Browsing by Subject "POOLED ANALYSIS"

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  • Premenopausal Breast Canc Collabor (2018)
    IMPORTANCE The association between increasing body mass index (BMI; calculated as wei ght in kilograms divided by height in meters squared) and risk of breast cancer is unique in cancer epidemiology in that a crossover effect exists, with risk reduction before and risk increase after menopause. The inverse association with premenopausal breast cancer risk is poorly characterized but might be important in the understanding of breast cancer causation. OBJECTIVE To investigate the association of BMI with premenopausal breast cancer risk, in particular by age at BMI, attained age, risk factors for breast cancer, and tumor characteristics. DESIGN, SETTING, AND PARTICIPANTS This multicenter analysis used pooled individual-level data from 758 592 premenopausal women from 19 prospective cohorts to estimate hazard ratios (HRs) of premenopausal breast cancer in association with BMI from ages 18 through 54 years using Cox proportional hazards regression analysis. Median follow-up was 9.3 years (interquartile range, 4.9-13.5 years) per participant, with 13 082 incident cases of breast cancer. Participants were recruited from January 1,1963, through December 31, 2013, and data were analyzed from September 1.2013, through December 31, 2017. EXPOSURES Body mass index at ages 18 to 24, 25 to 34,35 to 44, and 45 to 54 years. MAIN OUTCOMES AND MEASURES Invasive or in situ premenopausal breast cancer. RESULTS Among the 758 592 premenopausal women (median age, 40.6 years; interquartile range, 35.2-45.5 years) included in the analysis, inverse linear associations of BMI with breast cancer risk were found that were stronger for BMI at ages 18 to 24 years (HR per 5 kg/m(2) [5.0-U] difference, 0.77; 95% CI, 0.73-0.80) than for BMI at ages 45 to 54 years (HR per 5.0-U difference, 0.88; 95% CI, 0.86-0.91). The inverse associations were observed even among nonoverweight women. There was a 4.2-fold risk gradient between the highest and lowest BMI categories (BMI >= 35.0 vs CONCLUSIONS AND RELEVANCE The results of this study suggest that increased adiposity is associated with a reduced risk of premenopausal breast cancer at a greater magnitude than previously shown and across the entire distribution of BMI. The strongest associations of risk were observed for BMI in early adulthood. Understanding the biological mechanisms underlying these associations could have important preventive potential.
  • Ahola-Olli, Ari V.; Mustelin, Linda; Kalimeri, Maria; Kettunen, Johannes; Jokelainen, Jari; Auvinen, Juha; Puukka, Katri; Havulinna, Aki S.; Lehtimäki, Terho; Kähönen, Mika; Juonala, Markus; Keinänen-Kiukaanniemi, Sirkka; Salomaa, Veikko; Perola, Markus; Järvelin, Marjo-Riitta; Ala-Korpela, Mika; Raitakari, Olli; Wurtz, Peter (2019)
    Aims/hypothesis Metabolomics technologies have identified numerous blood biomarkers for type 2 diabetes risk in case-control studies of middle-aged and older individuals. We aimed to validate existing and identify novel metabolic biomarkers predictive of future diabetes in large cohorts of young adults. Methods NMR metabolomics was used to quantify 229 circulating metabolic measures in 11,896 individuals from four Finnish observational cohorts (baseline age 24-45 years). Associations between baseline metabolites and risk of developing diabetes during 8-15 years of follow-up (392 incident cases) were adjusted for sex, age, BMI and fasting glucose. Prospective metabolite associations were also tested with fasting glucose, 2 h glucose and HOMA-IR at follow-up. Results Out of 229 metabolic measures, 113 were associated with incident type 2 diabetes in meta-analysis of the four cohorts (ORs per 1 SD: 0.59-1.50; p Conclusions/interpretation Metabolic biomarkers across multiple molecular pathways are already predictive of the long-term risk of diabetes in young adults. Comprehensive metabolic profiling may help to target preventive interventions for young asymptomatic individuals at increased risk.
