Epigenomics of Complex Traits

We combine genetics, epigenetics, proteomics, metabolomics, and other cutting-edge omics technologies with detailed lifestyle and health data to uncover the biological mechanisms that shape long-term health trajectories. Our work integrates large-scale population studies, including the Finnish Twin Cohort, FinnGen, the UK Biobank, and clinical intervention studies, creating a unique framework for understanding how genes, environment, and behavior interact across the lifespan.

We focus on understanding healthy and unhealthy obesity, since not all obesity is the same. Individuals with similar body weight can have remarkably different health outcomes. Our goal is to identify the molecular and genetic factors that distinguish high-risk obesity from metabolically healthy obesity.

We develop advanced genetic and multi-omics approaches to predict individual health risks, identify biological pathways underlying obesity-related diseases, and understand why some individuals are more resilient to excess adiposity than others. A unique aspect of our work is the use of evolutionary biology as a framework for understanding obesity and metabolic health. By studying both human populations and animal models, including wild and captive King penguins, we investigate whether metabolic resilience reflects evolutionary adaptation to energy storage and environmental change.

Mitochondria, the energy-producing organelles within our cells, play a central role in metabolism, aging, and health. We investigate why some individuals experience mitochondrial decline that accelerates aging and hinders long-term weight management, while others maintain healthier cellular function throughout life.

Using genetically informative study designs, intervention studies, and molecular analyses, we aim to uncover the causal pathways linking mitochondrial dysfunction, obesity, and biological aging. We study how genetic variation, lifestyle factors, and epigenetic regulation influence mitochondrial health and determine responses to interventions such as weight loss treatments and mitochondrial-targeted therapies.

A major goal of our research is to translate biological discoveries into practical tools for personalized medicine and public health. By integrating multi-omics data with advanced biological aging biomarkers, including epigenetic and proteomic clocks, we seek to identify individuals at greatest risk of premature aging and obesity-related disease before clinical symptoms emerge.

Ultimately, our vision is to enable more precise prevention, improve healthy life expectancy, and support healthier aging across the population.

Selected publications

Heikkinen A, Uusitalo-Kylmälä L, Blom I, Helge JW, Gillberg L, Seaborne R, Larsen S, Jacques M, Grolaux R, Aaltonen S, Kaprio J, van der Kolk BW, Heinonen S, Eynon N, Pietiläinen KH, Kivelä R, Pirinen E, Ollikainen M. The divergent effects of nicotinamide riboside and high-intensity exercise training on skeletal muscle epigenetic aging. Aging Cell 2026, accepted for publication

Zhu T, Faragó T, Bollepalli S, Heikkinen A, Hukkanen M, Raitakari O, … Ollikainen M. EpiSmokEr2: a robust epigenetic classifier for smoking status inference using Illumina EPIC methylation data. Epigenomics, 1–11. https://doi.org/10.1080/17501911.2026.2630841

Drouard G, Argentieri MA, Heikkinen A, Ollikainen M, Kaprio J. Associations between 40-year trajectories of BMI and proteomic and epigenetic aging clocks: deciphering nonlinearity and interactions. Aging Cell 2026, 25(2), e70397. https://doi.org/10.1111/acel.70397

Cristofari R, Davis L, Bardon G, Fernandes F, Figueroa ME, Franzenburg S, Gauthier-Clerc M, Grande F, Heidrich R, Hukkanen M, Le Maho Y, Ollikainen M, Paciello E, Rampal P, Stenseth NC, Trucchi E, Zahn S, Le Bohec C, Meyer BS. Lifestyle change accelerates epigenetic ageing in King penguins. Nat Commun 2026 17, 3795. https://doi.org/10.1038/s41467-026-70527-8

Hukkanen M, Kankaanpää A, Heikkinen A, Kaprio J, Cristofari R, Ollikainen M. Epigenetic aging and lifespan reflect reproductive history in the Finnish Twin Cohort. Nat Commun 2026 Jan 8;17(1):44. doi: 10.1038/s41467-025-67798-y

Kuo C, Liu P, Drouard G, Vuoksimaa E, Kaprio J, Ollikainen M, Chen Z, Pilling LC, Atkins JL, Fortinsky RH, Kuchel GA, Diniz BS. A proteomic signature of healthspan. Proc. Natl. Acad. Sci. U.S.A. 2025 122;23 e2414086122, https://doi.org/10.1073/pnas.2414086122

Drouard G, Suhonen S, Heikkinen A, Wang Z, Kaprio J, Ollikainen M. Multi-Omic Associations of Epigenetic Age Acceleration Are Heterogeneously Shaped by Genetic and Environmental Influences. Aging Cell 2025 May 5 https://doi.org/10.1111/acel.70088

Heikkinen A, Esser VFC, Lundgren S, Lee SHT, Hakkarainen A, Lundbom J, Kuula J, Groop P-H, Heinonen S, Pajukanta P, Kaprio J, Pietiläinen KH, Li S, Ollikainen M. Twin pair analysis uncovers links between DNA methylation, mitochondrial DNA quantity and obesity. Nat Commun 2025 16;4374 https://doi.org/10.1038/s41467-025-59576-7

Drouard G, Wang Z, Heikkinen A, Foraster M, Julvez J, Kanninen KM, van Kamp I, Pirinen M, Ollikainen M, Kaprio J. Lifestyle differences between co-twins are associated with decreased similarity in their internal and external exposome profiles. Scientific Rep 2024;14:21261 https://doi.org/10.1038/s41598-024-72354-7

Lundgren S, Kuitunen S, Pietiläinen K, Hurme M, Kähönen M, Mannistö S, Perola M, Lehtimäki T, Raitakari O, Kaprio J, Ollikainen M. BMI is positively associated with accelerated epigenetic aging in twin pairs discordant for BMI Journal of Internal Medicine, 2022, June 14 https://doiorg/101111/joim13528

External funding

Sigrid Jusélius Foundation
Medicinska understödsföreningen Liv och Hälsa r.f.
Minerva Foundation
University of Helsinki, Doctoral Program in Population Helath and Behavior, Doctoral Education Pilot in Precision Cancer Medicine, and the Research Foundation
HiLIFE Joint Postdoc Funds
Finnish Cultural Foundation
Kymenlaakso Fund
Juho Vainio Foundation

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ResearchGate: Miina Ollikainen