Timo Antero Lakka

• MD, PhD
• Professor at University of Eastern Finland

Background Cardiovascular diseases (CVDs) are the leading cause of morbidity and premature mortality globally. While the relationship between indicators of physical fitness and arterial structure and stiffness are reasonably well-studied in adults, these associations in children and adolescents remain less understood. The aim of this study was to i...

Studies on longitudinal associations between diet quality and lipid and amino acid metabolism in children and adolescents are limited. We studied associations between diet quality and serum markers of lipid and amino acid metabolism in the Physical Activity and Nutrition in Children (PANIC) study. These analyses included 403 children aged 6–9 years...

Objective The aim of this study was to conduct a longitudinal investigation of the associations between changes in dietary factors and changes in caries experience among Finnish children and adolescents participating in the Physical Activity and Nutrition in Children (PANIC) study. Methods Among 487 children included at baseline at the age of 6 to...

Importance Mental health problems often arise during adolescence and early adulthood, affecting up to 25% to 30% of young people. Enhancing the ability to identify children and adolescents at increased risk of mental health problems and uncover factors that promote mental health from childhood to adolescence is important. Objective To investigate...

Complete characterization of the genetic effects on gene expression is needed to elucidate tissue biology and the etiology of complex traits. In the present study, we analyzed 2,344 subcutaneous adipose tissue samples and identified 34,774 conditionally distinct expression quantitative trait locus (eQTL) signals at 18,476 genes. Over half of eQTL g...

Introduction Non-communicable diseases are the leading causes of premature mortality worldwide. Both genetic predispositions and environmental exposures affect disease risk. Biobanks have increased understanding of genetic predictors of these diseases, but environmental influences are expected to be larger. Individuals also create their own environ...

Background Our aim was to assess the relationships of cardiovascular health metrics, cardiorespiratory fitness, lean mass, and fat percentage with arterial structure and function from childhood to adolescence. Methods and Results Five hundred four children aged 6 to 9 years were examined in the PANIC (Physical Activity and Nutrition in Children) s...

Background Cognitive and mental health problems are highly prevalent in adolescence. While higher levels of physical fitness may mitigate these problems, there is a lack of long-term follow-up studies on the associations of physical fitness from childhood with cognition and mental health in adolescence. Objective We investigated the associations o...

We performed large-scale genome-wide gene-sleep interaction analyses of lipid levels to identify novel genetic variants underpinning the biomolecular pathways of sleep-associated lipid disturbances and to suggest possible druggable targets. We collected data from 55 cohorts with a combined sample size of 732,564 participants (87% European ancestry)...

Objective: To evaluate the ability of near-infrared light transillumination (NIR-LT) to detect interproximal enamel and dentinal caries lesions compared to clinical-visual inspection (VI) aided by fibre-optic transillumination (FOTI). Method and materials: From 170 Finnish adolescents aged 15-17 years, 5294 interproximal surfaces of premolars an...

Environmental and lifestyle factors, including air pollution, impaired diet, and low physical activity, have been associated with cardiometabolic risk factors in childhood and adolescence. However, environmental and lifestyle exposures do not exert their physiological effects in isolation. This study investigated associations between an exposome sc...

Skeletal muscle, the largest human organ by weight, is relevant to several polygenic metabolic traits and diseases including type 2 diabetes (T2D). Identifying genetic mechanisms underlying these traits requires pinpointing the relevant cell types, regulatory elements, target genes, and causal variants. Here, we used genetic multiplexing to generat...

Chromatin accessibility quantitative trait loci (caQTL) discovery is vital for linking epigenomic features with genetic variations in Type 2 diabetes (T2D). However, caQTL scans require clear epigenomic signals, posing challenges in rare cell types from single nucleus (sn) studies. To address this, we proposed using deep learning (DL) to upscale ch...

