On this page, you will find summaries of the latest dissertations from Folkhälsan Research Center, providing insights into recent research. Further down, you will also find a comprehensive list of past dissertations, including links to the full texts.
Genetics and metabolomics of cardiovascular disease in type 1 diabetes
Anni Antikainen: This thesis suggests that both genetics and metabolomics bear potential to improve cardiovascular disease prediction – and could hence provide clinical utility in type 1 diabetes.
Anni Antikainen: Genetics and metabolomics of cardiovascular disease in type 1 diabetes
People with diabetes carry an elevated risk of cardiovascular disease, but the genetics of cardiovascular disease has not been much studied in diabetes, especially not in type 1 diabetes.
In this doctoral thesis, millions of genetic variants were tested for an association with coronary artery disease in persons with type 1 diabetes. A well-established risk locus, CDKN2B-AS1, was found to be associated with coronary artery disease also in type 1 diabetes. A novel genetic risk variant was discovered near DEFB127, which however still await external replication. A genetic risk score, built with 156 established coronary artery disease risk variants, was found capable of improving prediction of up-coming coronary artery disease from clinical risk factors. Millions of rare genetic variants were also evaluated for an association with stroke in type 1 diabetes. The burden of protein altering variants was suggested to be associated with stroke on ANK1, LRRN1, UACA, and HAS1; although, still awaiting external replication.
In this doctoral thesis, the urinary metabolome was evaluated with respect to coronary artery disease in type 1 diabetes. For instance, urinary xanthosine was found to associate with up-coming coronary artery disease. Overall, the urinary metabolome was found capable of improving prediction of up-coming coronary artery disease from the clinical risk factors on a shorter follow-up period.
To conclude, this thesis suggests that both genetics and metabolomics bear potential to improve cardiovascular disease prediction – and could hence provide clinical utility in type 1 diabetes.
Genetic and metabolomic factors of type 1 diabetes and diabetic kidney disease
Jani Haukka: Our results showed that a significant proportion of individuals with type 1 diabetes retain C-peptide, and thus insulin production, even years or decades after the diabetes onset.
Jani Haukka: Genetic and metabolomic factors of type 1 diabetes and diabetic kidney disease
Type 1 diabetes and its complication, diabetic kidney disease, are severe and complex conditions. Type 1 diabetes affects over 8 million individuals worldwide, while diabetic kidney disease is the leading cause of end-stage kidney disease in developed countries. Although the understanding of the aetiology of type 1 diabetes, as well as the genetic and metabolomic background of diabetic kidney disease, has improved greatly in recent years, much remains unknown.
My PhD thesis aimed to study the presence of residual insulin production in individuals with type 1 diabetes, measured by serum C-peptide concentrations, and to investigate genetic and metabolomic background of diabetic kidney disease.
Our results showed that a significant proportion of individuals with type 1 diabetes retain C-peptide, and thus insulin production, even years or decades after the diabetes onset. Those with an older age at onset and a lower type 1 diabetes polygenic risk score were more likely to retain C-peptide production. The C-peptide concentrations were also associated with a lower risk of diabetic complications.
We also identified serum metabolites associated with increased risk of diabetic kidney disease, including N-trimethyl-5-aminovalerate and the artificial sweetener erythritol. The most significant genetic findings included the LTA gene, which is involved in inflammation regulation, and CCSER1 gene.
Genetic predisposition to uveal melanoma in the Finnish population
Pauliina Repo: The study highlights the importance of BAP1 and expands the possibility that uveal melanoma may be part of broader cancer syndromes in some individuals.
Pauliina Repo: Genetic predisposition to uveal melanoma in the Finnish population
This thesis explored genetic factors that may contribute to the risk of developing uveal melanoma (UM), the most common eye cancer in adults, with a focus on the Finnish population, where uveal melanoma incidence is among the highest in the world.
Particular attention was given to the BAP1 gene, a known uveal melanoma risk gene. The study confirmed that ~2% of all patients and 25% of those with familial uveal melanoma carried pathogenic BAP1 variants, including two potential Finnish founder mutations.
Other known cancer risk genes – such as BRCA1, MET, CHEK2, DDX41, FANCM, HOXB13, RAD50, SDHA, and SDHB – were occasionally found to harbor pathogenic or likely pathogenic variants. However, no strong evidence supported the involvement of the MBD4 gene, another suggested uveal melanoma risk gene, in uveal melanoma predisposition in the Finnish population.