  • TRISP Collaboration (2018)
    Purpose The ThRombolysis in Ischemic Stroke Patients (TRISP) collaboration aims to address clinically relevant questions about safety and outcomes of intravenous thrombolysis (IVT) and endovascular thrombectomy. The findings can provide observational information on treatment of patients derived from everyday clinical practice. Participants TRISP is an open, investigator-driven collaborative research initiative of European stroke centres with expertise in treatment with revascularisation therapies and maintenance of hospital-based registries. All participating centres made a commitment to prospectively collect data on consecutive patients with stroke treated with IVT using standardised definitions of variables and outcomes, to assure accuracy and completeness of the data and to adapt their local databases to answer novel research questions. Findings to date Currently, TRISP comprises 18 centres and registers >10000IVT-treated patients. Prior TRISP projects provided evidence on the safety and functional outcome in relevant subgroups of patients who were excluded, under-represented or not specifically addressed in randomised controlled trials (ie, pre-existing disability, cervical artery dissections, stroke mimics, prior statin use), demonstrated deficits in organisation of acute stroke care (ie, IVT during non-working hours, effects of onset-to-door time on onset-to-needle time), evaluated the association between laboratory findings on outcome after IVT and served to develop risk estimation tools for prediction of haemorrhagic complications and functional outcome after IVT. Future plans Further TRISP projects to increase knowledge of the effect and safety of revascularisation therapies in acute stroke are ongoing. TRISP welcomes participation and project proposals of further centres fulfilling the outlined requirements. In the future, TRISP will be extended to include patients undergoing endovascular thrombectomy.
  • de Oliveira Figueiredo, Rejane Augusta; Weiderpass, Elisabete; Tajara, Eloiza Helena; Strom, Peter; Carvalho, Andre Lopes; de Carvalho, Marcos Brasilino; Kanda, Jossi Ledo; Moyses, Raquel Ajub; Wunsch-Filho, Victor (2016)
    Introduction: Diabetes mellitus (DM (Diabetes Mellitus)) is directly associated with some cancers. However, studies on the association between diabetes mellitus and head and neck cancer (HNC (Head and Neck Cancer)) have rendered controversial results. The objective of this study was to evaluate the association between DM and HNC, as well as the impact of metformin use on the risk of HNC. Material and methods: This case-control study was conducted within the framework of the Brazilian Head and Neck Genome Project in 2011-2014. The study included 1021 HNC cases with histologically confirmed squamous cell carcinoma of the head and neck admitted to five large hospitals in Sao Paulo state. A total of 1063 controls were selected in the same hospitals. Odds ratios (OR) and 95% confidence intervals (CI) were estimated using unconditional logistic regression. Results: Diabetic participants had a decreased risk of HNC (OR = 0.68; 95% CI: 0.49-0.95) than nondiabetic participants, and this risk was further decreased among diabetic metformin users (OR = 0.54; 95% CI: 0.29-0.99). Diabetic metformin users that were current smokers (OR = 0.13; 95% CI: 0.04-0.44) or had an alcohol consumption of >40 g/day (OR = 0.31; 95% CI: 0.11-0.88) had lower risk of HNC than equivalent non-diabetic participants. Conclusion: The risk of HNC was decreased among diabetic participants; metformin use may at least partially explain this inverse association. (C) 2016 Elsevier Ltd. All rights reserved.
  • Taskinen, Marja-Riitta; Del Prato, Stefano; Bujas-Bobanovic, Maja; Louie, Michael J.; Letierce, Alexia; Thompson, Desmond; Colhoun, Helen M. (2018)
    Background and aims: Alirocumab, a monoclonal antibody to proprotein convertase subtilisin/kexin type 9, significantly reduces low-density lipoprotein cholesterol (LDL-C). We evaluated the efficacy and safety of alirocumab in individuals with type 2 diabetes mellitus (T2DM) with versus without mixed dyslipidaemia (MDL, defined as baseline LDL-C >= 70 mg/dL [1.8 mmol/L] and triglycerides >= 150mg/dL [1.7 mmol/L]). Methods: Data from 812 individuals with T2DM, from the placebo-controlled, 78-week, Phase 3 ODYSSEY LONG TERM trial of alirocumab 150mg every 2 weeks (Q2W), on a background of maximally tolerated statins +/- other lipid-lowering therapies, were pooled according to MDL status. Efficacy endpoints included percentage change from baseline to Week 24 in calculated LDL-C and other lipids/lipoproteins. Results: In individuals with T2DM who received alirocumab 150mg Q2W, mean LDL-C changes from baseline to Week 24 were -62.6% (vs. -6.0% with placebo) in those with MDL and -56.1% (vs. 5.6%) in those without MDL, with no significant between-group difference (p-interaction = 0.0842). Risk-based LDL-C goals ( Conclusions: Reductions in LDL-C and other lipids with alirocumab, as well as safety and tolerability, were comparable between individuals with T2DM and with versus without MDL. (c) 2018 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (
  • Mroueh, Rayan; Tanskanen, Tomas; Haapaniemi, Aaro; Salo, Tuula; Malila, Nea; Mäkitie, Antti; Pitkäniemi, Janne (2020)
    Background Reported patterns of familial aggregation of head and neck cancer (HNC) vary greatly, with many studies hampered by the limited number of subjects. Methods Altogether 923 early-onset ( Results Of all early-onset HNC families, only 21 (2.3%) had familial HNC cancers at any age and less than five familial early onset HNC cancers among first-degree relatives. The cumulative risk of HNC for siblings by age 60 (0.52%) was at population level (0.33%). No increased familial risk of early-onset HNC could be discerned in family members (SIR 2.68, 95% CI 0.32-9.68 for first-degree relatives). Conclusions Our study indicates that the cumulative and relative familial risk of early-onset HNC is modest in the Finnish population and, at most, only a minor proportion of early-onset HNCs are due solely to inherited genetic mutations.
