karjalainen15

MHC EMSY RNF186 MST1 UBAC2 FCGR2A NKX2-3 IL23R C1orf106 IL10 PheWas & Very consistent inflammatory association signal Fine Genomewide significant in Ankylosing Spondylitis, strong signal in UC/IBD and iridocyclitis Mapping

16 Type 2 diabetes 17512 cases, 114083 controls - >30 independent hits = Finnish-enriched low-frequency hits, not in Mahajan 2018

17

TCFL2

CCND2 CDKAL1 FTO

WFS1 MTNR1B IGF2BP2

IRS2 Missense variant Carrier frequency: 0.38 % Finland 0.25 % Estonia

0.012% in NW Europe 18 19 New analyses possible with lifelong medical data Expanded Phenotype Potential

20

Mean 340 health events per individual (including 186 drug purchases) Response to longterm use of common drugs

71,994 individuals have bought 21 statins at least once

statin # individuals simvastatin 56172 atorvastatin 36338 rosuvastatin 15038 fluvastatin 7957 pravastatin 5844 lovastatin 3221 cerivastatin 240 + Asthma and antibiotics use

22

no asthma

asthma Antibiotic Use Scan

Scan: Inverse rank normalized # purchases since 1995 Covariates: age, age2, sex, PCs, batches 23 Antibiotic Use Scan missense variant Previously characterized to Increase human rhinovirus C infection of ciliated cells 24 MHC

CDHR3 Longitudinal analyses

25 26 Can prediction have potential public health impact? Rare penetrant and common polygenic signal both assessed FinnGen arrays cover coding variation down to .01% frequency and offer complete coverage of disease alleles enriched through the founding bottleneck

27

CHEK2 frameshift PALB2 frameshift 1.7% carrier rate in Finland 0.3% carrier rate in Finland 28 Global Biobank Network Towards Global Partnership 29

Meta-analysis Biobank Meta-analysis Initiative > 2 million genotyped samples

Million Veteran Program deCODE Genetics 500k 250k

UK Biobank 30 Partners 500k Biobank 25k East London Genes & Health 36k Michigan Genome Initiative 47k HUNT Study 70k

Colorado Biobank FinnGen 180k 30k China Kadoorie Biobank 100k UCLA Precision Health Biobank Biobank Japan 14k BioME 200k 32k Estonian Biobank 150k BioVu 120k Mexico City

Generation LifeLines NL Scotland 52K *genotyped sample sizes 24k 3 1 Asthma

Biobank Japan BioMe-EA BioMe-AA BioMe-HA 8,204 cases, 10 loci 455 cases, 0 loci 842 cases, 0 loci 1,459 cases, 1 locus

31

China Kadoorie Biobank deCODE FinnGen Generation Scotland 990 cases, 0 loci 16,767 cases, 5 loci 15,926 cases, 14 loci 196 cases, 1 locus

HUNT Michigan Genomics Initiative UK Biobank 5,587 cases, 3 loci 6,079 cases, 0 loci 26,332 cases, 31 loci

Wei Zhou, Masa Kanai, Juha Karjalainen 3 2 Asthma

Biobank Japan BioMe-EA BioMe-AA BioMe-HA 8,204 cases, 10 loci 455 cases, 0 loci 842 cases, 0 loci 1,459 cases, 1 locus

Combined 32 82,837 cases, 82 loci

China Kadoorie Biobank deCODE FinnGen Generation Scotland 990 cases, 0 loci 16,767 cases, 5 loci 15,926 cases, 14 loci 196 cases, 1 locus

HUNT Michigan Genomics Initiative UK Biobank 5,587 cases, 3 loci 6,079 cases, 0 loci 26,332 cases, 31 loci

Wei Zhou, Masa Kanai, Juha Karjalainen Towards FinnGen 2

33 • FinnGen 2 scheduled to start in August 2020 • Industry partners should state if they are in or out in February • As there are new funding partners, FinnGen2 will expand its activities • -> pilots FinnGen Pilots

• Clinical data: FinnGen ejection fraction pilot (Aarno Palotie) 34 • Omics studies of Finnish alleles • Transcriptomics (Taru Tukiainen and Mark Daly) • Other omics??? (TBC) • Tumor data (Olli Carpen, Tomi Mäkelä) • Questionnaire study • LACONICS cognitive study (Andrea Ganna) • Baseline questionnaire and biobank portal (Markus Perola and FINBB) • Blood donors in FinnGen(Mikko Arvas) AcknowledgementsAcknowledgements