Institute for Molecular Medicine FIMM

Helsinki, Finland

Institute for Molecular Medicine FIMM

Helsinki, Finland
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Korja M.,University of Helsinki | Lehto H.,University of Helsinki | Kaprio J.,University of Helsinki | Kaprio J.,Finnish National Institute for Health and Welfare | Kaprio J.,Institute for Molecular Medicine FIMM
Neurology | Year: 2016

Objective: To determine the nationwide incidence of subarachnoid hemorrhage (SAH) and report nationwide changes in smoking rates between 1998 and 2012 in Finland. Methods: In this register-based study, we utilized the nationwide Causes of Death Register and Hospital Discharge Register in identifying SAH events between 1998 and 2012. Population statistics in Finland, which were obtained through a database of Statistics Finland, were used to calculate crude annual incidence rates of SAH. For the direct age standardization of crude incidence rates, we used the European Standard Population (ESP) 2013. Data on changes in nationwide smoking rates between 1998 and 2012 were extracted from a database of the National Institute for Health and Welfare. Results: For the total of 79,083,579 cumulative person-years, we identified 6,885 people with SAH. Sudden deaths from SAH away from hospitals or in emergency rooms accounted for 1,771 (26%) of the events. Crude nationwide annual incidence rates varied between 6.2 and 10.0 per 100,000 persons, and increased by age particularly in women. Among 70- to 75-year-old women, the incidence of SAH was highest (22.5 per 100,000 persons). The 3-year average of ESP standardized incidence decreased 24% from 11.7 in 1998-2000 to 8.9 per 100,000 persons in 2010-2012. Daily smoking decreased 30% between 1998 and 2012. Conclusions: The incidence of SAH seems to be decreasing. This tendency may be coupled with changes in smoking rates. The incidence of SAH in Finland is similar to other Nordic countries. © 2016 American Academy of Neurology.

Silventoinen K.,University of Helsinki | Helle S.,University of Turku | Nisen J.,University of Helsinki | Martikainen P.,University of Helsinki | And 3 more authors.
Twin Research and Human Genetics | Year: 2013

The associations between height and reproductive success in humans have attracted long-time scientific interest, but in addition to rather mixed previous results, little is still known about the background mechanisms of these associations. We analyzed the association of adult height with age at first birth and lifetime reproductive success using a twin study design that is able to optimally take into account family background and estimate the contributions of genetic and environmental factors. Information on live births as of June 2009 for 7,830 Finnish twins born 1950-1957 was extracted from the national population register. We found evidence for non-linear associations in men, as men in the third sex-specific height quintile had the highest probability of having one to two children, or three or more children at individual level analyses, and also to have any children when analyzing twin pairs discordant for height. Furthermore, the probability of having a spouse was highest in the third height category in men. Short stature was associated with earlier age at first birth in females, explained by correlated genetic factors, but not with lifetime number of children or having a spouse. Our results suggest that average stature may give some advantage for reproduction in males. In females, genetic factors explained the association between short stature and young age at first birth, which may suggest the role of hormonal factors. © The Authors 2013.

Korja M.,University of Helsinki | Korja M.,Macquarie University | Silventoinen K.,University of Helsinki | Laatikainen T.,Finnish National Institute for Health and Welfare | And 8 more authors.
PLoS ONE | Year: 2013