  • Konttinen, H.; Llewellyn, C.; Silventoinen, K.; Joensuu, A.; Männistö, S.; Salomaa, V.; Jousilahti, P.; Kaprio, J.; Perola, M.; Haukkala, A. (2018)
    OBJECTIVES: There is no consensus on whether cognitive control over food intake (that is, restrained eating) is helpful, merely ineffective or actually harmful in weight management. We examined the interplay between genetic risk of obesity, restrained eating and changes in body weight and size. METHODS: Participants were Finnish aged 25-74 years who attended the Dietary. Lifestyle and Genetic determinants of Obesity and Metabolic syndrome study at baseline in 2007 and follow-up in 2014. At baseline (n=5024), height, weight and waist circumference (WC) were measured in a health examination and participants self-reported their weight at age 20 years. At follow-up (n=3735), height, weight and WC were based on measured or self-reported information. We calculated 7-year change in body mass index (BMI) and WC and annual weight change from age 20 years to baseline. Three-Factor Eating Questionnaire-R18 was used to assess restrained eating. Genetic risk of obesity was assessed by calculating a polygenic risk score of 97 known BMI-related loci. RESULTS: Cross-lagged autoregressive models indicated that baseline restrained eating was unrelated to 7-year change in BMI (beta=0.00; 95% confidence interval (CI) =-0.01, 0.02). Instead, higher baseline BMI predicted greater 7-year increases in restrained eating (beta = 0.08; 95% CI =0.05, 0.11). Similar results were obtained with WC. Polygenic risk score correlated positively with restrained eating and obesity indicators in both study phases, but it did not predict 7-year change in BMI or WC. However, individuals with higher genetic risk of obesity tended to gain more weight from age 20 years to baseline, and this association was more pronounced in unrestrained eaters than in restrained eaters (P=0.038 for interaction). CONCLUSIONS: Our results suggest that restrained eating is a marker for previous weight gain rather than a factor that leads to future weight gain in middle-aged adults. Genetic influences on weight gain from early to middle adulthood may vary according to restrained eating, but this finding needs to be replicated in future studies.
  • NCD Risk Factor Collaboration NCD-; Iurilli, Maria L. C.; Zhou, Bin; Eriksson, Johan G. (2021)
    From 1985 to 2016, the prevalence of underweight decreased, and that of obesity and severe obesity increased, in most regions, with significant variation in the magnitude of these changes across regions. We investigated how much change in mean body mass index (BMI) explains changes in the prevalence of underweight, obesity, and severe obesity in different regions using data from 2896 population-based studies with 187 million participants. Changes in the prevalence of underweight and total obesity, and to a lesser extent severe obesity, are largely driven by shifts in the distribution of BMI, with smaller contributions from changes in the shape of the distribution. In East and Southeast Asia and sub-Saharan Africa, the underweight tail of the BMI distribution was left behind as the distribution shifted. There is a need for policies that address all forms of malnutrition by making healthy foods accessible and affordable, while restricting unhealthy foods through fiscal and regulatory restrictions.
