Showing papers by "Seppo Koskinen published in 2012"

Novel Loci for Adiponectin Levels and Their Influence on Type 2 Diabetes and Metabolic Traits: A Multi-Ethnic Meta-Analysis of 45,891 Individuals

Abstract: Circulating levels of adiponectin, a hormone produced predominantly by adipocytes, are highly heritable and are inversely associated with type 2 diabetes mellitus (T2D) and other metabolic traits. We conducted a meta-analysis of genome-wide association studies in 39,883 individuals of European ancestry to identify genes associated with metabolic disease. We identified 8 novel loci associated with adiponectin levels and confirmed 2 previously reported loci (P = 4.5×10(-8)-1.2×10(-43)). Using a novel method to combine data across ethnicities (N = 4,232 African Americans, N = 1,776 Asians, and N = 29,347 Europeans), we identified two additional novel loci. Expression analyses of 436 human adipocyte samples revealed that mRNA levels of 18 genes at candidate regions were associated with adiponectin concentrations after accounting for multiple testing (p<3×10(-4)). We next developed a multi-SNP genotypic risk score to test the association of adiponectin decreasing risk alleles on metabolic traits and diseases using consortia-level meta-analytic data. This risk score was associated with increased risk of T2D (p = 4.3×10(-3), n = 22,044), increased triglycerides (p = 2.6×10(-14), n = 93,440), increased waist-to-hip ratio (p = 1.8×10(-5), n = 77,167), increased glucose two hours post oral glucose tolerance testing (p = 4.4×10(-3), n = 15,234), increased fasting insulin (p = 0.015, n = 48,238), but with lower in HDL-cholesterol concentrations (p = 4.5×10(-13), n = 96,748) and decreased BMI (p = 1.4×10(-4), n = 121,335). These findings identify novel genetic determinants of adiponectin levels, which, taken together, influence risk of T2D and markers of insulin resistance.

Long-term determinants of muscle strength decline: prospective evidence from the 22-year mini-Finland follow-up survey

Abstract: Objectives: To examine long-term changes in handgrip strength and the factors predicting handgrip strength decline. Design: Longitudinal cohort study with 22 years of follow-up. Setting: Population-based Mini-Finland Health Examination Survey in Finland. Participants: Nine hundred sixty-three men and women aged 30 to 73 at baseline. Measurements: Handgrip strength was measured using a handheld dynamometer at baseline and follow-up. Information on potential risk factors, namely lifestyle and chronic conditions, and their changes throughout the follow-up were based on health interviews. Results: Based on linear mixed-effect models, midlife physically strenuous work, excess body weight, smoking, cardiovascular disease, hypertension, diabetes mellitus, and asthma predicted muscle strength decline over 22 years of follow-up (P < .05 for all). In addition, pronounced weight loss, becoming physically sedentary, persistent smoking, incident coronary heart disease, other cardiovascular disease, diabetes mellitus, chronic bronchitis, chronic back syndrome, long-lasting cardiovascular disease, hypertension, and asthma were associated with accelerated handgrip strength decline (P < .05 for all). Conclusion: Lifestyle and physical health earlier in life determine rate of muscle strength decline in old age. Efforts should be made to recognize persons at risk in a timely manner and target early interventions to middle-aged persons to slow down muscle strength decline and prevent future functional limitations and disability.

Evidence of Inbreeding Depression on Human Height

Abstract: Stature is a classical and highly heritable complex trait, with 80%–90% of variation explained by genetic factors In recent years, genome-wide association studies (GWAS) have successfully identified many common additive variants influencing human height; however, little attention has been given to the potential role of recessive genetic effects Here, we investigated genome-wide recessive effects by an analysis of inbreeding depression on adult height in over 35,000 people from 21 different population samples We found a highly significant inverse association between height and genome-wide homozygosity, equivalent to a height reduction of up to 3 cm in the offspring of first cousins compared with the offspring of unrelated individuals, an effect which remained after controlling for the effects of socio-economic status, an important confounder (χ2 = 8389, df = 1; p = 52×10−20) There was, however, a high degree of heterogeneity among populations: whereas the direction of the effect was consistent across most population samples, the effect size differed significantly among populations It is likely that this reflects true biological heterogeneity: whether or not an effect can be observed will depend on both the variance in homozygosity in the population and the chance inheritance of individual recessive genotypes These results predict that multiple, rare, recessive variants influence human height Although this exploratory work focuses on height alone, the methodology developed is generally applicable to heritable quantitative traits (QT), paving the way for an investigation into inbreeding effects, and therefore genetic architecture, on a range of QT of biomedical importance

Mortality in people with depressive, anxiety and alcohol use disorders in Finland