Background:Prospective studies on the risk factors for subarachnoid hemorrhage (SAH) are limited. Moreover, the effect of risk factors on the incidence rates of SAH is not well known about.Aims:In this study, we aimed to identify risk factors for SAH and characterize subgroups in a population with a high incidence of SAH.Methods:After recording multiple potential risk factors for SAH at the time of enrolment, first ever SAH events between 1972 and 2009 were recorded through the nationwide Causes of Death Register and Hospital Discharge Register for the population-based cohort of 64 349 participants, who participated in the National FINRISK Study between 1972 and 2007 in Finland.Results:During the follow-up time of 1.26 million person-years (median 17.9 years, range 0 to 37.9 years), 437 persons experienced fatal or non-fatal SAH. Crude SAH incidence was 34.8 (95% confidence interval: 31.7-38.2) per 100 000 person-years among ≥25-year-old persons. Female sex, high blood pressure values and current smoking were confirmed as risk factors for SAH. Previous myocardial infarction, history of premature stroke (any kind) in mother and elevated cholesterol levels in men were identified as new risk factors for SAH. Depending on the combination of risk factors, SAH incidence varied between 8 and 171 per 100 000 person-years.Conclusions:New and previously reported risk factors appear to have a much stronger association with the incidence of SAH than is ordinarily seen in cardiovascular diseases. Risk factor assessments may facilitate the identification of high-risk persons who should be the focus of preventive interventions. © 2013 Korja et al.

Sihvola E.,University of Helsinki | Rose R.J.,Indiana University Bloomington | Dick D.M.,Virginia Commonwealth University | Korhonen T.,University of Helsinki | And 7 more authors.
Psychological Medicine | Year: 2011

Background Clinically ascertained reports suggest that boys and girls with attention deficit hyperactivity disorder (ADHD) may differ from each other in their vulnerability to substance use problems.Method A total of 1545 Finnish adolescents were assessed for DSM-IV-based ADHD symptoms by their parents and classroom teachers using standardized rating scales at age 11-12 years. At age 14, substance use disorders and psychiatric co-morbidity were assessed with the Semi-Structured Assessment for the Genetics of Alcoholism, providing DSM-III-R/DSM-IV diagnoses for Axis I disorders. At age 17.5, substance use was assessed by multi-item questionnaire.Results Although baseline ADHD symptoms were less common among females, they were more predictive of adverse substance use outcomes once conduct disorder and previous substance use were controlled for. Only in females were baseline ADHD symptoms significant predictors of alcohol abuse and dependence and illicit drug use at age 14. At the age of 17.5, parents' reports of inattentiveness and hyperactivity were significant predictors for frequent alcohol use in both sexes, but they were more predictive of frequent alcohol and illicit drug use in girls. Impulsivity in teachers' ratings predicted frequent alcohol use and illicit drug use in boys. Parental reports of inattentiveness in their 11-/12-year-old daughters were a consistent predictor for illicit drug use across adolescence.Conclusions Inattentiveness and hyperactivity may be more predictive of alcohol use disorders and maladaptive patterns of alcohol and illicit drug use among girls than boys. The importance of these behavioural symptoms should be assessed further in the community, as they could jeopardize adolescents' successful transitioning into adult roles. © 2011 Cambridge University Press.

Leskinen T.,University of Jyväskylä | Sipila S.,University of Jyväskylä | Kaprio J.,University of Helsinki | Kaprio J.,Institute for Molecular Medicine FIMM | And 5 more authors.
Age | Year: 2013

Exercise-induced positive changes in skeletal muscle properties and metabolism decrease the risk for disability, cardiometabolic diseases and mortality. Here, we studied muscle properties and glucose homeostasis in a non-exercise stage in twin pairs with cotwins discordant for physical activity habits for at least 32 years of their adult lives. Isometric knee extension force, MR imaging of midthigh tissue composition and muscle volume, and fasting blood samples were acquired from 16 same-sex (seven monozygotic, nine dizygotic) middle-aged and older twin pairs. The consistently active twins had 20 % higher knee extension forces than their inactive co-twins (p=0.006) although the active twins had only 4 % higher midthigh muscle cross-sectional areas (p=0.072). These results were similar in intrapair analysis in which only the seven identical twin pairs were included. The ratio between the area of midthigh fat and muscle tissues was significantly lower among the active twins (0.65 vs. 0.48, p=0.006). The active twins had also lower fasting plasma glucose levels (5.1 vs 5.6 mmol/l, p=0.041). The area of midthigh intramuscular (extramyocellular) fat was associated with the markers of glucose homeostasis, especially with glycated hemoglobin, and these associations were emphasized by the diabetic and inactive twins. Regular exercise throughout the adult life retains muscle strength and quality but not necessarily mass. The regular use of muscles also prevents from the accumulation of intramuscular fat which might be related to maintained glucose metabolism and, thus, prevention of metabolic disorders. © 2012 American Aging Association.

