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151. Prediction of adult class II/III obesity from childhood BMI: the i3C consortium

Author

Julia Steinberger, Markus Juonala, Ronald J. Prineas, Elaine M. Urbina, Matthew Fenchel, Stephen R. Daniels, David R. Jacobs, Cashell E. Jaquish, Terence Dwyer, Alison Venn, Lydia Bazzano, Nanhua Zhang, Alan R. Sinaiko, Tian Hu, Trudy L. Burns, Justin R. Ryder, Jessica G. Woo, and Olli T. Raitakari

Subjects
Adult, Male, Pediatrics, medicine.medical_specialty, Adolescent, Endocrinology, Diabetes and Metabolism, Medicine (miscellaneous), 030209 endocrinology & metabolism, Overweight, Health outcomes, Adult age, Article, Body Mass Index, Young Adult, 03 medical and health sciences, 0302 clinical medicine, Interquartile range, medicine, Humans, Obesity, Prospective Studies, 030212 general & internal medicine, Child, Preventive healthcare, Nutrition and Dietetics, business.industry, Body Weight, medicine.disease, Cohort, Female, medicine.symptom, business, Childhood age
Abstract

Background and Objectives: Adult class II/III obesity (BMI ≥ 35 kg/m2) has significant adverse health outcomes. Early prevention and treatment are critical, but prospective childhood risk estimates are lacking. This study aimed to define the prospective risk of adult class II/III obesity, using childhood BMI. Methods: Children ages 3–19 years enrolled in cohorts of The International Childhood Cardiovascular Cohort (i3C) Consortium with measured BMI assessments in childhood and adulthood were included. Prospective risk of adult class II/III obesity was modeled based on childhood age, sex, race and BMI. Results: 12 142 individuals (44% male, 85% white) were assessed at median age 14 [Interquartile range, IQR: 11, 16] and 33 [28, 39] years. Class II/III adult obesity developed in 6% of children with normal weight; 29% of children with overweight; 56% of children with obesity; and 80% of children with severe obesity. However, 38% of the 1 440 adults with class II/III obesity (553/1440) were normal weight as children. Prospective risk of adult class II/III obesity varied by age, sex and race within childhood weight status classifications, and is notably higher for girls, black participants, and those in the United States. The risk of class II/III obesity increased with older adult age. Conclusions: Children with obesity or severe obesity have a substantial risk of adult class II/III obesity, and observed prospective risk estimates are now presented by age, sex, race and childhood BMI. Clinical monitoring of children’s BMI for adult class II/III obesity risk may be especially important for females and black Americans., Table of Contents Summary This study developed prospective risk estimates of adult class II/III obesity using childhood BMI, childhood age, sex and race, using longitudinal international data.

Published
2019

152. New evidence from plasma ceramides links apoE polymorphism to greater risk of coronary artery disease in Finnish adults

Author

Juho-Pekka Karjalainen, Miikael Lehtimäki, Nina Hutri-Kähönen, Mika Hilvo, Terho Lehtimäki, Jorma Viikari, Markus Juonala, Olli T. Raitakari, Reijo Laaksonen, Mika Kähönen, Nina Mononen, Dimple Kauhanen, Lääketieteen ja terveysteknologian tiedekunta - Faculty of Medicine and Health Technology, and Tampere University

Subjects
0301 basic medicine, Apolipoprotein E, Coronary Artery Disease, Disease, 030204 cardiovascular system & hematology, Biochemistry, Coronary artery disease, chemistry.chemical_compound, 0302 clinical medicine, Endocrinology, Medicine, Myocardial infarction, dyslipidemias, genes, Finland, apolipoprotein E, education.field_of_study, lipid dysfunction, Low-density lipoprotein, lipids (amino acids, peptides, and proteins), medicine.medical_specialty, Ceramide, Genotype, Biolääketieteet - Biomedicine, Population, QD415-436, Ceramides, Biokemia, solu- ja molekyylibiologia - Biochemistry, cell and molecular biology, 03 medical and health sciences, Apolipoproteins E, Internal medicine, Humans, education, Triglycerides, Dyslipidemias, Polymorphism, Genetic, Apolipoprotein A-I, business.industry, Cholesterol, HDL, Cholesterol, LDL, Cell Biology, Atherosclerosis, medicine.disease, Metabolism, 030104 developmental biology, Genes, low-density lipoprotein, chemistry, Lipidomics, atherosclerosis, Patient-Oriented and Epidemiological Research, business, Lipid dysfunction, Lipoprotein
Abstract

apoE, a key regulator of plasma lipids, mediates altered functionalities in lipoprotein metabolism and thus affects the risk of coronary artery disease (CAD). The significance of different apoE polymorphisms remains unclear; although the ε4 allele is clearly associated with increased cholesterol levels (which inform CAD risk), direct studies about apoE polymorphisms on CAD risk and development have yielded controversial results. Furthermore, certain species of ceramides—complex lipids abundant in plasma LDL—are markers of increased risk of myocardial infarction and cardiovascular death. Using a high-throughput MS approach, we quantified 30 molecular plasma ceramide species from a cohort of 2,160 apoE-genotyped (rs7412, rs429358) young adults enrolled in the population-based Cardiovascular Risk in Young Finns Study. We then searched this lipidome data set to identify new indications of pathways influenced by apoE polymorphisms and possibly related to CAD risk. This approach revealed a previously unreported association between apoE polymorphism and a consistently documented high-risk CAD marker, Cer(d18:1/16:0). Compared with the apoE ε3/3 reference group, plasma levels of apoE ε4 were elevated and those of apoE ε2 were lowered in all subjects without evidence of apoE-by-sex interactions. apoE associated with seven ceramides that are connected to atherogenically potent macrophages and/or lipoprotein particles; these associations could indicate a plausible linkage between apoE polymorphism and ceramide metabolism, leading to adverse plasma LDL metabolism and atherogenesis. In conclusion, new evidence from plasma ceramides links apoE polymorphism with an increased risk of CAD and extends our understanding of the role of apoE in health and disease.

Published
2019

153. Variants in the fetal genome near pro-inflammatory cytokine genes on 2q13 associate with gestational duration

Author

Maria Carolina Borges, M. Geoffrey Hayes, Ke Hao, Carol A. Wang, Marjo-Riitta Järvelin, Niina Pitkänen, Ilkka Kalliala, Mariona Bustamante, Olli T. Raitakari, Bridget A. Knight, Robin N Beaumont, Matthew T. Weirauch, Line Skotte, Matthias Wielscher, Mark I. McCarthy, Klaus Bønnelykke, Vincent W. V. Jaddoe, Elina Hyppönen, Ole Mors, Tarunveer S. Ahluwalia, Thomas Werge, Frank Geller, Jonathan P. Bradfield, Vivek Appadurai, Kristin Skogstrand, Merete Nordentoft, Suzanne Vogelezang, Preben Bo Mortensen, Xueping Liu, Daniel Miller, Hakon Hakonarson, João Fadista, Pål R. Njølstad, Leah C. Kottyan, Wesley K. Thompson, Bruce Bedell, Katja Pahkala, Stefan Johansson, Dorte Helenius, Louis J. Muglia, Janine F. Felix, Rachel M. Freathy, Heather A. Boyd, Bjarke Feenstra, Ge Zhang, Anubha Mahajan, Alfonso Buil, Bo Jacobsson, Martine Vrijheid, Frederick T.J. Lin, William L. Lowe, Mads Melbye, Ron Nudel, Denise M. Scholtens, Julius Juodakis, Shouneng Peng, Christine Power, Andrew J. Schork, Jeffrey C. Murray, David M. Hougaard, Craig E. Pennell, Øyvind Helgeland, Struan F.A. Grant, Kelli K. Ryckman, Mary L. Marazita, Xiaoting Chen, Jonas Bacelis, Anders D. Børglum, Debbie A Lawlor, Hans Bisgaard, Robert M. Rossi, Fernando Rivadeneira, Leo-Pekka Lyytikäinen, Rebecca K. Vinding, Department of Obstetrics and Gynecology, HUS Gynecology and Obstetrics, Clinicum, Helsinki University Hospital Area, Epidemiology, Internal Medicine, Pediatrics, Erasmus MC other, Liu, Xueping, Helenius, Dorte, Skotte, Line, Beaumont, Robin N, Hyppönen, Elina, Feenstra, Bjarke, and UNIVERSITY OF OULU

Subjects
0301 basic medicine, LD SCORE REGRESSION, General Physics and Astronomy, Genome-wide association study, 02 engineering and technology, Reproductive health and childbirth, Bioinformatics, Low Birth Weight and Health of the Newborn, Genome-wide association studies, 3123 Gynaecology and paediatrics, Pregnancy, Genotype, Infant Mortality, Genetics research, 2.1 Biological and endogenous factors, WIDE ASSOCIATION, GWAS, FUNCTIONAL VARIATION, Aetiology, lcsh:Science, Pediatric, Multidisciplinary, Genome, Gestational age, Single Nucleotide, 021001 nanoscience & nanotechnology, 3. Good health, Multidisciplinary Sciences, Chromosomes, Human, Pair 2, Pair 2, Gestation, Science & Technology - Other Topics, Premature Birth, Cytokines, Female, 0210 nano-technology, Human, Reproductive signs and symptoms, EXPRESSION, PRETERM BIRTH, Science, Reproductive biology, Locus (genetics), Gestational Age, Biology, Polymorphism, Single Nucleotide, SEQUENCE, Article, General Biochemistry, Genetics and Molecular Biology, Chromosomes, 03 medical and health sciences, AGE, Fetus, Preterm, medicine, Genetics, SNP, Humans, Polymorphism, Science & Technology, Genome, Human, Human Genome, Infant, Newborn, Infant, General Chemistry, Perinatal Period - Conditions Originating in Perinatal Period, medicine.disease, Newborn, 030104 developmental biology, Good Health and Well Being, lcsh:Q, WEIGHT, 3111 Biomedicine, HAPLOTYPES, Genome-Wide Association Study
Abstract

The duration of pregnancy is influenced by fetal and maternal genetic and non-genetic factors. Here we report a fetal genome-wide association meta-analysis of gestational duration, and early preterm, preterm, and postterm birth in 84,689 infants. One locus on chromosome 2q13 is associated with gestational duration; the association is replicated in 9,291 additional infants (combined P = 3.96 × 10−14). Analysis of 15,588 mother-child pairs shows that the association is driven by fetal rather than maternal genotype. Functional experiments show that the lead SNP, rs7594852, alters the binding of the HIC1 transcriptional repressor. Genes at the locus include several interleukin 1 family members with roles in pro-inflammatory pathways that are central to the process of parturition. Further understanding of the underlying mechanisms will be of great public health importance, since giving birth either before or after the window of term gestation is associated with increased morbidity and mortality., Gestational duration depends on both maternal and fetal genetic influences. Here, the authors perform a fetal genome-wide association meta-analysis and find that a locus on 2q13 is associated with pregnancy duration and further show that the lead SNP rs7594852 changes the binding properties of transcriptional repressor HIC1.