Mechanisms of insulin action differ between fasting and postprandial states across tissues, with postprandial disturbance in insulin action being crucial in the development of type 2 diabetes (T2D). We generated single nucleus (sn-) chromatin accessibility and transcriptome profiles of 287 skeletal muscle biopsies from the FUSION Tissue Biopsy Stud...

Aim Higher adiposity and increased risk of cardiovascular diseases have been reported in juvenile idiopathic arthritis (JIA), but body composition measurements have produced inconsistent results. This controlled cross‐sectional study assessed body composition with two methods to evaluate adiposity in children with JIA. Methods We measured body com...

Long-term lifestyle interventions in childhood and adolescence can significantly improve cardiometabolic health, but the underlying molecular mechanisms remain poorly understood. To address this knowledge gap, we conducted an 8-year diet and physical activity intervention in a general population of children. The research revealed that the intervent...

Background Cardiovascular diseases (CVDs) are the leading cause of morbidity and premature mortality globally. While the relationship between indicators of physical fitness and arterial health is reasonably well-studied in adults, these associations in children and adolescents remain less understood. The aim of this study was to investigate longitu...

We investigated the associations of the measures of arterial health with cognition in adolescents and whether physical activity (PA) or sedentary time (ST) confounds these associations. One hundred sixteen adolescents (71 boys) aged 15.9 ± 0.4 participated in the study. PA and ST were assessed using a combined accelerometer/heart rate monitor. Over...

Objective We investigated the longitudinal associations of cumulative motor fitness, muscular strength, and cardiorespiratory fitness (CRF) from childhood to adolescence with cortical excitability and inhibition in adolescence. The other objective was to determine cross-sectional associations of motor fitness and muscular strength with brain functi...

Objectives Prior studies on the psychological well‐being in pediatric inflammatory bowel disease (PIBD) have reported controversial results. Our aim was to compare the psychological well‐being and lifestyle factors in patients with PIBD and their controls and to assess the role of contributing disease characteristics. Methods This cross‐sectional...

Background: Molecular mechanisms underlying the beneficial effects of long-term lifestyle interventions on cardiometabolic health during childhood and adolescence remain largely unknown. Such information would provide valuable insights into the prevention of cardiometabolic diseases since childhood. We therefore studied for the first time the effec...

Although both short and long sleep duration are associated with elevated hypertension risk, our understanding of their interplay with biological pathways governing blood pressure remains limited. To address this, we carried out genome-wide cross-population gene-by-short-sleep and long-sleep duration interaction analyses for three blood pressure tra...

Cardiovascular and mental diseases are among the most important global health problems, but little is known on the associations between mental and arterial health in adolescents. Therefore, we investigated the associations of arterial health with depressive symptoms and perceived stress in adolescents. A total of 277 adolescents, 151 boys, 126 girl...

Background Increased physical activity (PA) may mitigate the negative cardiovascular health effects of sedentary behavior in adolescents. However, the relationship of PA and sedentary time from childhood with cardiac function in adolescence remains underexplored. Therefore, we investigated the associations of cumulative sedentary time and PA from c...

Although both short and long sleep duration are associated with elevated hypertension risk, our understanding of their interplay with biological pathways governing blood pressure remains limited. To address this, we carried out genome-wide cross-population gene-by-short-sleep and long-sleep duration interaction analyses for three blood pressure tra...

Introduction Due to a steep increase in obesity, metabolic dysfunction‐associated fatty liver disease (MAFLD) has also become the most common chronic hepatic condition among children and adolescents. Various maternal and pregnancy‐related factors have also been implicated in the development of MAFLD, but human studies remain scarce. Material and m...

Context Small birth size and increased postnatal growth have been associated with earlier timing of adrenarche and puberty, but it is not well known whether these factors alone or together lead to earlier maturation. Objective This work aimed to search for different growth trajectories using a clustering approach to analyze the effects of birth si...

Scope: Various lifestyle and sociodemographic factors have been associated with risk factors for type 2 diabetes (T2D). However, their combined associations with T2D risk factors have been studied much less. Materials and results: This study investigates cross-sectional associations of lifestyle patterns with T2D risk factors among 2925 adults a...