  • Högnäs, Emma; Kauppila, Antti; Hinkula, Marianne; Tapanainen, Juha S.; Pukkala, Eero (2016)
    Background. Many studies have previously revealed evidence of an association between grand multiparity (five or more deliveries) and gynaecological cancer. Oestrogen has an impact on cancer formation and the amount of circulating oestrogen is significantly higher during pregnancy. Also the lifestyle of grand multiparous women differs somewhat from the average population. Considering these factors it is plausible that also non-gynaecological cancers are associated with multiparity. The aim of our study was to determine cancer incidence among grand multiparous women, with special attention to non-gynaecological cancers. Material and methods. All 102 541 women alive in 1974-2011 and having had at least five deliveries were identified in the Finnish Population Register and followed up for cancer incidence through the Finnish Cancer Registry to the end of 2011. Standardised incidence ratios (SIRs) were defined as ratios between observed and expected numbers of cases, the latter ones based on incidence in the entire Finnish female population. Results. The overall incidence of non-gynaecological cancers was the same as in the reference population (SIR 0.98, 95% confidence interval 0.90-1.06). The incidence of cancers of the gall-bladder (SIR 1.42, 1.26-1.58), biliary tract (1.19, 1.04-1.35) and kidney (1.22, 1.14-1.31) was increased. There were significantly fewer cases than expected of urinary bladder cancer (SIR 0.70, 0.61-0.78), lung cancer (0.87, 0.81-0.92), colon cancer (0.94, 0.89-0.99) and all types of skin cancers. As a consequence of the decreased incidence of gynaecological cancers (SIR 0.74, 0.71-0.77) and breast cancer (0.60, 0.58-0.61), the SIR for cancer overall was 0.84 (0.83-0.85). Conclusion. The study demonstrated that grand multiparous women have a similar overall risk of non-gynaecological cancers as other women, despite significant differences in some specific forms of cancer.
  • Seppälä, Laura K.; Vettenranta, Kim; Pitkäniemi, Janne; Hirvonen, Elli; Leinonen, Maarit K.; Madanat-Harjuoja, Laura-Maria (2020)
    An association between maternal diabetes, its medication and childhood cancer has not been previously explored in a registry-based setting. With a case-control design, we aimed to explore whether maternal diabetes is associated with an increased risk of childhood cancer in the offspring. Combining data from population-based registries, we analyzed a total of 2,029 cases, i.e. persons with childhood cancer diagnosed under the age of 20?years between years 1996-2014 and a total of 10,103 matched population controls. The mothers of the cases/controls and their diagnoses of diabetes (DM) before/during pregnancy as well as their insulin/metformin prescriptions during pregnancy were identified. Conditional logistic regression modelling was used to analyze the risk of childhood cancer. The OR for childhood cancer among those exposed to any maternal diabetes was 1.32 (95% CI 1.14-1.54) compared to the offspring of the non-diabetic mothers. The effect of maternal diabetes on the risk of childhood cancer remained elevated even after adjusting for maternal age, parity and smoking. Our data suggest that maternal diabetes medication may reduce the risk for childhood cancer (adjusted OR 0.83, 95% CI 0.36-1.94), especially in gestational diabetes (adjusted OR 0.26, 95% CI 0.05-1.25), compared to the diabetic mothers without medication. The risk of childhood leukemia was significantly higher among children exposed to any maternal diabetes (OR 1.36, CI 1.04-1.77) compared to the unexposed. Maternal diabetes appears to be associated with an increased risk of childhood cancer in the offspring. The possible risk-reducing effect of an exposure to diabetes medication on offspring cancer risk warrants further investigation. This article is protected by copyright. All rights reserved.