Published
2019

154. Adverse childhood environment and self-reported sleep in adulthood: The Young Finns Study

Author

Olli T. Raitakari, Laura Pulkki-Råback, Päivi Merjonen, Jari Lipsanen, Liisa Keltikangas-Järvinen, Tom Rosenström, Mirka Hintsanen, Emma Talvitie, Christian Hakulinen, Terho Lehtimäki, Marko Elovainio, Tampere University, Department of Clinical Chemistry, and Clinical Medicine

Subjects
Adult, Male, Sleep Wake Disorders, Adolescent, 515 Psychology, Health Behavior, Population, Cumulative Exposure, Affect (psychology), 03 medical and health sciences, Risk Factors, Insomnia, medicine, Humans, Prospective Studies, Child, education, Socioeconomic status, Applied Psychology, education.field_of_study, 030505 public health, business.industry, Stressor, Middle Aged, Psychiatry and Mental health, Child, Preschool, Female, 3111 Biomedicine, Self Report, medicine.symptom, Sleep, 0305 other medical science, business, Body mass index, Clinical psychology
Abstract

Objective To determine the association between cumulative exposure to parent-reported childhood adversities and self-reported adulthood suboptimal sleep. Methods Participants (n = 1,038; 57.4% women) were drawn from the prospective population-based Young Finns Study. Childhood adversities were assessed in 1980 among 3- to- 18-year-olds, while components of suboptimal sleep were measured 27 years later. Cumulative childhood adversities included factors from four domains: stressful life events, adverse parental health behaviors, adverse emotional environment, and low socioeconomic status. Logistic, linear, and ordinal regression analyses were conducted to examine associations between cumulative exposure and self-reported sleep duration, sleep deficiency, and sleep problems, respectively. Multiple imputations were applied to correct for participants lost to follow-up and for missing values (resulting in n = 3,559) and the aforementioned analyses were rerun. Results More adverse parental health behaviors (OR = 1.19, CI 95% [1.02-1.38], p = .03) and combined childhood adversities (OR = 1.10, CI 95% [1.02-1.19], p = .02) were associated with sleeping less than six hours. Neither association withstood adjustment for adulthood health or socioeconomic status or both, nor for attrition bias. No associations were found between adverse childhood environments and sleep deficiency or problems. Conclusions The accumulation of more typical childhood adversities might not persistently affect self-reported sleep duration, sleep deficiency or sleep problems in adulthood. However, this study is among the first to assess the effects of the accumulation of everyday stressors on sleep and therefore, more research is warranted on everyday adversities for more definitive conclusions. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

Published
2019

155. Relation of Blood Pressure in Childhood to Self-Reported Hypertension in Adulthood

Author

Trudy L. Burns, David R. Jacobs, Elaine M. Urbina, Stephen R. Daniels, Jessica G. Woo, Olli T. Raitakari, Philip R. Khoury, Terrence Dwyer, Tian Hu, Julia Steinberger, Ronald J. Prineas, Alan R. Sinaiko, Alison Venn, Lydia Bazzano, and Markus Juonala

Subjects
Pediatrics, medicine.medical_specialty, Percentile, business.industry, Retrospective cohort study, 030204 cardiovascular system & hematology, Logistic regression, medicine.disease, Obesity, 03 medical and health sciences, 0302 clinical medicine, Blood pressure, Internal Medicine, medicine, 030212 general & internal medicine, Young adult, Risk factor, business, Body mass index
Abstract

Blood pressure (BP) tracking (maintaining a BP percentile) across life is not well defined but is important in predicting which children will become hypertensive adults. We computed BP tracking in subjects with BP measured in childhood and adulthood and performed logistic regression to determine the ability of childhood BP to predict adult hypertension (N=5035, 46.7 years, 74.2% white, 17.7% black; 39.6% male). Prevalence of hypertension was 29%. Correlations between systolic BP for child and adolescent were r =0.48; for adolescent and young adult were r =0.40, and for child and young adult were r =0.24 (all P P P 2

Published
2019

156. Socioeconomic position and intergenerational associations of ideal health behaviors

Author

Markus Juonala, Markus Jokela, Kaisla Komulainen, Liisa Keltikangas-Järvinen, Katja Pahkala, Tuija Tammelin, Laura Pulkki-Råback, Mika Kähönen, Tomi T. Laitinen, Olli T. Raitakari, Murray A. Mittleman, Marko Elovainio, Department of Psychology and Logopedics, University of Helsinki, and Psychosocial factors and health

Subjects
Male, Health Knowledge, Attitudes, Practice, family, Socioeconomic position, Social Determinants of Health, Epidemiology, Health Status, CHILDHOOD, ADULTHOOD, Disease, 030204 cardiovascular system & hematology, DISEASE, Body Mass Index, Developmental psychology, TRACKING, 0302 clinical medicine, health behavior, Risk Factors, CARDIOVASCULAR RISK-FACTORS, Medicine, Prospective Studies, 030212 general & internal medicine, Finland, Smoking, EDUCATION, 16. Peace & justice, Cardiovascular Diseases, Intergenerational Relations, Income, Educational Status, Cohort studies, Female, PSYCHOSOCIAL FACTORS, Health behavior, Cardiology and Cardiovascular Medicine, Cohort study, Adult, TRANSMISSION, 515 Psychology, Cardiovascular health, Social class, Risk Assessment, 03 medical and health sciences, Humans, Healthy Lifestyle, Occupations, Exercise, Ideal (set theory), business.industry, Protective Factors, Diet, PHYSICAL-ACTIVITY, 3121 General medicine, internal medicine and other clinical medicine, Tracking (education), social class, PRIMARY PREVENTION, business, Risk Reduction Behavior
Abstract

Background Promoting ideal cardiovascular health behaviors is an objective of the American Heart Association 2020 goals. We hypothesized that ideal health behaviors of parents are associated with health behaviors of their adult offspring, and that higher socioeconomic position in either generation enhances intergenerational associations of ideal health behaviors. Design Prospective cohort study. Methods We included 1856 Young Finns Study participants who had repeated measurements of socioeconomic position (education, income, occupation), smoking status, body mass index, physical activity and diet from 2001, 2007 and 2011, and data on parental socioeconomic position and health behaviors from 1980. We calculated the total number of ideal behaviors in both generations using American Heart Association definitions. Intergenerational associations were examined using ordinal and linear multilevel regression with random intercepts, in which each participant contributed one, two or three measurements of adult health behaviors (2001, 2007, 2011). All analyses were adjusted for offspring sex, birth year, age, parental education and single parenthood. Results Overall, parental ideal health behaviors were associated with ideal behaviors among offspring (odds ratio (OR) 1.28, 95% confidence interval 1.17, 1.39). Furthermore, ORs for these intergenerational associations were greater among offspring whose parents or who themselves had higher educational attainment (OR 1.56 for high vs. OR 1.19 for low parental education; P = 0.01 for interaction, OR 1.32 for high vs. OR 1.04 for low offspring education; P = 0.02 for interaction). Similar trends were seen with parental income and offspring occupation. Results from linear regression analyses were similar. Conclusions These prospective data suggest higher socioeconomic position in parents or in their adult offspring strengthens the intergenerational continuum of ideal cardiovascular health behaviors.

Published
2019

157. New genetic signals for lung function highlight pathways and chronic obstructive pulmonary disease associations across multiple ancestries

Author

Phuwanat Sakornsakolpat, James F. Wilson, María Soler Artigas, Beate Stubbe, Nicholas J. Wareham, James D. Crapo, Victoria E. Jackson, Eleftheria Zeggini, Olga G. Troyanskaya, Medea Imboden, A. Mesut Erzurumluoglu, Adam S. Butterworth, Carl A. Melbourne, Ian Sayers, Lars Lind, Stefan Weiss, Margaret M. Parker, Timmers Prhj, Edwin K. Silverman, John C. Whittaker, Ian P. Hall, Ozren Polasek, Mika Kähönen, Katherine A. Fawcett, Anna Hansell, Liming Li, David J. Porteous, Louise V. Wain, Robert A. Scott, Richard Packer, Richard J. Allen, Robin G Walters, Anna L. Guyatt, Terho Lehtimäki, Nicole Probst-Hensch, Shona M. Kerr, Christian Gieger, Matthias Wielscher, Rajesh Rawal, Jing Hua Zhao, John E. Hokanson, Holger Schulz, Nicola F. Reeve, Claudia Langenberg, Ke Hao, Corry-Anke Brandsma, Megan L. Paynton, Vitart, Dmitry Prokopenko, Jennie Hui, Eugene R. Bleecker, Ma'en Obeidat, John Danesh, Ralf Ewert, Benjamin B. Sun, Frank Dudbridge, Jian Zhou, Brian D. Hobbs, Blair H. Smith, Don D. Sin, Dawn L. DeMeo, Joseph C. Maranville, Ida Surakka, Alison Catherine Murray, Nicholas Locantore, Katherine A. Kentistou, Terri H. Beaty, Igor Rudan, Kuang Lin, Amund Gulsvik, Ian J. Deary, Ruth Tal-Singer, Kijoung Song, David C. Nickle, Michael H. Cho, Jian'an Luan, Joshua D. Hoffman, Georg Homuth, Zhengming Chen, Dandi Qiao, Heiko Runz, Per Bakke, Chiara Batini, Caroline Hayward, Stefan Karrasch, Alan James, Andrew P. Morris, Prescott G. Woodruff, Laura M Yerges Armstrong, David Sparrow, Ulf Gyllensten, James P. Cook, Jonathan Marten, Olli T. Raitakari, Nick Shrine, Deborah A. Meyers, Tobin, Ruth Boxall, Marjo-Riitta Järvelin, David P. Strachan, Sarah E. Harris, Philippe Joubert, Stefan Enroth, Xingnan Li, van den Berge M, Anubha Mahajan, Yohan Bossé, Peter K. Joshi, Shrine, Nick [0000-0003-3641-4371], Guyatt, Anna L [0000-0003-1860-6337], Hobbs, Brian D [0000-0001-9564-0745], Sakornsakolpat, Phuwanat [0000-0002-4308-0974], Obeidat, Ma'en [0000-0002-5443-2752], Weiss, Stefan [0000-0002-3553-4315], Kentistou, Katherine A [0000-0002-5816-664X], Sun, Benjamin B [0000-0001-6347-2281], Enroth, Stefan [0000-0002-5056-9137], Vitart, Veronique [0000-0002-4991-3797], Allen, Richard J [0000-0002-8450-3056], Beaty, Terri H [0000-0002-7644-1705], Bossé, Yohan [0000-0002-3067-3711], Joshi, Peter K [0000-0002-6361-5059], Mahajan, Anubha [0000-0001-5585-3420], Murray, Alison [0000-0003-4915-4847], Porteous, David J [0000-0003-1249-6106], Sayers, Ian [0000-0001-5601-5410], Smith, Blair H [0000-0002-5362-9430], Tal-Singer, Ruth [0000-0002-5275-8062], Timmers, Paul RHJ [0000-0002-5197-1267], Troyanskaya, Olga G [0000-0002-5676-5737], Rudan, Igor [0000-0001-6993-6884], Wilson, James F [0000-0001-5751-9178], Zeggini, Eleftheria [0000-0003-4238-659X], Hayward, Caroline [0000-0002-9405-9550], Morris, Andrew P [0000-0002-6805-6014], Butterworth, Adam S [0000-0002-6915-9015], Walters, Robin G [0000-0002-9179-0321], Cho, Michael H [0000-0002-4907-1657], Strachan, David P [0000-0001-7854-1366], Tobin, Martin D [0000-0002-3596-7874], Wain, Louise V [0000-0003-4951-1867], Apollo - University of Cambridge Repository, Institute for Molecular Medicine Finland, Groningen Research Institute for Asthma and COPD (GRIAC), UNIVERSITY OF OULU, and Commission of the European Communities