Background Prenatal urban environmental exposures have been associated with blood pressure in children. The dynamic of these associations across childhood and later ages is unknown. Objectives The purpose of this study was to assess associations of prenatal urban environmental exposures with blood pressure trajectories from childhood to early adul...

Background This study aimed to assess whether moderate-to-vigorous physical activity (MVPA), sport and exercise as a proxy measure of muscle and bone strengthening activity, sedentary behaviour, and sleep were associated with total-body-less-head (TBLH) bone mineral content (BMC) and TBLH lean mass cross-sectionally and longitudinally from age 6 to...

Purpose To investigate the associations of overall diet quality and dietary factors with serum biomarkers for lipid and amino acid metabolism in a general population of children. Methods We studied 194 girls and 209 boys aged 6–8 years participating in the Physical Activity and Nutrition in Children study. Food consumption was assessed by 4-day fo...

Skeletal muscle, the largest human organ by weight, is relevant to several polygenic metabolic traits and diseases including type 2 diabetes (T2D). Identifying genetic mechanisms underlying these traits requires pinpointing the relevant cell types, regulatory elements, target genes, and causal variants. Here, we used genetic multiplexing to generat...

Objectives and Study The often‐recommended alanine aminotransferase (ALT) cutoffs (girls 21 U/l, boys 25 U/l) are based on a NHANES cohort. A novel concept of metabolic dysfunction associated steatotic liver disease (MASLD) emphasizes the role of ALT. We tested the prevalence of increased ALT and MASLD in children with overweight or obesity applyin...

Introduction: Educational attainment, widely used in epidemiologic studies as a surrogate for socioeconomic status, is a predictor of cardiovascular health outcomes. Methods: A two-stage genome-wide meta-analysis of low-density lipoprotein cholesterol (LDL), high-density lipoprotein cholesterol (HDL), and triglyceride (TG) levels was performed whil...

Background Genome-wide association studies for glycemic traits have identified hundreds of loci associated with these biomarkers of glucose homeostasis. Despite this success, the challenge remains to link variant associations to genes, and underlying biological pathways. Methods To identify coding variant associations which may pinpoint effector ge...

Introduction Mental health disorders are increasing worldwide, leading to significant personal, economic, and social consequences. Mental health promotion and prevention have been the subject of many systematic reviews. Thus, decision makers likely face the problem of going through literature to find and utilize the best available evidence. Therefo...

Introduction Diabetes is the most common cause of chronic kidney disease (CKD). Urinary albumin excretion rate (AER) and estimated glomerular filtration rate (eGFR) are commonly used to monitor the onset and progression of diabetic kidney disease (DKD). We studied if the preceding rate of kidney function decline, that is, the eGFR slope, is indepen...

To derive the maturation of neurophysiological processes from childhood to adulthood reflected by the change of motor-evoked potential (MEP) features. 38 participants were recruited from four groups (age mean in years [SD in months], number (males)): children (7.3 [4.2], 7(4)), preadolescents (10.3 [6.9], 10(5)), adolescents (15.3 [9.8], 11(5)), an...

BACKGROUND Digital behavior change interventions (DBCI) may provide scalable and cost-effective means to support lifestyle improvements and thus help prevent type 2 diabetes (T2D). The DBCIs require some minimum amount of engagement to evoke health benefits. However, sufficient amount and type of engagement, i.e., effective engagement, is not compl...

Type 2 diabetes (T2D) can be prevented or delayed through a healthy lifestyle. Digital behavior change interventions (DBCIs) may offer cost-effective and scalable means to support lifestyle changes. This study investigated associations between user engagement with a habit-formation-based DBCI, the BitHabit app, and changes in T2D risk factors over...

Background Prenatal urban environmental exposures have been associated with blood pressure in children. The dynamic of these associations across childhood and later ages is unknown. Objectives To assess associations of prenatal urban environmental exposures with blood pressure trajectories from childhood to early adulthood. Methods Repeated measure...