  • Early Growth Genetics Consortium; Vogelezang, Suzanne; Bradfield, Jonathan P.; Ahluwalia, Tarunveer S.; Eriksson, Johan G.; Leinonen, Jaakko T.; Widen, Elisabeth (2020)
    The genetic background of childhood body mass index (BMI), and the extent to which the well-known associations of childhood BMI with adult diseases are explained by shared genetic factors, are largely unknown. We performed a genome-wide association study meta-analysis of BMI in 61,111 children aged between 2 and 10 years. Twenty-five independent loci reached genome-wide significance in the combined discovery and replication analyses. Two of these, located nearNEDD4LandSLC45A3, have not previously been reported in relation to either childhood or adult BMI. Positive genetic correlations of childhood BMI with birth weight and adult BMI, waist-to-hip ratio, diastolic blood pressure and type 2 diabetes were detected (R(g)ranging from 0.11 to 0.76, P-values Author summary Although twin studies have shown that body mass index (BMI) is highly heritable, many common genetic variants involved in the development of BMI have not yet been identified, especially in children. We studied associations of more than 40 million genetic variants with childhood BMI in 61,111 children aged between 2 and 10 years. We identified 25 genetic variants that were associated with childhood BMI. Two of these have not been implicated for BMI previously, located close to the genesNEDD4LandSLC45A3. We also show that the genetic background of childhood BMI overlaps with that of birth weight, adult BMI, waist-to-hip-ratio, diastolic blood pressure, type 2 diabetes, and age at menarche. Our results suggest that the biological processes underlying childhood BMI largely overlap with those underlying adult BMI. However, the overlap is not complete. Additionally, the genetic backgrounds of childhood BMI and other cardio-metabolic phenotypes are overlapping. This may mean that the associations of childhood BMI and later cardio-metabolic outcomes are partially explained by shared genetics, but it could also be explained by the strong association of childhood BMI with adult BMI.
  • Silventoinen, Karri; Konttinen, Hanna (2020)
    Obesity has dramatically increased during the last decades and is currently one of the most serious global health problems. We present a hypothesis that obesity is a neuro-behavioral disease having a strong genetic background mediated largely by eating behavior and is sensitive to the macro-environment; we study this hypothesis from the perspective of genetic research. Genetic family and genome-wide-association studies have shown well that body mass index (BMI, kg/m(2)) is a highly heritable and polygenic trait. New genetic variation of BMI emerges after early childhood. Candidate genes of BMI notably express in brain tissue, supporting that this new variation is related to behavior. Obesogenic environments at both childhood family and societal levels reinforce the genetic susceptibility to obesity. Genetic factors have a clear influence on macro-nutrient intake and appetite-related eating behavior traits. Results on the gene-by-diet interactions in obesity are mixed, but emerging evidence suggests that eating behavior traits partly mediate the effect of genes on BMI. However, more rigorous prospective study designs controlling for measurement bias are still needed.
  • Kivimäki, Mika; Batty, G. David; Jokela, Markus (Elsevier Academic Press, 2018)
  • Jokela, Markus; Airaksinen, Jaakko; Virtanen, Marianna; Batty, G. David; Kivimaki, Mika; Hakulinen, Christian (2020)
    Objective We examined how personality traits of the Five Factor Model were related to years of healthy life years lost (mortality and disability) for individuals and the population. Method Participants were 131,195 individuals from 10 cohort studies from Australia, Germany, the United Kingdom, and the United States (n = 43,935 from seven cohort studies for the longitudinal analysis of disability, assessed using scales of Activities of Daily Living). Results Lower Conscientiousness was associated with higher mortality and disability risk, but only when Conscientiousness was below its median level. If the excess risk associated with low Conscientiousness had been absent, population life expectancy would have been 1.3 years longer and disability-free life 1.0 years longer. Lower emotional stability was related to shorter life expectancy, but only among those in the lowest 15% of the distribution, and disability throughout the distribution: if the excess risk associated with low emotional stability had been absent, population life expectancy would have been 0.4 years longer and disability-free life 2.4 years longer. Conclusions Personality traits of low Conscientiousness and low emotional stability are associated with reduced healthy life expectancy of individuals and population.
  • Kahlert, Daniela; Unyi-Reicherz, Annelie; Stratton, Gareth; Larsen, Thomas Meinert; Fogelholm, Mikael; Raben, Anne; Schlicht, Wolfgang (2016)
    Background: Losing excess body weight and preventing weight regain by changing lifestyle is a challenging but promising task to prevent the incidence of type-2 diabetes. To be successful, it is necessary to use evidence-based and theory-driven interventions, which also contribute to the science of behavior modification by providing a deeper understanding of successful intervention components. Objective: To develop a physical activity and dietary behavior modification intervention toolbox (PREMIT) that fulfills current requirements of being theory-driven and evidence-based, comprehensively described and feasible to evaluate. PREMIT is part of an intervention trial, which aims to prevent the onset of type-2 diabetes in pre-diabetics in eight clinical centers across the world by guiding them in changing their physical activity and dietary behavior through a group counseling approach. Methods: The program development took five progressive steps, in line with the Public Health Action Cycle: (1) Summing-up the intervention goal(s), target group and the setting, (2) uncovering the generative psychological mechanisms, (3) identifying behavior change techniques and tools, (4) preparing for evaluation and (5) implementing the intervention and assuring quality. Results: PREMIT is based on a trans -theoretical approach referring to valid behavior modification theories, models and approaches. A major "product" of PREMIT is a matrix, constructed for use by onsite-instructors. The matrix includes objectives, tasks and activities ordered by periods. PREMIT is constructed to help instructors guide participants' behavior change. To ensure high fidelity and adherence of program -implementation across the eight intervention centers standardized operational procedures were defined and "train-the-trainer" workshops were held. In summary PREMIT is a theory-driven, evidence-based program carefully developed to change physical activity and dietary behaviors in pre diabetic people.