Subjects
Male, Smoking/genetics, LOCI, Genome-wide association study, VARIANTS, Bioinformatics, Genome-wide association studies, Pulmonary Disease, Chronic Obstructive, 0302 clinical medicine, Polymorphism (computer science), Risk Factors, GWAS, GENOME-WIDE ASSOCIATION, HERITABILITY, COPD, Lung, 11 Medical and Health Sciences, Genetics & Heredity, Aged, 80 and over, 0303 health sciences, Genetic Predisposition to Disease/genetics, Smoking, 1184 Genetics, developmental biology, physiology, Middle Aged, Polymorphism, Single Nucleotide/genetics, 3. Good health, medicine.anatomical_structure, Meta-analysis, Genome-Wide Association Study/methods, Medical genetics, Female, Life Sciences & Biomedicine, medicine.medical_specialty, Understanding Society Scientific Group, Biology, Polymorphism, Single Nucleotide, Article, 03 medical and health sciences, Genetics, medicine, Humans, Genetic Predisposition to Disease, 030304 developmental biology, Genetic association, Aged, Respiratory tract diseases, Science & Technology, Case-control study, Lung/physiopathology, 06 Biological Sciences, medicine.disease, Pulmonary Disease, Chronic Obstructive/genetics, respiratory tract diseases, Case-Control Studies, 3111 Biomedicine, 030217 neurology & neurosurgery, Developmental Biology, Genome-Wide Association Study
Abstract

Reduced lung function predicts mortality and is key to the diagnosis of chronic obstructive pulmonary disease (COPD). In a genome-wide association study in 400,102 individuals of European ancestry, we define 279 lung function signals, 139 of which are new. In combination, these variants strongly predict COPD in independent patient populations. Furthermore, the combined effect of these variants showed generalizability across smokers and never-smokers, and across ancestral groups. We highlight biological pathways, known and potential drug targets for COPD and, in phenome-wide association studies, autoimmune-related and other pleiotropic effects of lung function associated variants. This new genetic evidence has potential to improve future preventive and therapeutic strategies for COPD., Editorial summary: A genome-wide association study in over 400,000 individuals identifies 139 new signals for lung function. These variants can predict chronic obstructive pulmonary disease in independent, trans-ethnic cohorts.

Published
2019

158. Utility of Different Blood Pressure Measurement Components in Childhood to Predict Adult Carotid Intima-Media Thickness

Author

Markus Juonala, Jessica G. Woo, Olli T. Raitakari, Alison Venn, Lydia Bazzano, Costan G. Magnussen, Stephen R. Daniels, Alan R. Sinaiko, Ronald J. Prineas, Matthew A. Sabin, Jorma Viikari, Julia Steinberger, Juha Koskinen, Janina Petkeviciene, David R. Jacobs, Terence Dwyer, Indrė Čeponienė, Nina Hutri-Kähönen, Wei Chen, Elaine M. Urbina, Trudy L. Burns, and HYKS erva

Subjects
medicine.medical_specialty, Mean arterial pressure, Percentile, pediatrics, Diastole, CHILDREN, DETERMINANTS, 030204 cardiovascular system & hematology, SUBCLINICAL ATHEROSCLEROSIS, TRACKING, 03 medical and health sciences, AGE, 0302 clinical medicine, 3123 Gynaecology and paediatrics, 030225 pediatrics, Internal medicine, CARDIOVASCULAR RISK-FACTORS, Internal Medicine, medicine, Systole, ASSOCIATIONS, INSULIN-RESISTANCE, business.industry, blood pressure, Odds ratio, Pulse pressure, Blood pressure, Intima-media thickness, ADOLESCENCE, 3121 General medicine, internal medicine and other clinical medicine, YOUNG FINNS, Cardiology, epidemiology, arterial pressure, atherosclerosis, business
Abstract

Childhood blood pressure (BP) levels predict adult subclinical atherosclerosis. However, the best childhood BP component for prediction has not been determined. This study comprised 5925 participants aged 3 to 18 years from 6 cohorts who were followed into adulthood (mean follow-up 25.8±6.2 years). Childhood BP was measured by using a standard mercury sphygmomanometer in all cohorts. Study-specific carotid intima-media thickness ≥90th percentile was used to define subclinical atherosclerosis. Per SD change in the predictor, childhood systolic BP (SBP; age- and sex-adjusted odds ratio [95% CI], 1.24 [1.13–1.37]), mean arterial pressure (1.10 [1.07–1.13]), and pulse pressure (1.15 [1.05–1.27]) were associated with increased adulthood intima-media thickness. In age- and sex-adjusted analyses, area under the receiver operating characteristic curves for SBP ( C value [95% CI], 0.677 [0.657–0.704]) showed significantly improved prediction compared with diastolic BP (0.669 [0.646–0.693], P =0.006) or mean arterial pressure (0.674 [0.653–0.699], P =0.01). Pulse pressure provided a C value that was not different from SBP (0.676 [0.653–0.699], P =0.16). Combining different BP components did not improve prediction over SBP measurement alone. Based on the associations with adult carotid intima-media thickness, cut points for elevated SBP were 105 mm Hg for 3- to 6-year-old boys, 108 mm Hg for 3- to 6-year-old girls, 108 mm Hg for 7- to 12-year-old boys, 106 mm Hg for 7- to 12-year-old girls, 123 mm Hg for 13- to 18-year-old boys, and 115 mm Hg for 13- to 18-year-old girls. Our analyses suggest that several childhood BP measurement components are related to adulthood carotid intima-media thickness. Of these, SBP provided the best predictive ability.

Published
2019

159. Youth and Long-Term Dietary Calcium Intake With Risk of Impaired Glucose Metabolism and Type 2 Diabetes in Adulthood

Author

Markus Juonala, Costan G. Magnussen, Niina Pitkänen, Feitong Wu, Jorma Viikari, Nina Hutri-Kähönen, Olli T. Raitakari, Antti Jula, Marie-Jeanne Buscot, Tapani Rönnemaa, Katja Pahkala, Mika Kähönen, Matthew A. Sabin, Tomi Laitinen, and Terho Lehtimäki

Subjects
Adult, Blood Glucose, Male, medicine.medical_specialty, Adolescent, endocrine system diseases, Endocrinology, Diabetes and Metabolism, Clinical Biochemistry, Blood sugar, 030209 endocrinology & metabolism, Context (language use), Type 2 diabetes, Biochemistry, Prediabetic State, Young Adult, 03 medical and health sciences, 0302 clinical medicine, Endocrinology, Risk Factors, Diabetes mellitus, Internal medicine, medicine, Humans, Longitudinal Studies, Prospective Studies, 030212 general & internal medicine, Young adult, Child, Finland, 2. Zero hunger, business.industry, Incidence, Biochemistry (medical), nutritional and metabolic diseases, Fasting, Feeding Behavior, Middle Aged, Impaired fasting glucose, medicine.disease, Obesity, Calcium, Dietary, Diabetes Mellitus, Type 2, Child, Preschool, Female, business, Body mass index
Abstract

Context To the best of our knowledge, no previous studies have examined the role of youth calcium intake in the development of impaired glucose metabolism, especially those with long-term high calcium intake. Objectives To examine whether youth and long-term (between youth and adulthood) dietary calcium intake is associated with adult impaired glucose metabolism and type 2 diabetes (T2D). Design, setting, and participants The Cardiovascular Risk in Young Finns Study is a 31-year prospective cohort study (n = 1134; age, 3 to 18 years at baseline). Exposures Dietary calcium intake was assessed at baseline (1980) and adult follow-up visits (2001, 2007, and 2011). Long-term (mean between youth and adulthood) dietary calcium intake was calculated. Main outcome measures Adult impaired fasting glucose (IFG) and T2D. Results We found no evidence for nonlinear associations between calcium intake and IFG or T2D among females and males (all P for nonlinearity > 0.05). Higher youth and long-term dietary calcium intake was not associated with the risk of IFG or T2D among females or males after adjustment for confounders, including youth and adult body mass index. Conclusions Youth or long-term dietary calcium intake is not associated with adult risk of developing impaired glucose metabolism or T2D.

Published
2019

160. Genome-wide meta-analysis of macronutrient intake of 91,114 European ancestry participants from the cohorts for heart and aging research in genomic epidemiology consortium

Author

Panos Deloukas, Christina-Alexandra Schulz, Caren E. Smith, Lu Qi, Mary F. Feitosa, Melissa E. Garcia, Natalia Pervjakova, Denise K. Houston, Michael A. Province, Stavroula Kanoni, Torben Hansen, Jean Shin, Lynda M. Rose, Oscar H. Franco, Yongmei Liu, Trudy Voortman, Marie-Claude Vohl, Luigi Ferrucci, Chloé Sarnowski, Paul S. de Vries, Jose C. Florez, John C. Lieske, Louis Pérusse, Misa Graff, Jian'an Luan, Nicola M. McKeown, Felix R. Day, L. Adrienne Cupples, Qibin Qi, Frank J. A. van Rooij, Robert A. Scott, Josée Dupuis, Stephen S. Rich, Jorma Viikari, Tarunveer S. Ahluwalia, Leo-Pekka Lyytikäinen, Paul M. Ridker, Tomáš Paus, Stephen Turner, Harri Rissanen, Audrey Y. Chu, Albert Hofman, Olli T. Raitakari, Paul Knekt, Daniel I. Chasman, Nita G. Forouhi, Vera Mikkilä, Toshiko Tanaka, Mika Kähönen, George Dedoussis, Minjung Kho, Yun J. Sung, Anne E. Justice, Julius S. Ngwa, Ani Manichaikul, M. Carola Zillikens, Jordi Merino, Dena G. Hernandez, Rozenn N. Lemaitre, Tao Huang, Sharon L.R. Kardia, Jing Hua Zhao, Stefania Bandinelli, Veikko Salomaa, Arne Astrup, Wei Zhao, David S. Siscovick, John Blangero, Zdenka Pausova, Dabeeru C. Rao, Oluf Pedersen, Craig E. Pennell, Wendy H. Oddy, Jose M. Ordovas, Jessica C. Kiefte-de Jong, Marju Orho-Melander, Hassan S. Dashti, Satu Männistö, Tuomo Rankinen, Constantina Papoutsakis, Sherly X. Li, Antti Jula, Kari E. North, Thorkild I. A. Sørensen, André G. Uitterlinden, Alexis C. Frazier-Wood, Nicholas J. Wareham, Ulrika Ericson, Markus Perola, Ioanna P. Kalafati, Renée de Mutsert, Jinyan Huang, Ruifang Li-Gao, Claudia Langenberg, Mike A. Nalls, Olivia Li, Joanne E. Curran, Dennis O. Mook-Kanamori, Niina Eklund, Jerome I. Rotter, Angelo Tremblay, Claude Bouchard, Jennifer A. Smith, Terho Lehtimäki, Mary K. Wojczynski, Carol A. Wang, Epidemiology, Internal Medicine, Zhao, Jing Hua [0000-0003-4930-3582], Luan, Jian'an [0000-0003-3137-6337], Day, Felix [0000-0003-3789-7651], Langenberg, Claudia [0000-0002-5017-7344], Wareham, Nicholas [0000-0003-1422-2993], Forouhi, Nita [0000-0002-5041-248X], and Apollo - University of Cambridge Repository

Subjects
0301 basic medicine, Male, medicine.medical_specialty, Aging, Calorie, Genotype, Heart Diseases, Receptors, Retinoic Acid, Alpha-Ketoglutarate-Dependent Dioxygenase FTO, Locus (genetics), Genome-wide association study, Biology, Polymorphism, Single Nucleotide, Article, White People, Cohort Studies, 03 medical and health sciences, Cellular and Molecular Neuroscience, 0302 clinical medicine, Genetic variation, medicine, Humans, Genetic Predisposition to Disease, Obesity, Molecular Biology, Aged, 2. Zero hunger, Genetics, Family aggregation, Membrane Proteins, Genomics, Nutrients, Middle Aged, medicine.disease, 3. Good health, Fibroblast Growth Factors, Psychiatry and Mental health, 030104 developmental biology, Genetic Loci, Meta-analysis, Medical genetics, Female, Energy Intake, 030217 neurology & neurosurgery, Genome-Wide Association Study
Abstract

Macronutrient intake, the proportion of calories consumed from carbohydrate, fat, and protein, is an important risk factor for metabolic diseases with significant familial aggregation. Previous studies have identified two genetic loci for macronutrient intake, but incomplete coverage of genetic variation and modest sample sizes have hindered the discovery of additional loci. Here, we expanded the genetic landscape of macronutrient intake, identifying 12 suggestively significant loci (P < 1 × 10(−6)) associated with intake of any macronutrient in 91,114 European ancestry participants. Four loci replicated and reached genome-wide significance in a combined meta-analysis including 123,659 European descent participants, unraveling two novel loci; a common variant in RARB locus for carbohydrate intake and a rare variant in DRAM1 locus for protein intake, and corroborating earlier FGF21 and FTO findings. In additional analysis of 144,770 participants from the UK Biobank, all identified associations from the two-stage analysis were confirmed except for DRAM1. Identified loci might have implications in brain and adipose tissue biology and have clinical impact in obesity-related phenotypes. Our findings provide new insight into biological functions related to macronutrient intake.