Abstract: Background Mental disorders are associated with increased mortality, but population-based surveys with reliable diagnostic procedures controlling for somatic health status are scarce. Aims To assess excess mortality associated with depressive, anxiety and alcohol use disorders and the principal causes of death. Method In a nationally representative sample of Finns aged 30–70 years, psychiatric disorders were diagnosed with the Composite International Diagnostic Interview. After an 8-year follow-up period, vital status and cause of death of each participant was obtained from national registers. Results After adjusting for sociodemographic factors, health status and smoking, depressive (hazard ratio (HR) = 1.97) and alcohol use disorders (HR = 1.72) were statistically significantly associated with mortality. Risk of unnatural death was increased among individuals diagnosed with anxiety disorders or alcohol dependence. Conclusions Individuals with depressive and alcohol use disorders have an increased mortality risk comparable with many chronic somatic conditions, that is only partly attributable to differences in sociodemographic, somatic health status and hazardous health behaviour.

Living alone and antidepressant medication use: a prospective study in a working-age population

Abstract: An increasing proportion of the population lives in one-person households. The authors examined whether living alone predicts the use of antidepressant medication and whether socioeconomic, psychosocial, or behavioral factors explain this association. The participants were a nationally representative sample of working-age Finns from the Health 2000 Study, totaling 1695 men and 1776 women with a mean age of 44.6 years. In the baseline survey in 2000, living arrangements (living alone vs. not) and potential explanatory factors, including psychosocial factors (social support, work climate, hostility), sociodemographic factors (occupational grade, education, income, unemployment, urbanicity, rental living, housing conditions), and health behaviors (smoking, alcohol use, physical activity, obesity), were measured. Antidepressant medication use was followed up from 2000 to 2008 through linkage to national prescription registers. Participants living alone had a 1.81-fold (CI = 1.46-2.23) higher purchase rate of antidepressants during the follow-up period than those who did not live alone. Adjustment for sociodemographic factors attenuated this association by 21% (adjusted OR = 1.64, CI = 1.32-2.05). The corresponding attenuation was 12% after adjustment for psychosocial factors (adjusted OR = 1.71, CI = 1.38-2.11) and 9% after adjustment for health behaviors (adjusted OR = 1.74, CI = 1.41-2.14). Gender-stratified analyses showed that in women the greatest attenuation was related to sociodemographic factors and in men to psychosocial factors. These data suggest that people living alone may be at increased risk of developing mental health problems. The public health value is in recognizing that people who live alone are more likely to have material and psychosocial problems that may contribute to excess mental health problems in this population group.

Marital history 1971–91 and mortality 1991–2004 in England & Wales and Finland

Abstract: Background Little is known about the effects of long-term marital history on mortality, and the relative importance of using marital history instead of baseline marital status in mortality analyses. No previous comparative studies on the associations of marital history and mortality exist. Methods Longitudinal data from England & Wales and from Finland were used to assess the effects of marital history, constructed from census records from years 1971, 1981 and 1991, on all-cause mortality in 1991–2004 among men and women aged ≥50 years. Data from England & Wales include 57 492 deaths; data from Finland include 424 602 deaths. Poisson regression analysis was applied. Results Adding marital history into models including baseline marital status was statistically significant when explaining male mortality, while it was generally not important for female mortality. Adjusted for socio-demographic covariates, those consistently married with no record of marital break-up had the lowest mortality rates among both men and women aged 50–74 in both countries. Those never married, those divorced with a history of divorce and those widowed with a history of widowhood showed the highest mortality risks. Associations between marital history and mortality were weaker among those aged 75+. Conclusions Consistent evidence in favour of both protective effects of long-lasting marriage and detrimental effects of marital dissolution were found. Studies would benefit from including marital history in the models instead of baseline marital status whenever possible, especially when studying male mortality.

Osteochondritis dissecans of the humeral capitellum in identical twins

Abstract: Osteochondritis dissecans (OCD) of the humeral capitellum is a disorder affecting mainly boys between the ages of 12 and 15 years. The exact etiology of OCD is not clear, but it is believed that repetitive trauma is the primary cause. Genetic factors are thought to play a secondary role in the pathogenesis. We present 17-year-old identical twins with similar MRI and arthroscopic findings, suggesting that genetic components are involved in the etiology of OCD of the humeral capitellum.

Scaphoid Fractures: Assessment of Fracture Healing after Screw Fixation Using a Novel Mobile Dedicated Extremity Cone-beam CT (CBCT) Scanner

Abstract: Poster: "ECR 2012 / C-0454 / Scaphoid Fractures: Assessment of Fracture Healing after Screw Fixation Using a Novel Mobile Dedicated Extremity Cone-beam CT (CBCT) Scanner" by: "V. Haapamaki1, S. K. Koskinen2; 1HUS Helsinki/FI, 2Helsinki/FI"