  • NCD Risk Factor Collaboration; Bixby, Honor; Auvinen, Juha; Eriksson, Johan G.; Jääskeläinen, Tuija; Laatikainen, Tiina; Järvelin, Marjo-Riitta; Korpelainen, Raija; Puhakka, Soile E.; Sebert, Sylvain; Juolevi, Anne; Kajantie, Eero O.; Koskinen, Seppo; Kuulasmaa, Kari; Lundqvist, Annamari; Peltonen, Markku; Salomaa, Veikko; Tolonen, Hanna K.; Herrala, Sauli; Jokelainen, Jari; Keinänen-Kiukaanniemi, Sirkka; Mursu, Jaakko; Tuomainen, Tomi-Pekka; Virtanen, Jyrki K.; Voutilainen, Ari; Voutilainen, Sari; Kujala, Urho M.; Lehtimäki, Terho; Raitakari, Olli; Salonen, Jukka T.; Saramies, Jouko L.; Uusitalo, Hannu M. T.; Vlasoff, Tiina (2019)
    Body-mass index (BMI) has increased steadily in most countries in parallel with a rise in the proportion of the population who live in cities(.)(1,2) This has led to a widely reported view that urbanization is one of the most important drivers of the global rise in obesity(3-6). Here we use 2,009 population-based studies, with measurements of height and weight in more than 112 million adults, to report national, regional and global trends in mean BMI segregated by place of residence (a rural or urban area) from 1985 to 2017. We show that, contrary to the dominant paradigm, more than 55% of the global rise in mean BMI from 1985 to 2017-and more than 80% in some low- and middle-income regions-was due to increases in BMI in rural areas. This large contribution stems from the fact that, with the exception of women in sub-Saharan Africa, BMI is increasing at the same rate or faster in rural areas than in cities in low- and middle-income regions. These trends have in turn resulted in a closing-and in some countries reversal-of the gap in BMI between urban and rural areas in low- and middle-income countries, especially for women. In high-income and industrialized countries, we noted a persistently higher rural BMI, especially for women. There is an urgent need for an integrated approach to rural nutrition that enhances financial and physical access to healthy foods, to avoid replacing the rural undernutrition disadvantage in poor countries with a more general malnutrition disadvantage that entails excessive consumption of low-quality calories.
  • Carrillo-Larco, R. M.; Aparcana-Granda, D. J.; Mejia, J. R.; Barengo, N. C.; Bernabe-Ortiz, A. (2019)
    Aim To summarize the evidence on diabetes risk scores for Latin American populations. Methods A systematic review was conducted (CRD42019122306) looking for diagnostic and prognostic models for type 2 diabetes mellitus among randomly selected adults in Latin America. Five databases (LILACS, Scopus, MEDLINE, Embase and Global Health) were searched. type 2 diabetes mellitus was defined using at least one blood biomarker and the reports needed to include information on the development and/or validation of a multivariable regression model. Risk of bias was assessed using the PROBAST guidelines. Results Of the 1500 reports identified, 11 were studied in detail and five were included in the qualitative analysis. Two reports were from Mexico, two from Peru and one from Brazil. The number of diabetes cases varied from 48 to 207 in the derivations models, and between 29 and 582 in the validation models. The most common predictors were age, waist circumference and family history of diabetes, and only one study used oral glucose tolerance test as the outcome. The discrimination performance across studies was similar to 70% (range: 66-72%) as per the area under the receiving-operator curve, the highest metric was always the negative predictive value. Sensitivity was always higher than specificity. Conclusion There is no evidence to support the use of one risk score throughout Latin America. The development, validation and implementation of risk scores should be a research and public health priority in Latin America to improve type 2 diabetes mellitus screening and prevention.
