Systems epidemiology

The Systems Epidemiology laboratory at the Research Unit of Population Health is an internally and internationally actively collaborating group of around a dozen scientists in various career stages as identified below. For more information on the individual researchers, please follow the given links to the University Researcher Profiles.

Professors

Mika Ala-Korpela

Johannes Kettunen

Senior Researchers

Ville-Petteri Mäkinen

Minna K Karjalainen

Tuulia Tynkkynen

Eeva Sliz

Doctoral Researchers

Siyu Zhao

Tianqi Li

Marita Kalaoja

Andrei Ihanus

Anni Heikkilä

Ville Salo

The researchers in the Systems Epidemiology laboratory have published around 100 scientific papers over the last 5 years. Many of these publications have appeared in the leading journals of various fields. Representative examples are noted below for works led by the laboratory and for international collaborations.

KEY WORKS FROM THE LABORATORY

Sliz E, Tyrmi JS, Rahmioglu N, Zondervan KT, Becker CM; FinnGen; Uimari O, Kettunen J. Evidence of a causal effect of genetic tendency to gain muscle mass on uterine leiomyomata. Nat Commun. 2023 Feb 1;14(1):542. doi: 10.1038/s41467-023-35974-7. PMID: 36726022.

Mäkinen VP, Karsikas M, Kettunen J, Lehtimäki T, Kähönen M, Viikari J, Perola M, Salomaa V, Järvelin MR, Raitakari OT, Ala-Korpela M. Longitudinal profiling of metabolic ageing trends in two population cohorts of young adults. Int J Epidemiol. 2022 Dec 13;51(6):1970-1983. doi: 10.1093/ije/dyac062. PMID: 35441226.

Kuusisto S, Karjalainen MK, Tillin T, Kangas AJ, Holmes MV, Kähönen M, Lehtimäki T, Viikari J, Perola M, Chaturvedi N, Salomaa V, Raitakari OT, Järvelin MR, Kettunen J, Ala-Korpela M. Genetic and observational evidence: No independent role for cholesterol efflux over static high-density lipoprotein concentration measures in coronary heart disease risk assessment. J Intern Med. 2022 Jul;292(1):146-153. doi: 10.1111/joim.13479. Epub 2022 Mar 22. PMID: 35289444.

Ala-Korpela M, Zhao S, Järvelin MR, Mäkinen VP, Ohukainen P. Apt interpretation of comprehensive lipoprotein data in large-scale epidemiology: disclosure of fundamental structural and metabolic relationships. Int J Epidemiol. 2022 Jun 13;51(3):996-1011. doi: 10.1093/ije/dyab156. PMID: 34405869.

Ohukainen P, Virtanen JK, Ala-Korpela M. Vexed causal inferences in nutritional epidemiology-call for genetic help. Int J Epidemiol. 2022 Feb 18;51(1):6-15. doi: 10.1093/ije/dyab152. PMID: 34387668.

Sliz E, Huilaja L, Pasanen A, Laisk T, Reimann E, Mägi R; FinnGen; Estonian Biobank Research Team; Hannula-Jouppi K, Peltonen S, Salmi T, Koulu L, Tasanen K, Kettunen J. Uniting biobank resources reveals novel genetic pathways modulating susceptibility for atopic dermatitis. J Allergy Clin Immunol. 2022 Mar;149(3):1105-1112.e9. doi: 10.1016/j.jaci.2021.07.043. Epub 2021 Aug 27. PMID: 34454985.

Wang Q, Oliver-Williams C, Raitakari OT, Viikari J, Lehtimäki T, Kähönen M, Järvelin MR, Salomaa V, Perola M, Danesh J, Kettunen J, Butterworth AS, Holmes MV, Ala-Korpela M. Metabolic profiling of angiopoietin-like protein 3 and 4 inhibition: a drug-target Mendelian randomization analysis. Eur Heart J. 2021 Mar 21;42(12):1160-1169. doi: 10.1093/eurheartj/ehaa972. PMID: 33351885.