Overall, the study highlights the importance of BAP1 and expands the possibility that uveal melanoma may be part of broader cancer syndromes in some individuals.
Novel disease mechanisms and effects of gene therapy in mouse models of neonatal mitochondrial complex III deficiency
Rishi Banerjee: This research offers hope for future treatments of GRACILE syndrome and similar mitochondrial diseases, suggesting that even if only one organ can be treated, significant health improvements are possible.
Rishi Banerjee: Novel disease mechanisms and effects of gene therapy in mouse models of neonatal mitochondrial complex III deficiency
GRACILE syndrome is a severe genetic disease affecting newborns. The disease disrupts the body's ability to produce energy, affecting multiple organs and early death.
This study focused on using gene therapy, a technique that introduces healthy copies of genes into cells to fix problems. In experiments with mice that have GRACILE syndrome, researchers found that targeting the liver with gene therapy could dramatically improve the animals' health. The treated mice lived longer, maintained normal body temperatures, and had better control over their blood sugar levels.
One surprising finding was the role of the liver in regulating body temperature. Normally, tissues like brown fat and muscle help keep the body warm, but in the sick mice, these tissues weren't working properly. After gene therapy, the liver metabolism was able to produce enough heat to keep the mice warm, showing that fixing the energy production of the liver can compensate when other systems fail.
This research offers hope for future treatments of GRACILE syndrome and similar mitochondrial diseases, suggesting that even if only one organ can be treated, significant health improvements are possible.
Cerebral small vessel disease and stroke in type 1 diabetes – The impact of blood pressure, haptoglobin genotype, and diabetic retinopathy
Marika Eriksson: The results suggest that cerebrovascular disease in type 1 diabetes is linked to microvascular damage and that the health of the eye’s blood vessels may reflect the health of the brain’s blood vessels.
Marika Eriksson: Cerebral small vessel disease and stroke in type 1 diabetes – The impact of blood pressure, haptoglobin genotype, and diabetic retinopathy
Cerebrovascular disease, such as stroke, is a severe complication of type 1 diabetes, with a high risk of disability and mortality. It is not fully clear how cerebrovascular complications develop, but diabetes is suggested to damage the brain’s small vessels similarly to other diabetic microvascular damage.
This study aimed to assess factors associated with early signs of cerebrovascular brain damage in asymptomatic individuals with type 1 diabetes, as well as risk markers for the development of stroke in these individuals.
Our results showed that cerebral small vessel disease is associated with elevated nocturnal blood pressure in type 1 diabetes. We also found cerebral small vessel diseases to be more common with increasing severity of diabetic eye disease and that severe diabetic eye disease marked an increased risk of having a stroke.
The results suggest that cerebrovascular disease in type 1 diabetes is linked to microvascular damage and that the health of the eye’s blood vessels may reflect the health of the brain’s blood vessels.
Sleep habits of Finnish preschoolers: Associations with diet and weight
Anna Abdollahi: Children with a later chronotype at preschool age were associated with greater weight gain over the eight-year follow-up period.
Frailty and functioning as determinants of healthcare use
Jenni Ikonen: We found that frailty was associated with greater specialized and primary healthcare service use. Furthermore, frailty and its faster progression rate were associated with increased medical imaging service use and costs.
Estrogen biosynthesis in subcutaneous and visceral adipose tissue in women
Natalia Hetemäki: We found that considerable amounts of estrogens were produced in fat already before menopause. After menopause, the role of visceral adipose tissue in the production of estrogens was highlighted.
Genetic and Functional Studies of Ultra-Rare Diseases
Johanna Lehtonen: A striking binding pattern was unraveled: the ends of the nebulin super-repeat region bound strongly to filamentous actin, whereas the central part bound weakly.
Feline personality and problematic behaviour – Associations with demographic, genetic, and environmental factors
Salla Mikkola: The most important factors associating with the problematic behaviour were cat's breed and personality traits, especially fearfulness and sociability.
Biomarkers of the Gut Fungal and Bacterial Composition in Inflammatory Bowel Disease
Rebecka Ventin-Holmberg: The results showed that treatment responses could be accurately predicted even before treatment initiation, and that gut microbiota health improved during successful treatment.
Simple devices for single-cell trapping and droplet digital PCR
Pinja Elomaa: The study presents promising advancements in droplet technology, offering cost-efficient and fast solutions for single-cell capturing and nucleic acid amplification, with potential future commercial applications in various settings, from field laboratories to clinical facilities.