  • Lehtinen, Matti; Eriksson, Tiina; Apter, Dan; Hokkanen, Mari; Natunen, Kari; Paavonen, Jorma; Pukkala, Eero; Angelo, Maria-Genalin; Zima, Julia; David, Marie-Pierre; Datta, Sanjoy; Bi, Dan; Struyf, Frank; Dubin, Gary (2016)
    This community-randomized controlled trial was initiated to assess the overall and herd effects of 2 different human papillomavirus (HPV) immunization strategies in over 80,000 girls and boys aged 1215 y in 33 communities in Finland ( NCT00534638). Overall, 14,838 adolescents received HPV-16/18 vaccine (2,440 boys and 12,398 girls) and 17,338 received hepatitis-B virus (HBV) vaccine {9,221 boys and 8,117 girls). In an interim analysis, vaccine safety was assessed by active monitoring and surveillancece via health registry linkage. Active monitoring showed that the HPV-16/18 vaccine has acceptable safety and reactogenicity in boys. In all study participants, the observed incidences (per 100,000 person-years) of serious adverse events (SAEs) possibly, related to vaccination were 54.3 (95% Confidence Interval [CI]: 34.0-82.1) in the HPV-16/18 group and 64.0 (95% CI: 43.2-91.3) in the HBV group. During the follow-up period for this interim analysis, the most common new-onset autoimmune diseases (NOADs; with incidence rate >= 15 per 100,000) in any group based on hospital discharge registry (HILMO) download were ulcerative colitis, juvenile arthritis, celiac disease insulin-dependent diabetes mellitus (IDDM) and Crohn's disease. No increased NOAD incidences were observed in HPV-16/18 vaccine recipients compared to HBV vaccine recipients. In both the SAE possibly related- and HILMO-analyses, a lower incidence of IDDM was observed in HPV-16/18 vaccinees compared to HBV vaccinees (relative risks, 0.26 [95% CI: 0.03-1.24] and 0.16 [95% CI: 0.03-0.55], respectively).
  • Silventoinen, K.; Jelenkovic, A.; Yokoyama, Y.; Sund, R.; Sugawara, M.; Tanaka, M.; Matsumoto, S.; Bogl, L. H.; Maia, J. A.; Hjelmborg, J. v. B.; Aaltonen, S.; Piirtola, M.; Latvala, A.; Calais-Ferreira, L.; Oliveira, V. C.; Ferreira, P. H.; Ji, F.; Ning, F.; Pang, Z.; Ordonana, J. R.; Sanchez-Romera, J. F.; Colodro-Conde, L.; Burt, S. A.; Klump, K. L.; Martin, N. G.; Medland, S. E.; Montgomery, G. W.; Kandler, C.; McAdams, T. A.; Eley, T. C.; Gregory, A. M.; Saudino, K. J.; Dubois, L.; Boivin, M.; Brendgen, M.; Dionne, G.; Vitaro, F.; Tarnoki, A. D.; Tarnoki, D. L.; Haworth, C. M. A.; Plomin, R.; Oncel, S. Y.; Aliev, F.; Medda, E.; Nistico, L.; Toccaceli, V.; Craig, J. M.; Saffery, R.; Siribaddana, S. H.; Hotopf, M.; Sumathipala, A.; Rijsdijk, F.; Jeong, H. -U.; Spector, T.; Mangino, M.; Lachance, G.; Gatz, M.; Butler, D. A.; Gao, W.; Yu, C.; Li, L.; Bayasgalan, G.; Narandalai, D.; Harden, K. P.; Tucker-Drob, E. M.; Christensen, K.; Skytthe, A.; Kyvik, K. O.; Derom, C. A.; Vlietinck, R. F.; Loos, R. J. F.; Cozen, W.; Hwang, A. E.; Mack, T. M.; He, M.; Ding, X.; Silberg, J. L.; Maes, H. H.; Cutler, T. L.; Hopper, J. L.; Magnusson, P. K. E.; Pedersen, N. L.; Dahl Aslan, A. K.; Baker, L. A.; Tuvblad, C.; Bjerregaard-Andersen, M.; Beck-Nielsen, H.; Sodemann, M.; Ullemar, V.; Almqvist, C.; Tan, Q.; Zhang, D.; Swan, G. E.; Krasnow, R.; Jang, K. L.; Knafo-Noam, A.; Mankuta, D.; Abramson, L.; Lichtenstein, P.; Krueger, R. F.; McGue, M.; Pahlen, S.; Tynelius, P.; Rasmussen, F.; Duncan, G. E.; Buchwald, D.; Corley, R. P.; Huibregtse, B. M.; Nelson, T. L.; Whitfield, K. E.; Franz, C. E.; Kremen, W. S.; Lyons, M. J.; Ooki, S.; Brandt, I.; Nilsen, T. S.; Harris, J. R.; Sung, J.; Park, H. A.; Lee, J.; Lee, S. J.; Willemsen, G.; Bartels, M.; Van Beijsterveldt, C. E. M.; Llewellyn, C. H.; Fisher, A.; Rebato, E.; Busjahn, A.; Tomizawa, R.; Inui, F.; Watanabe, M.; Honda, C.; Sakai, N.; Hur, Y. -M.; Sorensen, T. I. A.; Boomsma, D. I.; Kaprio, J. (2019)
