Epigenomics of Complex Traits
Our group studies the role of genetics and the environment in epigenetic processes, and how these processes relate to the development of common diseases and complex traits. We study twins from the Finnish Twin Cohort Study allowing various study designs to assess the contribution of genetics vs environment in epigenetic processes. Our group aims to produce reliable trait biomarkers, and potential risk predictors for common diseases, and to understand the phenomenon of aging.
Obesity and mitochondrial function
Epigenetic modifiers use metabolites as cofactors that are either directly produced within mitochondria, or their production is indirectly affected by metabolic pathways within mitochondria. Mitochondrial function is necessary for the epigenetic makeup of nuclear DNA, which regulates chromatin function including the expression of genes encoding mitochondrial proteins.
We hypothesize that impaired mitochondrial biogenesis result in alterations to nuclear DNAme and whole body metabolic maladaptation in obesity, as well as in accelerated aging. Importantly, these epigenetic effects may be reversible.
Aging and lifestyle
Ever-increasing human lifespan has put aging at the center of public health policies worldwide, yet we lack a clear understanding of why and how we grow old. Although chronological age correlates with various age-related diseases and conditions, biological age provides better information about overall health and indicates how rapidly a person is aging. We study biological aging, and how various lifestyles and risk factors affect the rate of biological aging. We use epigenetic clocks, which are the most promising predictors of biological aging.
We hypothesize that higher reproductive investment may lead to accelerated biological aging and a reduced healthspan. Also, exposures and conditions during early life and puberty may accelerate aging and have long-term effects of health in later life.
Collaborations
We actively collaborate nationally and internationally, and participate in large international consortia, such as inGenetics of DNA methylation Consortium and in large scale EWAS studies on cannabis use, major depressive disorder, antidepressant use, and ADHD to name a few.
Selected publications
Sehovic, E, Zellers SM, Youssef MK, Heikkinen A, Kaprio J, Ollikainen M. DNA methylation sites in early adulthood characterised by pubertal timing and development: a twin study. Clinical Epigenetics 2023, 15:181 https://doi.org/10.1186/s13148-023-01594-7
Föhr T, Waller K, Viljanen A, Rantanen T, Kaprio J, Ollikainen M, and Sillanpää E. Mortality Associations With DNA Methylation-Based Biological Aging and Physical Functioning Measures Across a 20-Year Follow-up Period. Gerontol A Biol Sci Med Sci, Advance Access publication January 22, 2023 https://doi.org/10.1093/gerona/glad026
Lapatto HAK, Kuusela M, Heikkinen A, Muniandy M, van der Kolk BW, Gopalakrishnan S, Pöllänen N, Sandvik M, Schmidt MS, Heinonen S, Saari S, Kuula J, Hakkarainen A, Tampio J, Saarinen T, Taskinen M-R, Lundbom N, Groop P-H, Tiirola M, Katajisto P, Lehtonen M, Brenner C, Kaprio J, Pekkala S#, Ollikainen M#, Pietiläinen KHP* and Pirinen E*. Nicotinamide riboside improves muscle mitochondrial biogenesis, satellite cell differentiation and gut microbiota in a twin study. Science Advances 2023, 9; 2 DOI: 10.1126/sciadv.add5163
Kankaanpää, A, Tolvanen, A, Heikkinen, A, Kaprio, J, Ollikainen, M, Sillanpää, E The role of adolescent lifestyle habits in biological aging: A prospective twin study eLIFE 2022, Nov 8 https://doiorg/107554/eLife80729
Marttila S, Tamminen H, Rajić S, Mishra PP, Lehtimäki T, Raitakari O, Kähönen M, Kananen L, Jylhävä J, Hägg S, Delerue T, Peters A, Waldenberger M, Kleber ME, März W, Luoto R, Raitanen J, Sillanpää E, Laakkonen EK, Heikkinen A, Ollikainen M, Raitoharju E Methylation status of VTRNA2-1/nc886 is stable across populations, monozygotic twin pairs and in majority of tissues Epigenomics, 2022, 14(18) https://doi.org/10.2217/epi-2022-0228
Bode HF, Heikkinen A, Lundgren S, Kaprio J, Ollikainen M. Differences in DNA Methylation-Based Age Prediction Within Twin Pairs Discordant for Cancer. Twin Res Hum Genet 2022 25;4-5 DOI: https://doi.org/10.1017/thg.2022.32
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
Drouard G, Ollikainen M, Mykkänen J, Raitakari O, Lehtimäki T, Kähönen M, Mishra PP, Wang X, Kaprio J. Multi-Omics Integration in a Twin Cohort and Predictive Modeling of Blood Pressure Values OMICS: A Journal of Integrative Biology, 26(3), 130-141 https://doiorg/101089/omi20210201
Kankaanpää A, Tolvanen A, Saikkonen P, Heikkinen A, Laakkonen EK, Kaprio J, Ollikainen M, Sillanpää E. Do epigenetic clocks provide explanations for sex differences in lifespan? A cross-sectional twin study J Gerontol A Biol Sci Med Sci 2022 Sep 1;77(9):1898-1906 doi:101093/gerona/glab337
van Dongen J, Gordon SD, McRae AF, Odintsova VV, Mbarek h, Breeze CE, Sugden K, Lundgren S, Castillo-Fernandez JE, Hannon E, Moffitt TE, Hagenbeek FA, van Beijsterveldt CEM, Hottenga JJ, Tsai PC, BIOS Consortium*, Genetics of DNA Methylation Consortium*, Min JL, Hemani G, Ehli EA, Paul F, Stern CD, Heijmans BT Slagboom PE, Daxinger L, van der Maarel SM, de Geus EJC, Willemsen G, Montgomery GW, Reversade B, Ollikainen M, Kaprio J, Spector TD, Bell JT, Mill J, Caspi A, Martin NG & Boomsma DI Identical twins carry a persistent epigenetic signature of early genome programming Nature Communications, 2021 12, 5618 https://doiorg/101038/s41467-021-25583-7
External funding
Eemil Aaltosen säätiö (Mikaela Hukkanen)
Sigrid Jusélius Foundation
Medicinska understödsföreningen Liv och Hälsa r.f.
Minerva Foundation
MSCA-ITN CANCERPREV (Hannes Bode)