Published
2019

161. Multiancestry Genome-Wide Association Study of Lipid Levels Incorporating Gene-Alcohol Interactions

Author

Alexandre C. Pereira, Jie Yao, Makoto Hirata, Ozren Polasek, Dragana Vuckovic, Mariaelisa Graff, Jing Hua Zhao, Michael R. Brown, Xuan Deng, Barbara V. Howard, Vilmundur Gudnason, Tuomo Rankinen, Yuan Shi, Timo A. Lakka, Ulrich Broeckel, Anuradhani Kasturiratne, Eric Boerwinkle, Charles Kooperberg, Hugues Aschard, Stephen S. Rich, Pamela J. Schreiner, Dan E. Arking, Hans J. Grabe, Ilaria Gandin, Mario Sims, Carl D. Langefeld, Yii-Der Ida Chen, Meian He, W. James Gauderman, Bruce M. Psaty, Kent D. Taylor, Tõnu Esko, Olli T. Raitakari, Saima Afaq, Maik Pietzner, Federica Laguzzi, Dennis O. Mook-Kanamori, Gregory P. Wilson, Xiuqing Guo, Jaspal S. Kooner, David R. Jacobs, Yajuan Wang, Raha Pazoki, Wei Zhao, Andres Metspalu, Mary F. Feitosa, Jost B. Jonas, Tin Aung, Tamara B. Harris, Karin Leander, Nancy L. Pedersen, Charles B. Eaton, Sharon L.R. Kardia, Bernardo L. Horta, Candace M. Kammerer, Terrence Forrester, Alexander P. Reiner, Paul W. Franks, Tanika N. Kelly, Igor Rudan, Ruben N. Eppinga, Melissa A. Richard, Colin A. McKenzie, Christine Williams, Christian Gieger, Joseph H. Lee, Brigitte Kühnel, Christopher P. Nelson, Wen Bin Wei, Antonietta Robino, Anne U. Jackson, E. Shyong Tai, Alisa K. Manning, Lisa R. Yanek, Paul Elliott, Lynne E. Wagenknecht, Ananda R. Wickremasinghe, José Eduardo Krieger, Peter S. Sever, Nora Franceschini, André G. Uitterlinden, Paul M. Ridker, Yun J. Sung, Karen L. Mohlke, Thomas H. Mosley, Nilesh J. Samani, Patricia B. Munroe, Jennifer A. Smith, John M. C. Connell, H. Janaka de Silva, Nicholas Y. Q. Tan, Jian'an Luan, Jennifer E. Huffman, Anna F. Dominiczak, Carsten Oliver Schmidt, Christie M. Ballantyne, Peter J. van der Most, Anuj Goel, Jerome I. Rotter, Amy R. Bentley, Lihua Wang, Rajkumar Dorajoo, Lenore J. Launer, Yechiel Friedlander, Mickaël Canouil, Traci M. Bartz, Thomas Meitinger, Robert A. Scott, Mike A. Nalls, Xueling Sim, Sarah E. Harris, Michael A. Province, Chew-Kiat Heng, Zhe Wang, Norihiro Kato, Evangelos Evangelou, Philippe Froguel, Virginia Fisher, Leslie J. Raffel, Renée de Mutsert, Michele K. Evans, Brenda W.J.H. Penninx, Yih Chung Tham, Tin Louie, Nana Matoba, Lawrence F. Bielak, Andrea R. V. R. Horimoto, Jingmin Liu, Lynda M. Rose, Nona Sotoodehnia, Daniel I. Chasman, Jasmin Divers, John M. Starr, Patricia A. Peyser, Ervin R. Fox, Barry I. Freedman, Megan L. Grove, Jeffrey R. O'Connell, Rob M. van Dam, Michiaki Kubo, Jessica D. Faul, Fang-Chi Hsu, Yize Li, Ilja M. Nolte, Caroline Hayward, Paolo Gasparini, Chiea Chuen Khor, Changwei Li, Xu Chen, James E. Hixson, Patrik K. E. Magnusson, John C. Chambers, Yoichiro Kamatani, Sami Heikkinen, M. Abdullah Said, Martin Farrall, Alena Stančáková, Konstantin Strauch, Albert V. Smith, Yik Ying Teo, Bamidele O. Tayo, Tamar Sofer, Caizheng Yu, Maris Alver, Oscar H. Franco, Yongmei Liu, Ioanna Ntalla, Myriam Fornage, W. Craig Johnson, Dina Vojinovic, William R. Scott, David R. Weir, Yanick Hagemeijer, Raymond Noordam, Mathilde Boissel, Cornelia M. van Duijn, Karen Schwander, Jingzhong Ding, James Scott, Diana van Heemst, Ching-Yu Cheng, Woon-Puay Koh, Jianjun Liu, Kenneth J. Mukamal, Blair H. Smith, Claude Bouchard, Claudia Langenberg, Jingjing Liang, Wei Zheng, Najaf Amin, Ulf de Faire, Bing Yu, Archie Campbell, Kari E. North, Salman M. Tajuddin, Fernando Pires Hartwig, Steve B. Kritchevsky, Tibor V. Varga, Pirjo Komulainen, Hugh Watkins, Johanna Kuusisto, Kurt Lohman, Rozenn N. Lemaitre, Ani Manichaikul, Dabeeru C. Rao, Kenneth Rice, Weihua Zhang, Franco Giulianini, Reedik Mägi, Solomon K. Musani, Wanqing Wen, Nicholas J. Wareham, Charles N. Rotimi, Marzyeh Amini, Rainer Rauramaa, Nicholette D. Palmer, Annette Peters, Neil R Poulter, Benjamin Lehne, Matthias Nauck, Harold Snieder, Donald W. Bowden, M. Arfan Ikram, Lisa de las Fuentes, C. Charles Gu, Xiaofeng Zhu, Markku Laakso, Tuomas O. Kilpeläinen, Ching-Ti Liu, Michael Boehnke, Jin-Fang Chai, Lili Milani, L. Adrienne Cupples, Yuri Milaneschi, Kiang Liu, Stephen Sidney, Alan B. Zonderman, Thomas W. Winkler, Ian J. Deary, Fumihiko Takeuchi, Mary K. Wojczynski, Pim van der Harst, Leo-Pekka Lyytikäinen, Jennifer G. Robinson, Chuan Gao, Xiao-Ou Shu, Diane M. Becker, Mohsen Ghanbari, Alanna C. Morrison, Jian-Min Yuan, Tomohiro Katsuya, Ivana Kolcic, Melanie Waldenberger, Terho Lehtimäki, Heikki A. Koistinen, Erin B. Ware, Ya Xing Wang, Marie Loh, Treva Rice, Qing Duan, Aldi T. Kraja, Sabanayagam Charumathi, Tien Yin Wong, Paul S. de Vries, Yujie Wang, Muhammad Riaz, Home Office, Action on Hearing Loss, Imperial College Healthcare NHS Trust- BRC Funding, British Heart Foundation, Medical Research Council (MRC), Wellcome Trust, National Institute for Health Research, Luan, Jian'an [0000-0003-3137-6337], Pietzner, Maik [0000-0003-3437-9963], Zhao, Jing Hua [0000-0003-4930-3582], Langenberg, Claudia [0000-0002-5017-7344], Wareham, Nicholas [0000-0003-1422-2993], Apollo - University of Cambridge Repository, APH - Mental Health, Psychiatry, APH - Digital Health, The University of Texas Health Science Center at Houston (UTHealth), National Institutes of Health [Bethesda] (NIH), Washington University in Saint Louis (WUSTL), University of Regensburg, Queen Mary University of London (QMUL), Washington University School of Medicine in St. Louis, Harbor UCLA Medical Center [Torrance, Ca.], University of North Carolina at Chapel Hill (UNC), Singapore National Eye Centre and Duke-NUS [Singapore], Singapore Eye Research Institute [Singapore] (SERI), National University of Singapore (NUS), Erasmus University Medical Center [Rotterdam] (Erasmus MC), Département de Biologie Computationnelle - Department of Computational Biology, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP), Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), University Management, Department of Medicine, University of Helsinki, Endokrinologian yksikkö, HUS Abdominal Center, Lifelines Cohort, Groningen, The Netherlands (Lifelines Cohort Study), Epidemiology, Neurology, Radiology & Nuclear Medicine, Internal Medicine, Life Course Epidemiology (LCE), Cardiovascular Centre (CVC), de Vries, Paul S, Brown, Michael R, Bentley, Amy R, Sung, Yun J, Winkler, Thomas W, Ntalla, Ioanna, Schwander, Karen, Kraja, Aldi T, Guo, Xiuqing, Franceschini, Nora, Cheng, Ching-Yu, Sim, Xueling, Vojinovic, Dina, Huffman, Jennifer E, Musani, Solomon K, Li, Changwei, Feitosa, Mary F, Richard, Melissa A, Noordam, Raymond, Aschard, Hugue, Bartz, Traci M, Bielak, Lawrence F, Deng, Xuan, Dorajoo, Rajkumar, Lohman, Kurt K, Manning, Alisa K, Rankinen, Tuomo, Smith, Albert V, Tajuddin, Salman M, Evangelou, Evangelo, Graff, Mariaelisa, Alver, Mari, Boissel, Mathilde, Chai, Jin Fang, Chen, Xu, Divers, Jasmin, Gandin, Ilaria, Gao, Chuan, Goel, Anuj, Hagemeijer, Yanick, Harris, Sarah E, Hartwig, Fernando P, He, Meian, Horimoto, Andrea R V R, Hsu, Fang-Chi, Jackson, Anne U, Kasturiratne, Anuradhani, Komulainen, Pirjo, Kühnel, Brigitte, Laguzzi, Federica, Lee, Joseph H, Luan, Jian'An, Lyytikäinen, Leo-Pekka, Matoba, Nana, Nolte, Ilja M, Pietzner, Maik, Riaz, Muhammad, Said, M Abdullah, Scott, Robert A, Sofer, Tamar, Stancáková, Alena, Takeuchi, Fumihiko, Tayo, Bamidele O, van der Most, Peter J, Varga, Tibor V, Wang, Yajuan, Ware, Erin B, Wen, Wanqing, Yanek, Lisa R, Zhang, Weihua, Zhao, Jing Hua, Afaq, Saima, Amin, Najaf, Amini, Marzyeh, Arking, Dan E, Aung, Tin, Ballantyne, Christie, Boerwinkle, Eric, Broeckel, Ulrich, Campbell, Archie, Canouil, Mickaël, Charumathi, Sabanayagam, Chen, Yii-Der Ida, Connell, John M, de Faire, Ulf, de Las Fuentes, Lisa, de Mutsert, Renée, de Silva, H Janaka, Ding, Jingzhong, Dominiczak, Anna F, Duan, Qing, Eaton, Charles B, Eppinga, Ruben N, Faul, Jessica D, Fisher, Virginia, Forrester, Terrence, Franco, Oscar H, Friedlander, Yechiel, Ghanbari, Mohsen, Giulianini, Franco, Grabe, Hans J, Grove, Megan L, Gu, C Charle, Harris, Tamara B, Heikkinen, Sami, Heng, Chew-Kiat, Hirata, Makoto, Hixson, James E, Howard, Barbara V, Ikram, M Arfan, Jacobs, David R, Johnson, Craig, Jonas, Jost Bruno, Kammerer, Candace M, Katsuya, Tomohiro, Khor, Chiea Chuen, Kilpeläinen, Tuomas O, Koh, Woon-Puay, Koistinen, Heikki A, Kolcic, Ivana, Kooperberg, Charle, Krieger, Jose E, Kritchevsky, Steve B, Kubo, Michiaki, Kuusisto, Johanna, Lakka, Timo A, Langefeld, Carl D, Langenberg, Claudia, Launer, Lenore J, Lehne, Benjamin, Lemaitre, Rozenn N, Li, Yize, Liang, Jingjing, Liu, Jianjun, Liu, Kiang, Loh, Marie, Louie, Tin, Mägi, Reedik, Manichaikul, Ani W, Mckenzie, Colin A, Meitinger, Thoma, Metspalu, Andre, Milaneschi, Yuri, Milani, Lili, Mohlke, Karen L, Mosley, Thomas H, Mukamal, Kenneth J, Nalls, Mike A, Nauck, Matthia, Nelson, Christopher P, Sotoodehnia, Nona, O'Connell, Jeff R, Palmer, Nicholette D, Pazoki, Raha, Pedersen, Nancy L, Peters, Annette, Peyser, Patricia A, Polasek, Ozren, Poulter, Neil, Raffel, Leslie J, Raitakari, Olli T, Reiner, Alex P, Rice, Treva K, Rich, Stephen S, Robino, Antonietta, Robinson, Jennifer G, Rose, Lynda M, Rudan, Igor, Schmidt, Carsten O, Schreiner, Pamela J, Scott, William R, Sever, Peter, Shi, Yuan, Sidney, Stephen, Sims, Mario, Smith, Blair H, Smith, Jennifer A, Snieder, Harold, Starr, John M, Strauch, Konstantin, Tan, Nichola, Taylor, Kent D, Teo, Yik Ying, Tham, Yih Chung, Uitterlinden, André G, van Heemst, Diana, Vuckovic, Dragana, Waldenberger, Melanie, Wang, Lihua, Wang, Yujie, Wang, Zhe, Wei, Wen Bin, Williams, Christine, Wilson, Gregory, Wojczynski, Mary K, Yao, Jie, Yu, Bing, Yu, Caizheng, Yuan, Jian-Min, Zhao, Wei, Zonderman, Alan B, Becker, Diane M, Boehnke, Michael, Bowden, Donald W, Chambers, John C, Deary, Ian J, Esko, Tõnu, Farrall, Martin, Franks, Paul W, Freedman, Barry I, Froguel, Philippe, Gasparini, Paolo, Gieger, Christian, Horta, Bernardo L, Kamatani, Yoichiro, Kato, Norihiro, Kooner, Jaspal S, Laakso, Markku, Leander, Karin, Lehtimäki, Terho, Magnusson, Patrik K E, Penninx, Brenda, Pereira, Alexandre C, Rauramaa, Rainer, Samani, Nilesh J, Scott, Jame, Shu, Xiao-Ou, van der Harst, Pim, Wagenknecht, Lynne E, Wang, Ya Xing, Wareham, Nicholas J, Watkins, Hugh, Weir, David R, Wickremasinghe, Ananda R, Zheng, Wei, Elliott, Paul, North, Kari E, Bouchard, Claude, Evans, Michele K, Gudnason, Vilmundur, Liu, Ching-Ti, Liu, Yongmei, Psaty, Bruce M, Ridker, Paul M, van Dam, Rob M, Kardia, Sharon L R, Zhu, Xiaofeng, Rotimi, Charles N, Mook-Kanamori, Dennis O, Fornage, Myriam, Kelly, Tanika N, Fox, Ervin R, Hayward, Caroline, van Duijn, Cornelia M, Tai, E Shyong, Wong, Tien Yin, Liu, Jingmin, Rotter, Jerome I, Gauderman, W Jame, Province, Michael A, Munroe, Patricia B, Rice, Kenneth, Chasman, Daniel I, Cupples, L Adrienne, Rao, Dabeeru C, Morrison, Alanna C, and Academic Medical Center