Silventoinen K.,University of Helsinki | Kaprio J.,University of Helsinki | Kaprio J.,Finnish National Institute for Health and Welfare | Kaprio J.,Institute for Molecular Medicine FIMM | Yokoyama Y.,Osaka City University
Behavior Genetics | Year: 2011

We analyzed the genetic architecture of prepubertal development of relative weight to height in 216 monozygotic and 159 dizygotic complete Japanese twin pairs (52% girls). Ponderal index at birth (kg/m 3) and body mass index (BMI, kg/m 2) from 1 to 11 years of age were used. Additive genetic factors explained the major proportion (52-74%) of the variation of BMI from 1 to 11 years of age. Environmental factors common to both co-twins also showed some effect (7-28%), but at most ages this was not statistically significant. Strong genetic tracking was found for BMI from 1 to 11 years of age, but there was also evidence for a persistent effect of common environmental factors. Our results suggest that the genetic architecture of BMI development in the Japanese population is generally similar to that found in previous twin studies in Caucasian populations. © 2010 Springer Science+Business Media, LLC.

Korja M.,University of Helsinki | Silventoinen K.,University of Helsinki | Laatikainen T.,Finnish National Institute for Health and Welfare | Laatikainen T.,University of Eastern Finland | And 6 more authors.
Neurology | Year: 2013

Objective: To assess long-term, cause-specific mortality rates and rate ratios of the patients alive at 1 year after subarachnoid hemorrhage (SAH). Methods: The population-based, prospective, cohort study with a nested case-control design consisted of 64,349 persons (aged 25-74 years at enrollment) who participated in the National FINRISK Study between 1972 and 2007. Four hundred thirty-seven SAH cases, 233 one-year SAH survivors, and their matched intrinsic controls were identified and followed up until the end of 2009 through the nationwide Finnish Causes of Death Register. All-cause mortality rates and rate ratios of the 1-year SAH survivors and controls were the main outcome measures. Results: Eighty-eight (37.8%) of 233 one-year SAH survivors died during the total follow-up time of 2,487 person-years (median 8.6 years, range 0.1-35.8 years). The 1-year SAHsurvivors had a hazard ratio of 1.96 (95% confidence interval 1.57-2.47) for death compared with the matched general population with 10 controls for each SAH survivor. One-year SAH survivors had up to 31 additional deaths per 1,000 person-years compared with controls with minimal cerebrovascular risk factors. The higher long-termrisk of death among SAH survivorswas attributed solely to cerebrovascular diseases, andmost importantmodifiable risk factors for death were smoking, high systolic blood pressure (≥159 mm Hg), and high cholesterol levels (≥7.07 mmol/L). Conclusion: One-year SAH survivors have excess mortality, which is attributed to an exceptional risk of deadly cerebrovascular events. Aggressive post-SAH cerebrovascular risk factor intervention strategies are highly warranted. © 2013 American Academy of Neurology.