Ohukainen P, Kuusisto S, Kettunen J, Perola M, Järvelin MR, Mäkinen VP, Ala-Korpela M. Data-driven multivariate population subgrouping via lipoprotein phenotypes versus apolipoprotein B in the risk assessment of coronary heart disease. Atherosclerosis. 2020 Feb;294:10-15. doi: 10.1016/j.atherosclerosis.2019.12.009. Epub 2019 Dec 13. PMID: 31931463.

Kettunen J, Holmes MV, Allara E, Anufrieva O, Ohukainen P, Oliver-Williams C, Wang Q, Tillin T, Hughes AD, Kähönen M, Lehtimäki T, Viikari J, Raitakari OT, Salomaa V, Järvelin MR, Perola M, Davey Smith G, Chaturvedi N, Danesh J, Di Angelantonio E, Butterworth AS, Ala-Korpela M. Lipoprotein signatures of cholesteryl ester transfer protein and HMG-CoA reductase inhibition. PLoS Biol. 2019 Dec 20;17(12):e3000572. doi: 10.1371/journal.pbio.3000572. Erratum in: PLoS Biol. 2020 Mar 6;18(3):e3000694. PMID: 31860674.

Wang Q, Jokelainen J, Auvinen J, Puukka K, Keinänen-Kiukaanniemi S, Järvelin MR, Kettunen J, Mäkinen VP, Ala-Korpela M. Insulin resistance and systemic metabolic changes in oral glucose tolerance test in 5340 individuals: an interventional study. BMC Med. 2019 Nov 29;17(1):217. doi: 10.1186/s12916-019-1440-4. PMID: 31779625.

Tynkkynen T, Wang Q, Ekholm J, Anufrieva O, Ohukainen P, Vepsäläinen J, Männikkö M, Keinänen-Kiukaanniemi S, Holmes MV, Goodwin M, Ring S, Chambers JC, Kooner J, Järvelin MR, Kettunen J, Hill M, Davey Smith G, Ala-Korpela M. Proof of concept for quantitative urine NMR metabolomics pipeline for large-scale epidemiology and genetics. Int J Epidemiol. 2019 Jun 1;48(3):978-993. doi: 10.1093/ije/dyy287. PMID: 30689875.

Kuusisto S, Holmes MV, Ohukainen P, Kangas AJ, Karsikas M, Tiainen M, Perola M, Salomaa V, Kettunen J, Ala-Korpela M. Direct Estimation of HDL-Mediated Cholesterol Efflux Capacity from Serum. Clin Chem. 2019 Aug;65(8):1042-1050. doi: 10.1373/clinchem.2018.299222. Epub 2019 Apr 17. PMID: 30996052.

Sliz E, Kettunen J, Holmes MV, Williams CO, Boachie C, Wang Q, Männikkö M, Sebert S, Walters R, Lin K, Millwood LY, Clarke R, Li L, Rankin N, Welsh P, Delles C, Jukema JW, Trompet S, Ford I, Perola M, Salomaa V, Järvelin MR, Chen Z, Lawlor DA, Ala-Korpela M, Danesh J, Smith GD, Sattar N, Butterworth A, Würtz P. Metabolomic Consequences of Genetic Inhibition of PCSK9 Compared With Statin Treatment. Circulation. 2018 Nov 27;138(22):2499–2512. doi: 10.1161/CIRCULATIONAHA.118.034942. PMID: 30525347.