Subjects
Male, Epidemiology, Genome-wide association study, Cardiovascular, MESH: Genotype, Substance Misuse, Alcohol Use and Health, 0302 clinical medicine, Aetiology, triglycerides, 11 Medical and Health Sciences, Public, Environmental & Occupational Health, [STAT.AP]Statistics [stat]/Applications [stat.AP], MESH: Middle Aged, MESH: Life Style, genome wide, gene-alcohol interaction, lipid levels, Lipid Measurement, Lifelines Cohort, DENSITY-LIPOPROTEIN CHOLESTEROL, MESH: Young Adult, 030220 oncology & carcinogenesis, Kexin, LOW-FREQUENCY, MESH: Cholesterol, HDL, MESH: Cholesterol, LDL, MESH: Triglycerides, HDL, Alcohol Drinking, Genotype, alcohol consumption, MESH: Phenotype, LDL, lipids, 03 medical and health sciences, Genetics, Humans, Life Style, METAANALYSIS, 01 Mathematical Sciences, Aged, MESH: Adolescent, HDL CHOLESTEROL, MESH: Humans, Science & Technology, Cholesterol, APOBEC1, Lifelines Cohort, Groningen, The Netherlands (Lifelines Cohort Study), MESH: Vascular Endothelial Growth Factor B, Racial Groups, cholesterol, The Netherlands, MESH: Adult, CONSUMPTION, chemistry, MESH: Genome-Wide Association Study, [INFO.INFO-BI]Computer Science [cs]/Bioinformatics [q-bio.QM], Lipid profile, MESH: Female, MESH: Alcohol Drinking, MESH: Continental Population Groups, Vascular Endothelial Growth Factor B, Original Contributions, Blood lipids, VEGF-B, Medical and Health Sciences, Mathematical Sciences, BLOOD-LIPIDS, chemistry.chemical_compound, 2.1 Biological and endogenous factors, 030212 general & internal medicine, MESH: Aged, medicine.diagnostic_test, PLASMA, gene-environment interactions, Middle Aged, 3142 Public health care science, environmental and occupational health, Alcoholism, Phenotype, Female, gene-lifestyle interactions, genome-wide association studies, [STAT.ME]Statistics [stat]/Methodology [stat.ME], Life Sciences & Biomedicine, Groningen, Adult, Adolescent, Biology, Young Adult, medicine, CORONARY-HEART-DISEASE, Human Genome, Cholesterol, HDL, Lipid metabolism, Cholesterol, LDL, InterAct Consortium, MESH: Lipids, MESH: Male, INDIVIDUALS, [SDV.GEN.GH]Life Sciences [q-bio]/Genetics/Human genetics, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Genome-Wide Association Study
Abstract

© The Author(s) 2019. A person's lipid profile is influenced by genetic variants and alcohol consumption, but the contribution of interactions between these exposures has not been studied. We therefore incorporated gene-Alcohol interactions into a multiancestry genome-wide association study of levels of high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, and triglycerides. We included 45 studies in stage 1 (genome-wide discovery) and 66 studies in stage 2 (focused follow-up), for a total of 394,584 individuals from 5 ancestry groups. Analyses covered the period July 2014-November 2017. Genetic main effects and interaction effects were jointly assessed by means of a 2- degrees-of-freedom (df) test, and a 1-df test was used to assess the interaction effects alone. Variants at 495 loci were at least suggestively associated (P < 1 × 10?6) with lipid levels in stage 1 and were evaluated in stage 2, followed by combined analyses of stage 1 and stage 2. In the combined analysis of stages 1 and 2, a total of 147 independent loci were associated with lipid levels at P < 5 × 10?8 using 2-df tests, of which 18 were novel. No genome-wide-significant associations were found testing the interaction effect alone. The novel loci included several genes (proprotein convertase subtilisin/kexin type 5 (PCSK5), vascular endothelial growth factor B (VEGFB), and apolipoprotein B mRNA editing enzyme, catalytic polypeptide 1 (APOBEC1) complementation factor (A1CF)) that have a putative role in lipid metabolism on the basis of existing evidence from cellular and experimental models. National Heart, Lung, and Blood Institute; American Heart Association Grant

Published
2019

162. Coronary heart disease risk factor levels in eastern and western Finland from 1980 to 2011 in the cardiovascular risk in Young Finns study

Author

Leena Taittonen, Katja Pahkala, Nina Hutri-Kähönen, Costan G. Magnussen, Jorma Viikari, Lauri Vähämurto, Risto Telama, Markus Juonala, Terho Lehtimäki, Tapani Rönnemaa, Tomi Laitinen, Eero Jokinen, Mika Kähönen, Päivi Tossavainen, Olli T. Raitakari, Lastentautien yksikkö, Children's Hospital, Clinicum, University of Helsinki, and HUS Children and Adolescents

Subjects
Blood Glucose, Male, 0301 basic medicine, Blood Pressure, Coronary Disease, 030204 cardiovascular system & hematology, 0302 clinical medicine, Risk Factors, Medicine, Longitudinal cohort, Child, Finland, Atherosclerosis precursors, Metabolic Syndrome, education.field_of_study, Anthropometry, Geography, Incidence (epidemiology), Middle Aged, Cardiovascular disease, Adulthood, 16. Peace & justice, NORTH-KARELIA-PROJECT, Cholesterol, Cardiovascular Diseases, Child, Preschool, Hypertension, Population study, Female, MEDIA THICKNESS, Cardiology and Cardiovascular Medicine, Adult, Adolescent, MIGRATION, Population, Risk Assessment, SECULAR TRENDS, 03 medical and health sciences, Chd mortality, Humans, Risk factor, SHORT STATURE, education, Life Style, DECLINE, business.industry, MORTALITY, ta3121, INTIMA, Coronary heart disease, Fatty Liver, 030104 developmental biology, Social Class, 3121 General medicine, internal medicine and other clinical medicine, Longitudinal, FOLLOW-UP, business, Chd risk, Follow-Up Studies, Demography
Abstract

Background and aims In the 1960s and 1970s, Finland, mortality due to coronary heart disease (CHD) was over 30% higher among Finns residing in the east of the country compared with those residing in the west. Today, CHD mortality remains 20% higher among eastern Finns. The higher incidence of CHD mortality among eastern Finns has largely been explained by higher risk factor levels. Using a unique longitudinal cohort, we aimed to determine if participants who resided in eastern Finland during childhood had higher CHD risk factors in adulthood and from childhood to adulthood. Methods The study population included 2063 participants of the Cardiovascular Risk in Young Finns Study, born during the period 1962–1977, with risk factor data available from baseline (1980) when participants were aged 3–18 years, and had risk factor data collected again in adulthood (2011) when aged 34–49 years. Results Adult CHD risk factor profile was similar for those who resided in eastern or western Finland in childhood. Over life-course from 1980 to 2011, those subjects with childhood residency in eastern Finland had, on average, higher systolic (p = 0.006) and diastolic (p = 0.0009) blood pressures, total (p = 0.01) and LDL-cholesterol (p = 0.01), triglycerides (p = 0.04), apoB (p = 0.02), and serum glucose (p Conclusions Our sample of adult Finns aged 34–49 years had a similar CHD risk factor profile irrespective of whether they resided in eastern or western Finland during their childhood. However, when considering participants risk factor profiles over a 31-year period, those who resided in eastern Finland in childhood were associated with a less favorable CHD risk factor profile than those who resided in western Finland in childhood. The observed differences suggest that future CHD mortality might remain higher in eastern Finland compared with western Finland.