Objectives: (1) To develop reference values for health-related fitness in European children and adolescents aged 6–18 years that are the foundation for the web based, open-access and multi-language fitness platform (FitBack); (2) To provide comparisons across European countries. Methods: This study builds on a previous large fitness reference stud...

Background: In recent years, biologic drug therapies have altered the course of juvenile idiopathic arthritis (JIA) possibly also improving the patients’ physical fitness. However, studies measuring both cardiorespiratory and muscular fitness in children with JIA are sparse and have failed to show consistent results. Our aim was to assess both card...

Background COVID-19 severity varies widely. Although some demographic and cardio-metabolic factors, including age and obesity, are associated with increasing risk of severe illness, the underlying mechanism(s) are uncertain. Subjects/methods In a meta-analysis of three independent studies of 1471 participants in total, we investigated phenotypic a...

We evaluated the determinants of cognitive performance in children and adolescents. This is a longitudinal study, secondary analysis of the Physical Activity and Nutrition in Children (PANIC) study. We assessed 502 children (51.6% girls) at middle childhood (range: 6.6 to 9.0 years), at late childhood, 437 children (51.0% girls, range: 8.8 to 11.2...

Objectives (1) To develop reference values for health-related fitness European children and adolescents aged 6–18 years that are the foundation for the web-based, open-access and multi-language fitness platform (FitBack); (2) To provide comparisons across European countries. Methods This study builds on a previous large fitness reference study in...

Excess sugar consumption—common in youth—is associated with poor health. Evidence on the relationship between sugar consumption and the oral microbiome, however, remains scarce and inconclusive. We explored whether the diversity, composition, and functional capacities of saliva microbiota differ based on the consumption of select sugary foods and d...

Hair steroid analysis offers the possibility to evaluate long-term steroid metabolism. It is especially beneficial when studying the steroid milieu in newborns and children, for example it can provide new insights into steroid metabolism over months and is unaffected by diurnal fluctuations in steroid concentrations. This study describes a quantita...

Background Digital health interventions may offer a scalable way to prevent type 2 diabetes (T2D) with minimal burden on health care systems by providing early support for healthy behaviors among adults at increased risk for T2D. However, ensuring continued engagement with digital solutions is a challenge impacting the expected effectiveness. Obje...

Long and short sleep duration are associated with elevated blood pressure (BP), possibly through effects on molecular pathways that influence neuroendocrine and vascular systems. To gain new insights into the genetic basis of sleep-related BP variation, we performed genome-wide gene by short or long sleep duration interaction analyses on four BP tr...

Background Clinical trials have shown that type 2 diabetes (T2D) is preventable through lifestyle interventions targeting high-risk people. Nevertheless, large-scale implementation of risk identification followed by preventive interventions has proven to be challenging. Specifically, recruitment of participants into preventive interventions is an i...

Background An association between childhood anthropometric measurements and dental caries is conflicting. The prevalence and severity of dental caries and its association with anthropometric and behavioural factors, were investigated among Finnish teenagers. Methods The study sample comprised 202 15–17-year-old participants in the Physical Activit...

BACKGROUND Digital health interventions may offer a scalable way to prevent type 2 diabetes (T2D) with minimal burden on health care systems by providing early support for healthy behaviors among adults at increased risk for T2D. However, ensuring continued engagement with digital solutions is a challenge impacting the expected effectiveness. OBJE...

Educational attainment is widely used as a surrogate for socioeconomic status (SES). Low SES is a risk factor for hypertension and high blood pressure (BP). To identify novel BP loci, we performed multi-ancestry meta-analyses accounting for gene-educational attainment interactions using two variables, “Some College” (yes/no) and “Graduated College”...

Glycemic traits are used to diagnose and monitor type 2 diabetes and cardiometabolic health. To date, most genetic studies of glycemic traits have focused on individuals of European ancestry. Here we aggregated genome-wide association studies comprising up to 281,416 individuals without diabetes (30% non-European ancestry) for whom fasting glucose,...