KEY COLLABORATIONS

Kurki MI, Karjalainen J, Palta P, Sipilä TP, Kristiansson K, Donner KM, Reeve MP, Laivuori H, Aavikko M, Kaunisto MA, Loukola A, Lahtela E, Mattsson H, Laiho P, Della Briotta Parolo P, Lehisto AA, Kanai M, Mars N, Rämö J, Kiiskinen T, Heyne HO, Veerapen K, Rüeger S, Lemmelä S, Zhou W, Ruotsalainen S, Pärn K, Hiekkalinna T, Koskelainen S, Paajanen T, Llorens V, Gracia-Tabuenca J, Siirtola H, Reis K, Elnahas AG, Sun B, Foley CN, Aalto-Setälä K, Alasoo K, Arvas M, Auro K, Biswas S, Bizaki-Vallaskangas A, Carpen O, Chen CY, Dada OA, Ding Z, Ehm MG, Eklund K, Färkkilä M, Finucane H, Ganna A, Ghazal A, Graham RR, Green EM, Hakanen A, Hautalahti M, Hedman ÅK, Hiltunen M, Hinttala R, Hovatta I, Hu X, Huertas-Vazquez A, Huilaja L, Hunkapiller J, Jacob H, Jensen JN, Joensuu H, John S, Julkunen V, Jung M, Junttila J, Kaarniranta K, Kähönen M, Kajanne R, Kallio L, Kälviäinen R, Kaprio J; FinnGen; Kerimov N, Kettunen J, Kilpeläinen E, Kilpi T, Klinger K, Kosma VM, Kuopio T, Kurra V, Laisk T, Laukkanen J, Lawless N, Liu A, Longerich S, Mägi R, Mäkelä J, Mäkitie A, Malarstig A, Mannermaa A, Maranville J, Matakidou A, Meretoja T, Mozaffari SV, Niemi MEK, Niemi M, Niiranen T, O Donnell CJ, Obeidat ME, Okafo G, Ollila HM, Palomäki A, Palotie T, Partanen J, Paul DS, Pelkonen M, Pendergrass RK, Petrovski S, Pitkäranta A, Platt A, Pulford D, Punkka E, Pussinen P, Raghavan N, Rahimov F, Rajpal D, Renaud NA, Riley-Gillis B, Rodosthenous R, Saarentaus E, Salminen A, Salminen E, Salomaa V, Schleutker J, Serpi R, Shen HY, Siegel R, Silander K, Siltanen S, Soini S, Soininen H, Sul JH, Tachmazidou I, Tasanen K, Tienari P, Toppila-Salmi S, Tukiainen T, Tuomi T, Turunen JA, Ulirsch JC, Vaura F, Virolainen P, Waring J, Waterworth D, Yang R, Nelis M, Reigo A, Metspalu A, Milani L, Esko T, Fox C, Havulinna AS, Perola M, Ripatti S, Jalanko A, Laitinen T, Mäkelä TP, Plenge R, McCarthy M, Runz H, Daly MJ, Palotie A. FinnGen provides genetic insights from a well-phenotyped isolated population. Nature. 2023 Jan;613(7944):508-518. doi: 10.1038/s41586-022-05473-8. Epub 2023 Jan 18. PMID: 36653562.

Luukkonen PK, Qadri S, Ahlholm N, Porthan K, Männistö V, Sammalkorpi H, Penttilä AK, Hakkarainen A, Lehtimäki TE, Gaggini M, Gastaldelli A, Ala-Korpela M, Orho-Melander M, Arola J, Juuti A, Pihlajamäki J, Hodson L, Yki-Järvinen H. Distinct contributions of metabolic dysfunction and genetic risk factors in the pathogenesis of non-alcoholic fatty liver disease. J Hepatol. 2022 Mar;76(3):526-535. doi: 10.1016/j.jhep.2021.10.013. Epub 2021 Oct 25. PMID: 34710482.

Auvinen J, Tapio J, Karhunen V, Kettunen J, Serpi R, Dimova EY, Gill D, Soininen P, Tammelin T, Mykkänen J, Puukka K, Kähönen M, Raitoharju E, Lehtimäki T, Ala-Korpela M, Raitakari OT, Keinänen-Kiukaanniemi S, Järvelin MR, Koivunen P. Systematic evaluation of the association between hemoglobin levels and metabolic profile implicates beneficial effects of hypoxia. Sci Adv. 2021 Jul 14;7(29):eabi4822. doi: 10.1126/sciadv.abi4822. PMID: 34261659.