Published
2019

163. Dietary Intervention in Infancy and Cognitive Function in Young Adulthood: The Special Turku Coronary Risk Factor Intervention Project

Author

Suvi P. Rovio, Henri Salo, Harri Niinikoski, Hanna Lagström, Pia Salo, Jorma S.A. Viikari, Tapani Rönnemaa, Antti Jula, Olli T. Raitakari, and Katja Pahkala

Subjects
Adult, Young Adult, Cholesterol, Cognition, Risk Factors, Fatty Acids, Pediatrics, Perinatology and Child Health, Humans, Diet, Healthy, Child, Dietary Fats, Diet
Abstract

Consumption of saturated fatty acids (SAFAs), polyunsaturated fatty acids (PUFAs), cholesterol, and fiber have been linked with cognitive function in adults. We evaluated these associations from childhood by leveraging data from the Special Turku Coronary Risk Factor Intervention Project (STRIP).STRIP recruited children aged 5 months and randomly assigned them into intervention/control groups. The intervention introduced a heart-healthy diet, characterized mainly by low consumption of SAFAs and cholesterol, through counseling at least biannually between age 7 months and 20 years. Diet was assessed repeatedly using food diaries. Six years after the end of the intervention phase, at age 26 years, the participants were invited to the first postintervention follow-up, which included cognitive testing that covered learning and memory, verbal memory, short-term working memory, reaction time, information processing, and cognitive flexibility and inhibitory control. We studied the associations of the STRIP intervention and the consumptions of SAFAs, PUFAs, cholesterol, and fiber within these cognitive domains.Participants in the STRIP intervention group had better cognitive flexibility and inhibitory control and were better able to manage conflicting information and ignore task-irrelevant information (0.18 SD higher in the intervention group, adjusted for sex and socioeconomic status). No associations were observed with the dietary components studied.The infancy-onset STRIP intervention, which promoted a heart-healthy diet, was favorably associated with cognitive flexibility and inhibitory control at age 26 years. No associations were found for the intervention targets studied, indicating that these specific dietary components did not underlie the observed effect of the intervention.

Published
2022

164. Abstract 067: Does BP Trajectory Across Childhood Predict Adult HTN? The International Childhood CV Cohorts Consortium

Author

Trudy L. Burns, Alan R. Sinaiko, Ronald J. Prineas, Alison Venn, Lydia A. Bazzano, David R. Jacobs, Markus Juonala, Julia Steinberger, Terence Dwyer, Olli T. Raitakari, Philip R. Khoury, Jessica G. Woo, and Elaine M. Urbina

Subjects
medicine.medical_specialty, Pediatrics, Blood pressure, business.industry, Physiology (medical), Epidemiology, Trajectory, medicine, Cardiology and Cardiovascular Medicine, business, Pediatric cardiology
Abstract

The relationship between single measures of systolic blood pressure (SBP) in youth and adult levels is weak. We sought to define trajectories of SBP over childhood to determine ability to predict adult hypertension (HTN). In the International Childhood CV Cohort (i3C) Consortium, we constructed SBP trajectories in 11,482 participants (mean age 8.0 + 2.0 years at time of first measure, 47% male, 25% non-Caucasian) who had at least 3 SBPs in youth between the ages of 4 and

Published
2021

165. Variants associated with HHIP expression have sex-differential effects on lung function

Author

Carl A. Melbourne, Caroline Hayward, Stefan Karrasch, Dirk Keidel, Katherine A. Fawcett, Susan M. Ring, Yohan Bossé, Carol A. Wang, Ben Michael Brumpton, Claudia Langenberg, Peter K. Joshi, Ke Hao, Igor Rudan, David J. Porteous, Don D. Sin, Raquel Granell, Blair H. Smith, Jian'an Luan, Kristian Hveem, Sarah E. Harris, Sandosh Padmanabhan, Archie Campbell, Sebastian May-Wilson, Veronique Vitart, Nicola Pirastu, Arnulf Langhammer, Craig E. Pennell, John M. Starr, Stefan Weiss, Karina Patasova, Nicholas J. Wareham, James F. Wilson, Deborah Jarvis, Tim D. Spector, Nick Shrine, David P. Strachan, Martin D. Tobin, Beate Stubbe, David M. Evans, Kirsi H. Pietiläinen, Mangino Massimo, Ian P. Hall, Graham L. Hall, Jaakko Kaprio, Ralf Ewert, Rachel E. Foong, Claudia Flexeder, Louise V. Wain, Ma'en Obeidat, Cristen J. Willer, Leo-Pekka Lyytikäinen, Olli T. Raitakari, John Henderson, Konstantin Strauch, Marta R Moksnes, Cosetta Minelli, Nicole Probst-Hensch, Pirro G. Hysi, Anna L. Guyatt, Henry Völzke, Thomas Meitinger, Peter D. Sly, Ozren Polasek, Anne Richmond, Mika Kähönen, Maarten van den Berge, Medea Imboden, Thibaud Boutin, Lucija Klaric, Laura Portas, Terho Lehtimäki, Ian J. Deary, Taina Rantanen, Catherine John, Teemu Palviainen, Fawcett, Katherine A [0000-0002-6675-2112], Obeidat, Ma'en [0000-0002-5443-2752], Shrine, Nick [0000-0003-3641-4371], Weiss, Stefan [0000-0002-3553-4315], May-Wilson, Sebastian [0000-0003-2668-5717], Boutin, Thibaud S [0000-0003-4754-1675], Portas, Laura [0000-0003-1789-1893], Harris, Sarah E [0000-0002-4941-5106], Lyytikäinen, Leo-Pekka [0000-0002-7200-5455], Palviainen, Teemu [0000-0002-7847-8384], Keidel, Dirk [0000-0003-4706-5728], Minelli, Cosetta [0000-0001-9166-3958], Langenberg, Claudia [0000-0002-5017-7344], Bossé, Yohan [0000-0002-3067-3711], Van den Berge, Maarten [0000-0002-9336-7340], Sin, Don D [0000-0002-0756-6643], Campbell, Archie [0000-0003-0198-5078], Porteous, David [0000-0003-1249-6106], Padmanabhan, Sandosh [0000-0003-3869-5808], Smith, Blair H [0000-0002-5362-9430], Ring, Sue [0000-0003-3103-9330], Rantanen, Taina [0000-0002-1604-1945], Pennell, Craig E [0000-0002-0937-6165], Kaprio, Jaakko [0000-0002-3716-2455], Vitart, Veronique [0000-0002-4991-3797], Hayward, Caroline [0000-0002-9405-9550], Hall, Ian P [0000-0001-9933-3216], Wain, Louise V [0000-0003-4951-1867], Apollo - University of Cambridge Repository, Groningen Research Institute for Asthma and COPD (GRIAC), Technology Centre, University of Helsinki, Institute for Molecular Medicine Finland, Genetic Epidemiology, HUS Abdominal Center, Department of Medicine, Clinicum, CAMM - Research Program for Clinical and Molecular Metabolism, Department of Public Health, Research Programs Unit, Tampere University, Clinical Medicine, Department of Clinical Chemistry, TAYS Heart Centre, and Department of Clinical Physiology and Nuclear Medicine

Subjects
0301 basic medicine, Spirometry, medicine.medical_specialty, HHIP, Medicine (miscellaneous), Expression, Genome-wide Interaction Study, Hhip, Lung Function, Sex, Single-nucleotide polymorphism, Biology, 3121 Internal medicine, General Biochemistry, Genetics and Molecular Biology, 03 medical and health sciences, 0302 clinical medicine, Genome-wide interaction study, Lung function, Internal medicine, expression, medicine, sex, Allele, Enhancer, Gene, Lung, genome-wide interaction study, medicine.diagnostic_test, 1184 Genetics, developmental biology, physiology, lung function, ALSPAC, Differential effects, 030104 developmental biology, Endocrinology, medicine.anatomical_structure, 030228 respiratory system, 3121 General medicine, internal medicine and other clinical medicine, 3111 Biomedicine
Abstract

Background: Lung function is highly heritable and differs between the sexes throughout life. However, little is known about sex-differential genetic effects on lung function. We aimed to conduct the first genome-wide genotype-by-sex interaction study on lung function to identify genetic effects that differ between males and females. Methods: We tested for interactions between 7,745,864 variants and sex on spirometry-based measures of lung function in UK Biobank (N=303,612), and sought replication in 75,696 independent individuals from the SpiroMeta consortium. Results: Five independent single-nucleotide polymorphisms (SNPs) showed genome-wide significant (P-8) interactions with sex on lung function, and 21 showed suggestive interactions (P-6). The strongest signal, from rs7697189 (chr4:145436894) on forced expiratory volume in 1 second (FEV1) (P=3.15x10-15), was replicated (P=0.016) in SpiroMeta. The C allele increased FEV1 more in males (untransformed FEV1 β=0.028 [SE 0.0022] litres) than females (β=0.009 [SE 0.0014] litres), and this effect was not accounted for by differential effects on height, smoking or pubertal age. rs7697189 resides upstream of the hedgehog-interacting protein (HHIP) gene and was previously associated with lung function and HHIP lung expression. We found HHIP expression was significantly different between the sexes (P=6.90x10-6), but we could not detect sex differential effects of rs7697189 on expression. Conclusions: We identified a novel genotype-by-sex interaction at a putative enhancer region upstream of the HHIP gene. Establishing the mechanism by which HHIP SNPs have different effects on lung function in males and females will be important for our understanding of lung health and diseases in both sexes.