A Correction to this paper has been published: https://doi.org/10.1038/s41588-021-00832-z.

Mielenterveyssairastavuus on Pohjois-Savossa valtakunnallisesti korkealla tasolla. Päihdesairauk-sien hoitojaksoja, alkoholikuolemia ja huumausainerikoksia oli Pohjois-Savossa vuonna 2018 enemmän kuin Suomessa keskimäärin. Nuoret ja raskaana olevat naiset tupakoivat enemmän kuin vastaavat ryhmät Suomessa. Pienituloisia kotitalouksia oli enemmän ja...

A Correction to this paper has been published: https://doi.org/10.1038/s41467-021-21276-3

Differences between sexes contribute to variation in the levels of fasting glucose and insulin. Epidemiological studies established a higher prevalence of impaired fasting glucose in men and impaired glucose tolerance in women, however, the genetic component underlying this phenomenon is not established. We assess sex-dimorphic (73,089/50,404 women...

Irisin is a novel exercise-induced myokine that may be involved in regulating energy metabolism. We determined whether overtraining syndrome (OTS) and its biochemical markers are associated with plasma irisin levels in athletes. Seven severely overtrained athletes (OA) and 10 healthy control athletes (CA) were recruited and examined at the time of...

Genetic studies of blood pressure (BP) to date have mainly analyzed common variants (minor allele frequency > 0.05). In a meta-analysis of up to ~1.3 million participants, we discovered 106 new BP-associated genomic regions and 87 rare (minor allele frequency ≤ 0.01) variant BP associations (P < 5 × 10⁻⁸), of which 32 were in new BP-associated loci...

The development of the organization of the motor representation areas in children and adolescents is not well-known. This cross-sectional study aimed to provide an understanding for the development of the functional motor areas of the upper extremity muscles by studying healthy right-handed children (6–9 years, n = 10), preadolescents (10–12 years,...

Genetic studies of blood pressure (BP) to date have mainly analyzed common variants (minor allele frequency > 0.05). In a meta-analysis of up to ~1.3 million participants, we discovered 106 new BP-associated genomic regions and 87 rare (minor allele frequency ≤ 0.01) variant BP associations (P < 5 × 10−8), of which 32 were in new BP-associated loci...

Psychological and social factors are known to influence blood pressure (BP) and risk of hypertension and associated cardiovascular diseases. To identify novel BP loci, we carried out genome-wide association meta-analyses of systolic, diastolic, pulse, and mean arterial BP taking into account the interaction effects of genetic variants with three ps...

COVID-19 severity has varied widely, with demographic and cardio-metabolic factors increasing risk of severe reactions to SARS-CoV-2 infection, but the underlying mechanisms for this remain uncertain. We investigated phenotypic and genetic factors associated with subcutaneous adipose tissue expression of Angiotensin I Converting Enzyme 2 ( ACE2 ),...

BACKGROUND Clinical trials have shown that type 2 diabetes (T2D) is preventable through lifestyle interventions targeting high-risk people. Nevertheless, large-scale implementation of risk identification followed by preventive interventions has proven to be challenging. Specifically, recruitment of participants into preventive interventions is an i...

Background Children with juvenile idiopathic arthritis (JIA) have been found to have reduced cardiorespiratory fitness and lower physical activity. Poor cardiorespiratory fitness is associated with a risk of cardiometabolic diseases. Objectives The aim of this study was to study the levels of cardiorespiratory fitness, respiratory function and hem...

Long and short sleep duration are associated with elevated blood pressure (BP), possibly through effects on molecular pathways that influence neuroendocrine and vascular systems. To gain new insights into the genetic basis of sleep-related BP variation, we performed genome-wide gene by short or long sleep duration interaction analyses on four BP tr...

Unhealthy diet has been associated with overweight, obesity, increased cardiometabolic risk, and recently, to impaired cognition and academic performance. The aim of this review is to provide an overview of the associations between health behaviors and cognition and academic achievement in children and adolescents under 18 years of age with a speci...