Võsa U, Claringbould A, Westra HJ, Bonder MJ, Deelen P, Zeng B, Kirsten H, Saha A, Kreuzhuber R, Yazar S, Brugge H, Oelen R, de Vries DH, van der Wijst MGP, Kasela S, Pervjakova N, Alves I, Favé MJ, Agbessi M, Christiansen MW, Jansen R, Seppälä I, Tong L, Teumer A, Schramm K, Hemani G, Verlouw J, Yaghootkar H, Sönmez Flitman R, Brown A, Kukushkina V, Kalnapenkis A, Rüeger S, Porcu E, Kronberg J, Kettunen J, Lee B, Zhang F, Qi T, Hernandez JA, Arindrarto W, Beutner F; BIOS Consortium; i2QTL Consortium; Dmitrieva J, Elansary M, Fairfax BP, Georges M, Heijmans BT, Hewitt AW, Kähönen M, Kim Y, Knight JC, Kovacs P, Krohn K, Li S, Loeffler M, Marigorta UM, Mei H, Momozawa Y, Müller-Nurasyid M, Nauck M, Nivard MG, Penninx BWJH, Pritchard JK, Raitakari OT, Rotzschke O, Slagboom EP, Stehouwer CDA, Stumvoll M, Sullivan P, 't Hoen PAC, Thiery J, Tönjes A, van Dongen J, van Iterson M, Veldink JH, Völker U, Warmerdam R, Wijmenga C, Swertz M, Andiappan A, Montgomery GW, Ripatti S, Perola M, Kutalik Z, Dermitzakis E, Bergmann S, Frayling T, van Meurs J, Prokisch H, Ahsan H, Pierce BL, Lehtimäki T, Boomsma DI, Psaty BM, Gharib SA, Awadalla P, Milani L, Ouwehand WH, Downes K, Stegle O, Battle A, Visscher PM, Yang J, Scholz M, Powell J, Gibson G, Esko T, Franke L. Large-scale cis- and trans-eQTL analyses identify thousands of genetic loci and polygenic scores that regulate blood gene expression. Nat Genet. 2021 Sep;53(9):1300-1310. doi: 10.1038/s41588-021-00913-z. Epub 2021 Sep 2. PMID: 34475573.

Robinson O, Carter AR, Ala-Korpela M, Casas JP, Chaturvedi N, Engmann J, Howe LD, Hughes AD, Järvelin MR, Kähönen M, Karhunen V, Kuh D, Shah T, Ben-Shlomo Y, Sofat R, Lau CE, Lehtimäki T, Menon U, Raitakari O, Ryan A, Providencia R, Smith S, Taylor J, Tillin T, Viikari J, Wong A, Hingorani AD, Kivimäki M, Vineis P. Metabolic profiles of socio-economic position: a multi-cohort analysis. Int J Epidemiol. 2021 Jul 9;50(3):768-782. doi: 10.1093/ije/dyaa188. PMID: 33221853.

Richardson TG, Wang Q, Sanderson E, Mahajan A, McCarthy MI, Frayling TM, Ala-Korpela M, Sniderman A, Smith GD, Holmes MV. Effects of apolipoprotein B on lifespan and risks of major diseases including type 2 diabetes: a mendelian randomisation analysis using outcomes in first-degree relatives. Lancet Healthy Longev. 2021 Jun;2(6):e317-e326. doi: 10.1016/S2666-7568(21)00086-6. Epub 2021 May 21. PMID: 34729547.

Karpale M, Käräjämäki AJ, Kummu O, Gylling H, Hyötyläinen T, Orešič M, Tolonen A, Hautajärvi H, Savolainen MJ, Ala-Korpela M, Hukkanen J, Hakkola J. Activation of pregnane X receptor induces atherogenic lipids and PCSK9 by a SREBP2-mediated mechanism. Br J Pharmacol. 2021 Jun;178(12):2461-2481. doi: 10.1111/bph.15433. Epub 2021 May 14. PMID: 33687065.