Published
2021

166. Cardiovascular Risk Factor Trajectories Since Childhood and Cognitive Performance in Midlife The Cardiovascular Risk in Young Finns Study

Author

Leena Taittonen, Eero Jokinen, Mika Kähönen, Juuso O. Hakala, Markus Juonala, Katja Pahkala, Suvi P. Rovio, Jorma Viikari, Olli T. Raitakari, Nina Hutri-Kähönen, Päivi Tossavainen, Terho Lehtimäki, Tomi Laitinen, Pia Salo, HUS Children and Adolescents, Lastentautien yksikkö, Children's Hospital, and Clinicum

Subjects
Gerontology, Adult, Male, cardiovascular risk, Adolescent, Cardiovascular risk factors, Blood lipids, population-based studies, ADULTHOOD, 030204 cardiovascular system & hematology, Neuropsychological Tests, SUBCLINICAL ATHEROSCLEROSIS, PROFILE, community health planning, 03 medical and health sciences, 0302 clinical medicine, Cognition, Risk Factors, 3123 Gynaecology and paediatrics, Physiology (medical), Medicine, Humans, longitudinal studies, Effects of sleep deprivation on cognitive performance, Risk factor, Child, cognitive function, 2. Zero hunger, DECLINE, business.industry, CHOLESTEROL, DEMENTIA, ASSOCIATION, CANTAB, Middle Aged, Harm, Blood pressure, Cardiovascular Diseases, Child, Preschool, 3121 General medicine, internal medicine and other clinical medicine, Female, VASCULAR RISK, HEALTH, Cardiology and Cardiovascular Medicine, business, 030217 neurology & neurosurgery, Elevated body mass index
Abstract

Background: Cardiovascular risk factors, such as high blood pressure, adverse serum lipids, and elevated body mass index in midlife, may harm cognitive performance. It is important to note that longitudinal accumulation of cardiovascular risk factors since childhood may be associated with cognitive performance already since childhood, but the previous evidence is scarce. We studied the associations of cardiovascular risk factors from childhood to midlife, their accumulation, and midlife cognitive performance. Methods: From 1980, a population-based cohort of 3596 children (3–18 years of age) have been repeatedly followed up for 31 years. Blood pressure, serum lipids, and body mass index were assessed in all follow-ups. Cardiovascular risk factor trajectories from childhood to midlife were identified using latent class growth mixture modeling. Cognitive testing was performed in 2026 participants 34 to 49 years of age using a computerized test. The associations of the cardiovascular risk factor trajectories and cognitive performance were studied for individual cardiovascular risk factors and cardiovascular risk factor accumulation. Results: Consistently high systolic blood pressure (β=–0.262 SD [95% CI, –0.520 to –0.005]) and serum total cholesterol (β=–0.214 SD [95% CI, –0.365 to –0.064]) were associated with worse midlife episodic memory and associative learning compared with consistently low values. Obesity since childhood was associated with worse visual processing and sustained attention (β=–0.407 SD [95% CI, –0.708 to –0.105]) compared with normal weight. An inverse association was observed for the cardiovascular risk factor accumulation with episodic memory and associative learning ( P for trend=0.008; 3 cardiovascular risk factors: β=–0.390 SD [95% CI, –0.691 to –0.088]), with visual processing and sustained attention ( P for trendP for trend=0.048; 2 cardiovascular risk factors: β=–0.164 SD [95% CI, –0.318 to –0.010]). Conclusions: Longitudinal elevated systolic blood pressure, high serum total cholesterol, and obesity from childhood to midlife were inversely associated with midlife cognitive performance. It is important to note that the higher the number of cardiovascular risk factors, the worse was the observed cognitive performance. Therefore, launching preventive strategies against cardiovascular risk factors beginning from childhood might benefit primordial promotion of cognitive health in adulthood.

Published
2021

167. Longitudinal profiling of metabolic ageing trends in two population cohorts of young adults

Author

Ville-Petteri Mäkinen, Mari Karsikas, Johannes Kettunen, Terho Lehtimäki, Mika Kähönen, Jorma Viikari, Markus Perola, Veikko Salomaa, Marjo-Riitta Järvelin, Olli T Raitakari, and Mika Ala-Korpela

Subjects
Epidemiology, General Medicine
Abstract

Background Quantification of metabolic changes over the human life course is essential to understanding ageing processes. Yet longitudinal metabolomics data are rare and long gaps between visits can introduce biases that mask true trends. We introduce new ways to process quantitative time-series population data and elucidate metabolic ageing trends in two large cohorts. Methods Eligible participants included 1672 individuals from the Cardiovascular Risk in Young Finns Study and 3117 from the Northern Finland Birth Cohort 1966. Up to three time points (ages 24–49 years) were analysed by nuclear magnetic resonance metabolomics and clinical biochemistry (236 measures). Temporal trends were quantified as median change per decade. Sample quality was verified by consistency of shared biomarkers between metabolomics and clinical assays. Batch effects between visits were mitigated by a new algorithm introduced in this report. The results below satisfy multiple testing threshold of P Results Women gained more weight than men (+6.5% vs +5.0%) but showed milder metabolic changes overall. Temporal sex differences were observed for C-reactive protein (women +5.1%, men +21.1%), glycine (women +5.2%, men +1.9%) and phenylalanine (women +0.6%, men +3.5%). In 566 individuals with ≥+3% weight gain vs 561 with weight change ≤−3%, divergent patterns were observed for insulin (+24% vs −10%), very-low-density-lipoprotein triglycerides (+32% vs −6%), high-density-lipoprotein2 cholesterol (−6.5% vs +4.7%), isoleucine (+5.7% vs −6.0%) and C-reactive protein (+25% vs −22%). Conclusion We report absolute and proportional trends for 236 metabolic measures as new reference material for overall age-associated and specific weight-driven changes in real-world populations.

Published
2021

168. Publisher Correction: A meta-analysis of genome-wide association studies identifies multiple longevity genes

Author

Sarah Cubaynes, Joanne M. Murabito, Eric S. Orwoll, Iris E. Jansen, Joanna Collerton, Vilmundur Gudnason, Mikko Hurme, Paola Sebastiani, Carol Jagger, Carmen Martin-Ruiz, Douglas P. Kiel, Henne Holstege, Kenny Ye, Pilar Galan, Wolfgang Lieb, Diana van Heemst, Janina Dose, Wanlin Zheng, Ilkka Seppälä, Ashley van der Spek, Jessica D. Faul, Nir Barzilai, David R. Weir, James W. Vaupel, Wiesje M. van der Flier, Dan E. Arking, Terho Lehtimäki, Marja Jylhä, Thomas B. L. Kirkwood, Andrew Kingston, Marcel J. T. Reinders, Jean-François Deleuze, Cornelia M. van Duijn, Hélène Blanché, Anne B. Newman, Chao Nie, Elizabeth J. Becker, Daniel S. Evans, P. Eline Slagboom, Marianne Nygaard, Lene Christiansen, Jean Marie Robine, Junxia Min, Almut Nebel, Tamara B. Harris, Lenore J. Launer, Mary K. Wojczynski, Ellen A. Nohr, Alice M. Arnold, Olli T. Raitakari, Birgit Debrabant, Jerome I. Rotter, Thorkild I. A. Sørensen, André G. Uitterlinden, Steven R. Cummings, Kristin L. Ayers, Jennifer A. Smith, Joris Deelen, Yi Zeng, Chloé Sarnowski, Heather J. Cordell, Karen Davies, Kent D. Taylor, Mika Kähönen, Albert V. Smith, Najaf Amin, Rachel Duncan, Michael A. Province, Leo-Pekka Lyytikäinen, Kathryn L. Lunetta, Kaare Christensen, Sharon L.R. Kardia, Thomas T. Perls, Erin B. Ware, Martijn Huisman, Mary L. Biggs, Marian Beekman, Sven J. van der Lee, David Karasik, Niccolò Tesi, Xiaomin Liu, Gil Atzmon, Claudio Franceschi, and Bruce M. Psaty

Subjects
Apolipoprotein E2, Science, Apolipoprotein E4, Longevity, MEDLINE, General Physics and Astronomy, Genome-wide association study, Diseases, Computational biology, Biology, Longevity genes, Genome-wide association studies, GeneralLiterature_MISCELLANEOUS, General Biochemistry, Genetics and Molecular Biology, SNP, Humans, Endoplasmic Reticulum Chaperone BiP, Heat-Shock Proteins, Multidisciplinary, Published Erratum, General Chemistry, Publisher Correction, Ageing, ComputingMethodologies_PATTERNRECOGNITION, Risk factors, Meta-analysis, ComputingMethodologies_DOCUMENTANDTEXTPROCESSING, Genome-Wide Association Study
Abstract

Human longevity is heritable, but genome-wide association (GWA) studies have had limited success. Here, we perform two meta-analyses of GWA studies of a rigorous longevity phenotype definition including 11,262/3484 cases surviving at or beyond the age corresponding to the 90th/99th survival percentile, respectively, and 25,483 controls whose age at death or at last contact was at or below the age corresponding to the 60th survival percentile. Consistent with previous reports, rs429358 (apolipoprotein E (ApoE) ε4) is associated with lower odds of surviving to the 90th and 99th percentile age, while rs7412 (ApoE ε2) shows the opposite. Moreover, rs7676745, located near GPR78, associates with lower odds of surviving to the 90th percentile age. Gene-level association analysis reveals a role for tissue-specific expression of multiple genes in longevity. Finally, genetic correlation of the longevity GWA results with that of several disease-related phenotypes points to a shared genetic architecture between health and longevity.

Published
2021

169. Metabolic profiling of angiopoietin-like protein 3 and 4 inhibition : a drug-target Mendelian randomization analysis

Author

Veikko Salomaa, Mika Kähönen, Michael V. Holmes, Clare Oliver-Williams, Johannes Kettunen, Jorma S. A. Viikari, Markus Perola, Qin Wang, Adam S. Butterworth, Marjo-Riitta Järvelin, Mika Ala-Korpela, John Danesh, Terho Lehtimäki, Olli T. Raitakari, Institute for Molecular Medicine Finland, University of Helsinki, Danesh, John [0000-0003-1158-6791], Butterworth, Adam [0000-0002-6915-9015], Apollo - University of Cambridge Repository, UNIVERSITY OF OULU, Tampere University, Clinical Medicine, Department of Clinical Chemistry, and Department of Clinical Physiology and Nuclear Medicine

Subjects
medicine.medical_specialty, Drug targets, Type 2 diabetes, 030204 cardiovascular system & hematology, 3121 Internal medicine, Lipoprotein particle, 03 medical and health sciences, Lipoprotein subclasses, 0302 clinical medicine, ANGPTL4, ANGPTL3, Internal medicine, Genotype, Mendelian randomization, Glycoprotein acetyls, medicine, Angiopoietin-Like Protein 4, Humans, AcademicSubjects/MED00200, 030212 general & internal medicine, 1102 Cardiorespiratory Medicine and Haematology, Angiopoietin-Like Protein 3, Lipoprotein lipase, business.industry, Clnical Research, Epidemiology and Prevention, 1103 Clinical Sciences, Lipoprotein lipids, Mendelian Randomization Analysis, medicine.disease, Editor's Choice, Endocrinology, Angiopoietin-like Proteins, Cardiovascular System & Hematology, Diabetes Mellitus, Type 2, Pharmaceutical Preparations, 3121 General medicine, internal medicine and other clinical medicine, Amino acids, lipids (amino acids, peptides, and proteins), 3111 Biomedicine, LPL, Cardiology and Cardiovascular Medicine, business, Angiopoietins, Lipoprotein
Abstract