Growth, puberty, gynecological health, and fertility in women with APECED
Viivi Saari: We showed that subjects with APECED have progressive growth impairment through prepuberty until the attainment of adult height.
Cardiometabolic health and morbidity in offspring of women with type 1 diabetes
Cedric Korpijaakko: The findings from this thesis suggest that exposure to type 1 diabetes during fetal development might affect long-term health in offspring.
List of dissertations
Anna Abdollahi: Sleep habits of Finnish preschoolers: Associations with diet and weight
Having a later chronotype often increases the risk of circadian misalignment, as social demands often conflict with internal biological clocks. Among adolescents and adults, a later chronotype has been associated with less healthy sleep patterns, poorer diet quality, increased weight status, and reduced overall well-being. However, little research has focused on younger children, leaving it unclear when these associations begin to develop.
Using data from the DAGIS project, we employed novel, data-driven sleep estimation methods with actigraphy data to assess several sleep measures, including chronotype.
While children with a later chronotype were not associated with higher weight outcomes during preschool age, they were associated with less healthy diet quality, including lower vegetable and higher sugary food consumption. Furthermore, children with a later chronotype at preschool age were associated with greater weight gain over the eight-year follow-up period.
In conclusion, our findings suggest that preschool age may be a critical period when children vulnerable to circadian misalignment potentially begin to experience its negative effects. More research is needed to understand sleep, diet, and weight trajectories in children and the early role of circadian misalignment in weight development.
My dissertation also explored the associations between other sleep measures (duration, timing, quality) with diet (energy intake, macronutrient intake, and food consumption), and weight outcomes.
Anna Abdollahi: 2025.
Jenni Ikonen: Frailty and functioning as determinants of healthcare use
The aging global population is creating new demands for healthcare systems. Understanding factors that drive healthcare use is essential for planning preventative measures and adapting the services to meet the needs of the aging populations. Frailty, characterized by vulnerability to stressors and impaired recovery, is proposed to explain health differences among older adults, while maintaining functioning is central to healthy aging. Therefore, we aimed to investigate whether frailty and functioning would be associated with healthcare use.We found that frailty was associated with greater specialized and primary healthcare service use. Furthermore, frailty and its faster progression rate were associated with increased medical imaging service use and costs. Participants with poorer physical functioning had higher utilization rates of specialized healthcare services compared to participants with better functioning. Poorer mental functioning, in turn, was associated with a higher number of first outpatient visits. In conclusion, public health interventions should be considered to prevent frailty and support functioning among aging populations.
Jenni Ikonen: 2024.
Natalia Hetemäki: Estrogen biosynthesis in subcutaneous and visceral adipose tissue in women
Adipose tissue, or fat tissue, is important in the production of sex steroids like estrogens and androgens, especially after menopause. The distribution of adipose tissue in women changes over the course of their reproductive life – at menopause, the relative amount of visceral compared to subcutaneous adipose tissue increases, and this leads to an increased risk of metabolic disorders such as cardiovascular disease and type of 2 diabetes. Menopausal hormone therapy seems to mitigate these changes.
We studied changes taking place in the biosynthesis of estrogens in subcutaneous and visceral adipose tissue in women before and after menopause. We also studied how the production of estrogens and androgens in fat is affected by the use of menopausal hormone therapy.
We found that considerable amounts of estrogens were produced in fat already before menopause. After menopause, the role of visceral adipose tissue in the production of estrogens was highlighted. Users of menopausal hormone therapy had high tissue to serum concentrations of estrogens and increased local estrogen-to-androgen ratios in adipose tissue compared to women without hormone therapy. These changes could play a role in the preventive effect that menopausal hormone therapy has on menopause-associated visceral adiposity.
Natalia Hetemäki: 2024.
Johanna Lehtonen: Genetic and Functional Studies of Ultra-Rare Diseases
In my doctoral thesis, I investigated the genetic inheritance of ultra-rare diseases in twelve families using different high-throughput sequencing (HTS) methods. Of those methods, a technology called linked-read sequencing was studied in more detail.
The study showed that linked-read sequencing can solve the haplotype information (in other words, the information which set of variants are inherited from each parent) even for very large muscle disease genes if the DNA meets quality standards.
These different sequencing strategies resulted in identifying a molecular genetic diagnosis in four families when variants in ACTA1, CCDC88A, MYH3, and TPM3 genes were identified. The thesis work also included functional laboratory studies: the disease-causing mechanisms of the identified CCDC88A variants were evaluated using patient cells.