Gomez-Alonso MDC, Kretschmer A, Wilson R, Pfeiffer L, Karhunen V, Seppälä I, Zhang W, Mittelstraß K, Wahl S, Matias-Garcia PR, Prokisch H, Horn S, Meitinger T, Serrano-Garcia LR, Sebert S, Raitakari O, Loh M, Rathmann W, Müller-Nurasyid M, Herder C, Roden M, Hurme M, Jarvelin MR, Ala-Korpela M, Kooner JS, Peters A, Lehtimäki T, Chambers JC, Gieger C, Kettunen J, Waldenberger M. DNA methylation and lipid metabolism: an EWAS of 226 metabolic measures. Clin Epigenetics. 2021 Jan 7;13(1):7. doi: 10.1186/s13148-020-00957-8. PMID: 33413638.

Vojinovic D, Kalaoja M, Trompet S, Fischer K, Shipley MJ, Li S, Havulinna AS, Perola M, Salomaa V, Yang Q, Sattar N, Jousilahti P, Amin N, Satizabal CL, Taba N, Sabayan B, Vasan RS, Ikram MA, Stott DJ, Ala-Korpela M, Jukema JW, Seshadri S, Kettunen J, Kivimaki M, Esko T, van Duijn CM. Association of circulating metabolites in plasma or serum and risk of stroke: Meta-analysis from seven prospective cohorts. Neurology. 2020 Dec 2;96(8):e1110–23. doi: 10.1212/WNL.0000000000011236. Epub ahead of print. PMID: 33268560.

Folkersen L, Gustafsson S, Wang Q, Hansen DH, Hedman ÅK, Schork A, Page K, Zhernakova DV, Wu Y, Peters J, Eriksson N, Bergen SE, Boutin TS, Bretherick AD, Enroth S, Kalnapenkis A, Gådin JR, Suur BE, Chen Y, Matic L, Gale JD, Lee J, Zhang W, Quazi A, Ala-Korpela M, Choi SH, Claringbould A, Danesh J, Davey Smith G, de Masi F, Elmståhl S, Engström G, Fauman E, Fernandez C, Franke L, Franks PW, Giedraitis V, Haley C, Hamsten A, Ingason A, Johansson Å, Joshi PK, Lind L, Lindgren CM, Lubitz S, Palmer T, Macdonald-Dunlop E, Magnusson M, Melander O, Michaelsson K, Morris AP, Mägi R, Nagle MW, Nilsson PM, Nilsson J, Orho-Melander M, Polasek O, Prins B, Pålsson E, Qi T, Sjögren M, Sundström J, Surendran P, Võsa U, Werge T, Wernersson R, Westra HJ, Yang J, Zhernakova A, Ärnlöv J, Fu J, Smith JG, Esko T, Hayward C, Gyllensten U, Landen M, Siegbahn A, Wilson JF, Wallentin L, Butterworth AS, Holmes MV, Ingelsson E, Mälarstig A. Genomic and drug target evaluation of 90 cardiovascular proteins in 30,931 individuals. Nat Metab. 2020 Oct;2(10):1135-1148. doi: 10.1038/s42255-020-00287-2. Epub 2020 Oct 16. PMID: 33067605.

Richardson TG, Sanderson E, Palmer TM, Ala-Korpela M, Ference BA, Davey Smith G, Holmes MV. Evaluating the relationship between circulating lipoprotein lipids and apolipoproteins with risk of coronary heart disease: A multivariable Mendelian randomisation analysis. PLoS Med. 2020 Mar 23;17(3):e1003062. doi: 10.1371/journal.pmed.1003062. PMID: 32203549.

Gallois A, Mefford J, Ko A, Vaysse A, Julienne H, Ala-Korpela M, Laakso M, Zaitlen N, Pajukanta P, Aschard H. A comprehensive study of metabolite genetics reveals strong pleiotropy and heterogeneity across time and context. Nat Commun. 2019 Oct 21;10(1):4788. doi: 10.1038/s41467-019-12703-7. PMID: 31636271.