    The COllaborative project of Development of Anthropometrical measures in Twins (CODATwins) project is a large international collaborative effort to analyze individual-level phenotype data from twins in multiple cohorts from different environments. The main objective is to study factors that modify genetic and environmental variation of height, body mass index (BMI, kg/m(2)) and size at birth, and additionally to address other research questions such as long-term consequences of birth size. The project started in 2013 and is open to all twin projects in the world having height and weight measures on twins with information on zygosity. Thus far, 54 twin projects from 24 countries have provided individual-level data. The CODATwins database includes 489,981 twin individuals (228,635 complete twin pairs). Since many twin cohorts have collected longitudinal data, there is a total of 1,049,785 height and weight observations. For many cohorts, we also have information on birth weight and length, own smoking behavior and own or parental education. We found that the heritability estimates of height and BMI systematically changed from infancy to old age. Remarkably, only minor differences in the heritability estimates were found across cultural-geographic regions, measurement time and birth cohort for height and BMI. In addition to genetic epidemiological studies, we looked at associations of height and BMI with education, birth weight and smoking status. Within-family analyses examined differences within same-sex and opposite-sex dizygotic twins in birth size and later development. The CODATwins project demonstrates the feasibility and value of international collaboration to address gene-by-exposure interactions that require large sample sizes and address the effects of different exposures across time, geographical regions and socioeconomic status.
  • Masip-Manuel, Guiomar; Silventoinen, Karri; Keski-Rahkonen, Anna; Palviainen, Teemu; Sipilä, Pyry N.; Kaprio, Jaakko; Bogl, Leonie H. (2020)
    Background Obesity susceptibility genes are highly expressed in the brain suggesting that they might exert their influence on body weight through eating-related behaviors. Objectives To examine whether the genetic susceptibility to obesity is mediated by eating behavior patterns. Methods Participants were 3977 twins (33% monozygotic, 56% females), aged 31–37 y, from wave 5 of the FinnTwin16 study. They self-reported their height and weight, eating behaviors (15 items), diet quality, and self-measured their waist circumference (WC). For 1055 twins with genome-wide data, we constructed a polygenic risk score for BMI (PRSBMI) using almost 1 million single nucleotide polymorphisms. We used principal component analyses to identify eating behavior patterns, twin modeling to decompose correlations into genetic and environmental components, and structural equation modeling to test mediation models between the PRSBMI, eating behavior patterns, and obesity measures. Results We identified 4 moderately heritable (h2 = 36–48%) eating behavior patterns labeled “snacking,” “infrequent and unhealthy eating,” “avoidant eating,” and “emotional and external eating.” The highest phenotypic correlation with obesity measures was found for the snacking behavior pattern (r = 0.35 for BMI and r = 0.32 for WC; P < 0.001 for both), largely due to genetic factors in common (bivariate h2 > 70%). The snacking behavior pattern partially mediated the association between the PRSBMI and obesity measures (βindirect = 0.06; 95% CI: 0.02, 0.09; P = 0.002 for BMI; and βindirect = 0.05; 95% CI: 0.02, 0.08; P = 0.003 for WC). Conclusions Eating behavior patterns share a common genetic liability with obesity measures and are moderately heritable. Genetic susceptibility to obesity can be partly mediated by an eating pattern characterized by frequent snacking. Obesity prevention efforts might therefore benefit from focusing on eating behavior change, particularly in genetically susceptible individuals.