Additionally, the binding ability of wild-type nebulin and actin muscle sarcomere proteins was investigated. A striking binding pattern was unraveled: the ends of the nebulin super-repeat region bound strongly to filamentous actin, whereas the central part bound weakly.
Johanna Lehtonen: . 2024.
Salla Mikkola: Feline personality and problematic behaviour – Associations with demographic, genetic, and environmental factors
Like dogs, cats can have problematic behaviour. Problematic behaviour is an important subject to study as it can decrease the welfare of both the owner and the cat. We targeted four common problems in cats and studied which demographical, personality and environmental factors associate with them. In addition, we investigated the structure of personality in cats and validated the data with multiple methods.
The results show that the problematic behaviours are complex and affected by various variables. The most important factors associating with the problematic behaviour were cat's breed and personality traits, especially fearfulness and sociability. The gathered data was proven to be valid and reliable.
Salla Mikkola: . 2024.
Rebecka Ventin-Holmberg: Biomarkers of the Gut Fungal and Bacterial Composition in Inflammatory Bowel Disease
Research on biomarkers of the gut microbiota may support the important development of precision and personalization of treatment and indication of disease predisposition. Here biomarkers to predict inflammatory bowel disease treatment response were examined and inflammatory-linked biomarkers were investigated from the fungal microbiota of antibiotic-treated infants.
The results showed that treatment responses could be accurately predicted even before treatment initiation, and that gut microbiota health improved during successful treatment. Additionally, significant changes were observed in the fungal gut microbiota of infants exposed to antibiotics.
Rebecka Ventin-Holmberg: . 2024.
Pinja Elomaa: Simple devices for single-cell trapping and droplet digital PCR
Droplet technology holds immense potential in various biomedical applications, from single-cell techniques to ddPCR, wherein samples are compartmentalized into numerous droplets housing individual cells or RNA/DNA strands.
Despite existing advanced devices, many are costly and complex. This study focused on advancing droplet-based systems for biomedical research and diagnostics, aiming to develop accessible and portable chips suitable for rapid diagnostics.
Experimental results demonstrate efficacious isolation of single cells as well as isolation and amplification of RNA strands within droplets, particularly showcasing efficient nucleic acid amplification of the SARS-CoV-2 virus using the isothermal amplification reaction, SIBA (Aidian).
Overall, the study presents promising advancements in droplet technology, offering cost-efficient and fast solutions for single-cell capturing and nucleic acid amplification, with potential future commercial applications in various settings, from field laboratories to clinical facilities.
Pinja Elomaa: . 2024.
Viivi Saari: Growth, puberty, gynecological health, and fertility in women with APECED
Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) is a rare genetic disorder arising from mutations in the autoimmune regulator (AIRE) gene.
AIRE participates in the regulation of autoimmunity. Clinical presentation of APECED is variable, with over 20 different disease manifestations recognized. In women, primary ovarian insufficiency is one of the most common endocrine manifestations.
Our primary objectives were to investigate growth patterns of patients with APECED from birth until the attainment of adult height and to explore effects of APECED on pubertal development, sexual health, and fertility in women with APECED.
We showed that subjects with APECED have progressive growth impairment through prepuberty until the attainment of adult height. Primary ovarian insufficiency often develops shortly after puberty leading to sex hormone deficiencies and a decline in fertility.
Pregnancies in women with APECED are rare, but pregnancy outcomes are usually favourable for both the mother and the infant.
Viivi Saari:. 2024.
Cedric Korpijaakko: Cardiometabolic health and morbidity in offspring of women with type 1 diabetes
It has been suggested that exposure to maternal diabetes in utero may program the development of cardiometabolic diseases in offspring during adulthood.
The aim of this doctoral thesis was to assess whether maternal type 1 diabetes affects cardiometabolic health in offspring, by investigating prescription drug purchases and by evaluating clinical signs of cardiometabolic diseases during young adulthood.
From the age of seven, we observed that offspring of women with type 1 diabetes purchased significantly more prescription drugs for several indications than offspring of women without diabetes, with increased purchases of prescription drugs used in the treatment of diabetes and cardiovascular disease.
We could not find any differences between offspring of women with type 1 diabetes and offspring of women without diabetes for anthropometric measures or glucose or lipid concentrations in young adulthood.
A new finding was increased arterial stiffness in young adult offspring of women with type 1 diabetes compared to offspring of women without diabetes, while other metrics of cardiovascular disease remained similar.
The findings from this thesis suggest that exposure to type 1 diabetes during fetal development might affect long-term health in offspring.