Deelen J, Kettunen J, Fischer K, van der Spek A, Trompet S, Kastenmüller G, Boyd A, Zierer J, van den Akker EB, Ala-Korpela M, Amin N, Demirkan A, Ghanbari M, van Heemst D, Ikram MA, van Klinken JB, Mooijaart SP, Peters A, Salomaa V, Sattar N, Spector TD, Tiemeier H, Verhoeven A, Waldenberger M, Würtz P, Davey Smith G, Metspalu A, Perola M, Menni C, Geleijnse JM, Drenos F, Beekman M, Jukema JW, van Duijn CM, Slagboom PE. A metabolic profile of all-cause mortality risk identified in an observational study of 44,168 individuals. Nat Commun. 2019 Aug 20;10(1):3346. doi: 10.1038/s41467-019-11311-9. PMID: 31431621.

Locke AE, Steinberg KM, Chiang CWK, Service SK, Havulinna AS, Stell L, Pirinen M, Abel HJ, Chiang CC, Fulton RS, Jackson AU, Kang CJ, Kanchi KL, Koboldt DC, Larson DE, Nelson J, Nicholas TJ, Pietilä A, Ramensky V, Ray D, Scott LJ, Stringham HM, Vangipurapu J, Welch R, Yajnik P, Yin X, Eriksson JG, Ala-Korpela M, Järvelin MR, Männikkö M, Laivuori H; FinnGen Project; Dutcher SK, Stitziel NO, Wilson RK, Hall IM, Sabatti C, Palotie A, Salomaa V, Laakso M, Ripatti S, Boehnke M, Freimer NB. Exome sequencing of Finnish isolates enhances rare-variant association power. Nature. 2019 Aug;572(7769):323-328. doi: 10.1038/s41586-019-1457-z. Epub 2019 Jul 31. Erratum in: Nature. 2019 Nov;575(7783):E4. PMID: 31367044.

Lea A, Subramaniam M, Ko A, Lehtimäki T, Raitoharju E, Kähönen M, Seppälä I, Mononen N, Raitakari OT, Ala-Korpela M, Pajukanta P, Zaitlen N, Ayroles JF. Genetic and environmental perturbations lead to regulatory decoherence. Elife. 2019 Mar 5;8:e40538. doi: 10.7554/eLife.40538. PMID: 30834892.

SHORT RESEARCH COMMUNICATIONS AND EDITORIALS

Li T, Ihanus A, Ohukainen P, Järvelin MR, Kettunen J, Mäkinen VP, Tynkkynen T, Ala-Korpela M. There is always glucose in normal urine: unspecific excretion associated with serum glucose and glomerular filtration rate. Int J Epidemiol. 2022 Dec 13;51(6):2022-2025. doi: 10.1093/ije/dyac060. PMID: 35373831.

Ala-Korpela M, Kuusisto S, Holmes MV. Commentary: Big data bring big controversies: HDL cholesterol and mortality. Int J Epidemiol. 2021 Jul 9;50(3):913-915. doi: 10.1093/ije/dyab016. PMID: 33604617.

Kuusisto S, Kostara C, Kangas AJ, Perola M, Salomaa V, Kettunen J, Ala-Korpela M. HDL-Mediated Cholesterol Efflux Associates with Incident Kidney Disease. Clin Chem. 2021 Mar 31;67(4):689-691. doi: 10.1093/clinchem/hvab024. PMID: 33723592.

Ala-Korpela M, Holmes MV. Polygenic risk scores and the prediction of common diseases. Int J Epidemiol. 2020 Feb 1;49(1):1-3. doi: 10.1093/ije/dyz254. PMID: 31828333.

Ala-Korpela M. The culprit is the carrier, not the loads: cholesterol, triglycerides and apolipoprotein B in atherosclerosis and coronary heart disease. Int J Epidemiol. 2019 Oct 1;48(5):1389-1392. doi: 10.1093/ije/dyz068. PMID: 30968109.

Holmes MV, Ala-Korpela M. What is 'LDL cholesterol'? Nat Rev Cardiol. 2019 Apr;16(4):197-198. doi: 10.1038/s41569-019-0157-6. PMID: 30700860.

Ala-Korpela M. Objective Metabolomics Research. Clin Chem. 2018 Jan;64(1):30-33. doi: 10.1373/clinchem.2017.274852. Epub 2017 Oct 16. PMID: 29038155.