Background: Associations of cardiometabolic risk factors with heart rate variability (HRV) in children are unclear. We examined associations of cardiometabolic risk score (CRS) and individual cardiometabolic risk factors with HRV variables in 6-8-year-olds. Methods: The participants were a population-based sample of 443 children participating in...

Purpose To study the associations of physical activity (PA), sedentary time (ST), and cardiorespiratory fitness (CRF) with heart rate variability (HRV) in children. Methods The participants were a population sample of 377 children aged 6–9 years (49% boys). ST, light PA (LPA), moderate PA (MPA), vigorous PA (VPA), and moderate-to-vigorous PA (MVPA...

Both short and long sleep are associated with an adverse lipid profile, likely through different biological pathways. To elucidate the biology of sleep-associated adverse lipid profile, we conduct multi-ancestry genome-wide sleep-SNP interaction analyses on three lipid traits (HDL-c, LDL-c and triglycerides). In the total study sample (discovery +...

Purpose: Few studies have investigated the independent and joint associations of cardiorespiratory fitness (CRF) and body fat percentage (BF%) with insulin resistance in children. We investigated the independent and combined associations of CRF and BF% with fasting glycaemia and insulin resistance and their interactions with physical activity (PA)...

Most obese children show cardiometabolic impairments, such as insulin resistance, dyslipidemia, and hypertension. Yet some obese children retain a normal cardiometabolic profile. The mechanisms underlying this variability remain largely unknown. We examined whether genetic loci associated with increased insulin sensitivity and relatively higher fat...

Early childhood growth patterns are associated with adult health, yet the genetic factors and the developmental stages involved are not fully understood. Here, we combine genome-wide association studies with modeling of longitudinal growth traits to study the genetics of infant and child growth, followed by functional, pathway, genetic correlation,...

Background: Mendelian randomization studies in adults suggest that abdominal adiposity is causally associated with increased risk of type 2 diabetes and coronary artery disease in adults, but its causal effect on cardiometabolic risk in children remains unclear. Objective: We aimed to study the causal relation of abdominal adiposity with cardiom...

Background: Little is known about the association between adrenarche and cognition in general populations of children. We therefore studied the associations of dehydroepiandrosterone sulfate (DHEAS), androstenedione (A4), testosterone, insulin-like growth factor-1 (IGF-1), and adrenarche with cognition among prepubertal children. Methods: These...

Although hundreds of GWAS-implicated loci have been reported for adult obesity-related traits, less is known about the genetics specific for early-onset obesity, and with only a few studies conducted in non-European populations to date. Searching for additional genetic variants associated with childhood obesity, we performed a trans-ancestral meta-...

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Background The interhemispheric difference in cortical excitability and its relationship to motor functions is unclear. Aim We examined the relationship between handedness, left and right motor cortex excitability and fine and gross motor functions in adolescence. Methods 28 healthy adolescents (age 16–19 years, 19 girls) were studied. Handedness...

Background Sex is known to influence brain development. However, sex differences in cortical excitability and their relationship to motor functions is unclear. Aim We examined the sex related differences in the degree of handedness, left and right motor cortex excitability and manual dexterity. Methods 28 healthy adolescents (age 16–19 years,19 g...

Objective: Adiposity induces the clustering of cardiometabolic risk factors, and pediatric adiposity is a better indicator for adulthood cardiometabolic diseases than pediatric metabolic syndrome. However, the observed prevalence of pediatric adiposity depends on the methods and cut-points used. Therefore, we aimed to define diagnostic criteria for...

We integrate comeasured gene expression and DNA methylation (DNAme) in 265 human skeletal muscle biopsies from the FUSION study with >7 million genetic variants and eight physiological traits: height, waist, weight, waist–hip ratio, body mass index, fasting serum insulin, fasting plasma glucose, and type 2 diabetes. We find hundreds of genes and DN...