Pietilainen K.H.,University of Helsinki | Korkeila M.,University of Helsinki | Bogl L.H.,University of Helsinki | Westerterp K.R.,Maastricht University | And 5 more authors.
International Journal of Obesity | Year: 2010

Objective:To study whether eating or physical-activity (PA) habits differ between obese and non-obese monozygotic (MZ) co-twins independent of genetic effects.Methods:Rare MZ pairs discordant for obesity (n=14, body mass index difference 5.21.8 kg m-2) and weight-concordant control pairs (n=10, 1.00.7 kg m-2), identified through a population-based registry of 24-28-year-old twins (n658 MZ pairs), completed 3-day food and PA diaries and eating behavior questionnaires. Each twin was asked to compare his/her own eating and PA patterns with the co-twin's behavior by structured questionnaires. Accuracy of energy intake was validated by doubly labeled water.Results:Non- obese co-twins consistently reported that their obese twin siblings ate more food overall, consumed less healthy foods and exercised less than the non-obese co-twins do. However, no differences in energy intake (9.6±1.0 MJ per day vs 9.8±1.1 MJ per day, respectively) in the food diaries or in the mean PA level (1.74±0.02 vs 1.79±0.04, respectively) in the PA diaries were found between obese and non-obese co-twins. A considerable underreporting of energy intake (3.2±1.1 MJ per day, P=0.036) and overreporting of PA (1.8±0.8 MJ per day, P=0.049) was observed in the obese, but not in the non-obese co-twins.Conclusions:On the basis of rare MZ twin pairs discordant for obesity, the co-twin assessments confirmed substantial differences in eating and PA behavior between obese and non-obese persons. These may be overlooked in population studies using food and PA diaries because of considerable misreporting by the obese. © 2010 Macmillan Publishers Limited All rights reserved.

Silventoinen K.,University of Helsinki | Kaprio J.,University of Helsinki | Kaprio J.,Finnish National Institute for Health and Welfare | Kaprio J.,Institute for Molecular Medicine FIMM | Yokoyama Y.,Osaka City University
Annals of Human Biology | Year: 2011

Background: Genetic factors explain a major part of the variation of adult stature, but little is still known on the genetics of growth, especially in non-Caucasian populations. Aim: To analyse the quantitative genetics of pre-pubertal growth in Japanese children. Subjects and methods: Data from birth until 11 years of age were collected on 349 complete twin pairs based on previously recorded height measures. The data were analysed using two different multivariate models by the Mx statistical package. Results: No major sex differences were found and thus boys and girls were analysed together. Since 1 year of age, genetic factors explained from 42-71% and environmental factors shared by co-twins from 14-33% of the variation of height. Genetic continuity of height was high and 75% of the genetic variance was shared since 1 year of age. Environmental factors affecting height showed weaker correlations between early and late childhood than genetic factors. Conclusion: Growth from early to late childhood is largely regulated by the same set of genes. However, also environmental factors shared by co-twins are important for growth. Identifying specific environmental factors affecting growth has potentially important public health implications, even in an affluent society such as Japan. © Informa UK, Ltd.

Silventoinen K.,University of Helsinki | Rokholm B.,Copenhagen University | Kaprio J.,University of Helsinki | Kaprio J.,National Health Research Institute | And 2 more authors.
International Journal of Obesity | Year: 2010

In this systematic review, we aimed to collect together all previous twin and adoption studies on childhood and adolescent obesity up to the age of 18 years. Using several sources, we identified nine twin and five adoption studies; all of these studies had used relative weight as an indicator of obesity. Except the two twin studies from the Korean population, all studies represented Caucasian populations. In a meta-analysis of these twin studies, we found that genetic factors had a strong effect on the variation of body mass index (BMI) at all ages. The common environmental factors showed a substantial effect in mid-childhood, but this effect disappeared at adolescence. Adoption studies supported the role of family environment in childhood obesity as correlations were found between adoptees and adoptive parents; however, correlations were substantially stronger between parents and their biological offspring, further supporting the importance of genetic factors. In the future, more studies implementing genetic and environmental measures into twin models are needed as they allow estimation of the proportion of total genetic variation explained by candidate genes and analyses of gene-environment interactions. More studies of genetic architecture in non-Caucasian populations, of gene-environment interactions, and of body composition and body fat distribution are needed. © 2010 Macmillan Publishers Limited. All rights reserved.

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