Dr. Taru Tukiainen is a senior researcher and a principal investigator at the Faculty of Medicine, University of Helsinki. She earned her D.Sc. (Tech.) degree in computational systems biology in 2012 and has extensive experience in human genomics, utilizing large-scale resources such as FinnGen in her research. Building on her landmark work on the human X chromosome inactivation (Nature, 2017), Taru established her own research group in 2018 focusing on the underpinnings of sex differences in health and disease. Her current research explores the genetic mechanisms and interactions that shape lifelong health, inluding sex-chromosomal effects, women’s health, and maternal-fetal interplay.
Genetic insights into the lifelong health of women and children
Epidemiological studies have established strong associations between various aspects of pregnancy – such as timing, number, and course – and the long-term health outcomes of both mothers and their children. For instance, earlier age at first birth (AFB) confers protection from breast cancer, and pregnancy complications associate with later-life disease burden in both the mother and the child.
Despite the public health implications of these associations, the mechanisms connecting pregnancy and reproduction to long-term health outcomes remain poorly understood. We work on closing this gap in our understanding through taking advantage of genotyped and detailed longitudinal healthcare information available from over the 500,000 Finns within the FinnGen study together with data from other Nordic biobanks.
We have compiled full reproductive histories of almost 200,000 FinnGen women (>45 years) from national healthcare records which facilitate our investigations of the potential etiological connections of reproductive trajectories and later-life health outcomes. Among these efforts we have investigated how reproductive choices and success, measured via AFB and lifetime parity, modulate the hereditary risk of breast cancer conferred by both polygenic risk and by single-gene pathogenic variants. We find that including AFB and parity in genetic risk prediction models of breast cancer allows for further stratification of high-risk individuals based on both polygenic and monogenic disease risk. Genetic analyses of AFB and parity in these women further confirm the largely independent etiologies of reproduction and breast cancer, while also highlighting new loci and both biological and behavioral correlates of AFB and parity.
Due to the large-scale sampling, FinnGen encompasses more than 95,000 parent-child relationships. We have been using this unique resource of family-based samples to dissect maternal-fetal interplay in pregnancy at the genetic level. Specifically, we apply Mendelian randomization in these data to investigate the causal mechanisms linking maternal health and lifestyle factors during pregnancy to child health outcomes. With this approach we have shown that the link between lower birthweight and later-life cardiometabolic disease risk is largely attributable to direct inheritance and genetic pleiotropy rather than resulting from intrauterine influences from the mother, as proposed by the DoHAD theory. We are currently investigating other maternal influences, including maternal hormonal levels, and their complex connections to the health of the children.