Aims Angiopoietin-like protein 3 (ANGPTL3) and 4 (ANGPTL4) inhibit lipoprotein lipase (LPL) and represent emerging drug targets to lower circulating triglycerides and reduce cardiovascular risk. To investigate the molecular effects of genetic mimicry of ANGPTL3 and ANGPTL4 inhibition and compare them to the effects of genetic mimicry of LPL enhancement. Methods and results Associations of genetic variants in ANGPTL3 (rs11207977-T), ANGPTL4 (rs116843064-A), and LPL (rs115849089-A) with an extensive serum lipid and metabolite profile (208 measures) were characterized in six cohorts of up to 61 240 participants. Genetic associations with anthropometric measures, glucose-insulin metabolism, blood pressure, markers of kidney function, and cardiometabolic endpoints via genome-wide summary data were also explored. ANGPTL4 rs116843064-A and LPL rs115849089-A displayed a strikingly similar pattern of associations across the lipoprotein and lipid measures. However, the corresponding associations with ANGPTL3 rs11207977-T differed, including those for low-density lipoprotein and high-density lipoprotein particle concentrations and compositions. All three genotypes associated with lower concentrations of an inflammatory biomarker glycoprotein acetyls and genetic mimicry of ANGPTL3 inhibition and LPL enhancement were also associated with lower C-reactive protein. Genetic mimicry of ANGPTL4 inhibition and LPL enhancement were associated with a lower waist-to-hip ratio, improved insulin-glucose metabolism, and lower risk of coronary heart disease and type 2 diabetes, whilst genetic mimicry of ANGPTL3 was associated with improved kidney function. Conclusions Genetic mimicry of ANGPTL4 inhibition and LPL enhancement have very similar systemic metabolic effects, whereas genetic mimicry of ANGPTL3 inhibition showed differing metabolic effects, suggesting potential involvement of pathways independent of LPL. Genetic mimicry of ANGPTL4 inhibition and LPL enhancement were associated with a lower risk of coronary heart disease and type 2 diabetes. These findings reinforce evidence that enhancing LPL activity (either directly or via upstream effects) through pharmacological approaches is likely to yield benefits to human health., Graphical Abstract

Published
2021

170. IDO activity forecasts obesity in males and premenopausal females in a 10-year follow-up study:The Cardiovascular Risk in Young Finns Study

Author

Jorma Viikari, Mikko Hurme, Costan G. Magnussen, Mika Kähönen, Risto Kaaja, Petri Niinisalo, Terho Lehtimäki, Markus Juonala, Olli T. Raitakari, Tampere University, Department of Clinical Physiology and Nuclear Medicine, Clinical Medicine, BioMediTech, and Department of Clinical Chemistry

Subjects
Adult, Male, medicine.medical_specialty, Longitudinal study, Waist, 3121 Internal medicine, Gastroenterology, Body Mass Index, Young Adult, Risk Factors, Diabetes mellitus, Internal medicine, medicine, Humans, Indoleamine-Pyrrole 2,3,-Dioxygenase, Obesity, Risk factor, Finland, Triglycerides, business.industry, Hypertriglyceridemia, medicine.disease, Cardiovascular Diseases, Heart Disease Risk Factors, Relative risk, Female, 3111 Biomedicine, Cardiology and Cardiovascular Medicine, business, Body mass index, Follow-Up Studies
Abstract

Background and aims: Indoleamine 2,3-dioxygenase (IDO) is an intracellular enzyme associated with artery wall inflammation. Previous studies have verified correlation between IDO activity and early signs of atherosclerosis especially in females. We aimed to elucidate the relationship between an estimate of IDO activity and atherosclerotic risk factors related to non-alchohol-fatty liver (NAFLD) in a 6- and 10-year follow-up. Methods: Estimates of IDO activity along with complete risk factor data were measured from females (n = 506; age 24–39) and males (n = 421; age 24–39) in 2001. Risk factor measurements were conducted again in 2007 and 2011. Statistical examinations were carried out by Pearson correlation and risk ratio analysis. Results: In females, age-adjusted IDO correlated with body mass index (BMI) (p = 0.0008), waist (p = 0.0009), C-reactive protein (CRP) (p = 0.0014) and logarithmically modified triglycerides (p = 0.0488) in 2007. Correlation remained significant with BMI (p = 0.0007) and waist (p = 0.0063) in 2011. In males, age-adjusted IDO correlated with waist (p = 0.0367) and high-density lipoprotein cholesterol (HDL-C) (p = 0.0489) in 2007. Correlation remained significant with HDL-C (p = 0.0348) in 2011. In risk ratio analysis, relationship between IDO and obesity was confirmed in females after 10 years (RR = 1.026, p = 0.0147, 95% CI) and in males after 6 and 10 years (RR = 1.019, p = 0.0091, 95% CI and RR = 1.015, p = 0.0404, 95% CI, respectively) when the data was adjusted for age and BMI. Conclusions: IDO activity correlated with obesity and factors related to NAFLD, namely obesity of visceral type, hypertriglyceridemia and CRP (in females), well-characterized risk factors for diabetes and atherosclerosis in 6- and 10-year follow-up in males and premenopausal females. publishedVersion

Published
2021

172. Achievement of the Targets of the 20-Year Infancy-Onset Dietary Intervention—Association with Metabolic Profile from Childhood to Adulthood

Author

Suvi P. Rovio, Laurie A. Matthews, Harri Niinikoski, Katja Pahkala, Tomi T. Laitinen, Miia Lehtovirta, Mika Ala-Korpela, Olli T. Raitakari, Antti Jula, Joel Nuotio, Tapani Rönnemaa, Jorma Viikari, and Hanna Lagström

Subjects
Dietary Fiber, Male, Saturated fat, Coronary Disease, 030204 cardiovascular system & hematology, Nutrition Policy, Cholesterol, Dietary, Fatty Acids, Monounsaturated, Fiber intake, Eating, 0302 clinical medicine, Vegetables, 030212 general & internal medicine, Prospective Studies, Total energy, Child, Dietary fat, Finland, 2. Zero hunger, chemistry.chemical_classification, Whole Grains, Nutrition and Dietetics, Fatty Acids, food and beverages, Lipids, metabolomics, Diet Records, 3. Good health, Child, Preschool, Fatty Acids, Unsaturated, lipids (amino acids, peptides, and proteins), Female, Sucrose intake, Guideline Adherence, Diet, Healthy, lcsh:Nutrition. Foods and food supply, Metabolic profile, Polyunsaturated fatty acid, medicine.medical_specialty, Adolescent, lcsh:TX341-641, primordial prevention, Article, 03 medical and health sciences, Young Adult, Internal medicine, medicine, Humans, business.industry, metabolic profiling, Infant, Cholesterol, LDL, Feeding Behavior, Dietary Fats, Endocrinology, chemistry, Heart Disease Risk Factors, Fruit, quality of diet, business, Energy Intake, diet, Biomarkers, Food Science, Lipoprotein
Abstract

The Special Turku Coronary Risk Factor Intervention Project (STRIP) is a prospective infancy-onset randomized dietary intervention trial targeting dietary fat quality and cholesterol intake, and favoring consumption of vegetables, fruit, and whole-grains. Diet (food records) and circulating metabolites were studied at six time points between the ages of 9–19 years (n = 549–338). Dietary targets for this study were defined as (1) the ratio of saturated fat (SAFA) to monounsaturated and polyunsaturated fatty acids (MUFA + PUFA) &lt, 1:2, (2) intake of SAFA &lt, 10% of total energy intake, (3) fiber intake ≥ 80th age-specific percentile, and (4) sucrose intake ≤ 20th age-specific percentile. Metabolic biomarkers were quantified by high-throughput nuclear magnetic resonance metabolomics. Better adherence to the dietary targets, regardless of study group allocation, was assoiated with higher serum proportion of PUFAs, lower serum proportion of SAFAs, and a higher degree of unsaturation of fatty acids. Achieving ≥ 1 dietary target resulted in higher low-density lipoprotein (LDL) particle size, lower circulating LDL subclass lipid concentrations, and lower circulating lipid concentrations in medium and small high-density lipoprotein subclasses compared to meeting 0 targets. Attaining more dietary targets (≥2) was associated with a tendency to lower lipid concentrations of intermediate-density lipoprotein and very low-density lipoprotein subclasses. Thus, adherence to dietary targets is favorably associated with multiple circulating fatty acids and lipoprotein subclass lipid concentrations, indicative of better cardio-metabolic health.

Published
2021
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173. Gene regulation contributes to explain the impact of early life socioeconomic disadvantage on adult inflammatory levels in two cohort studies

Author

Olli T. Raitakari, Menno Pruijm, Michelle Kelly-Irving, Belen Ponte, Nicolas Vuilleumier, Eleonora Porcu, Silvia Stringhini, Olivier Delaneau, Marc Chadeau-Hyam, Pashupati P. Mishra, Murielle Bochud, Zoltán Kutalik, Terho Lehtimäki, Cristian Carmeli, Mika Kivimäki, Emmanouil T. Dermitzakis, Georg Ehret, Cyrille Delpierre, Mika Kähönen, Nasser A. Dhayat, Paolo Vineis, Tampere University, Department of Clinical Chemistry, Clinical Medicine, Department of Clinical Physiology and Nuclear Medicine, and Commission of the European Communities

Subjects
Male, 0301 basic medicine, Molecular biology, Bioinformatics, Epigenesis, Genetic, Transcriptome, 0302 clinical medicine, ddc:576.5, Longitudinal Studies, 030212 general & internal medicine, 610 Medicine & health, Child, Finland, Aged, 80 and over, ddc:616, Socioeconomic disadvantage, Regulation of gene expression, 0303 health sciences, Multidisciplinary, Middle Aged, C-Reactive Protein, DNA methylation, Medicine, Female, medicine.symptom, Switzerland, Cohort study, Adult, Science, Inflammation, Biology, Vulnerable Populations, Article, Life Change Events, 03 medical and health sciences, medicine, Humans, Epigenetics, Gene, Aged, ddc:613, 030304 developmental biology, Models, Statistical, Gene Expression Profiling, DNA Methylation, 3126 Surgery, anesthesiology, intensive care, radiology, Computational biology and bioinformatics, Disadvantaged, 030104 developmental biology, Risk factors, Socioeconomic Factors, Immune System, Biomarkers
Abstract

Individuals experiencing socioeconomic disadvantage in childhood have a higher rate of inflammation-related diseases decades later. Little is known about the mechanisms linking early life experiences to the functioning of the immune system in adulthood. To address this, we explore the relationship across social-to-biological layers of early life social exposures on levels of adulthood inflammation and the mediating role of gene regulatory mechanisms, epigenetic and transcriptomic profiling from blood, in 2,329 individuals from two European cohort studies. Consistently across both studies, we find transcriptional activity explains a substantive proportion (78% and 26%) of the estimated effect of early life disadvantaged social exposures on levels of adulthood inflammation. Furthermore, we show that mechanisms other than cis DNA methylation may regulate those transcriptional fingerprints. These results further our understanding of social-to-biological transitions by pinpointing the role of gene regulation that cannot fully be explained by differential cis DNA methylation.

Published
2021

174. Association of lifetime blood pressure with adulthood exercise blood pressure response : the cardiovascular risk in young Finns study

Author

Nina Hutri-Kähönen, Markus Juonala, Emilia Kähönen, Mika Kähönen, Terho Lehtimäki, Atte Haarala, Olli T. Raitakari, Kristiina Pälve, Heikki Aatola, Janne Hulkkonen, Kalle Sipilä, Tampere University, Department of Clinical Physiology and Nuclear Medicine, Clinical Medicine, TAYS Heart Centre, Department of Clinical Chemistry, and Department of Paediatrics

Subjects
Male, medicine.medical_specialty, Adolescent, Blood Pressure, 030204 cardiovascular system & hematology, 3121 Internal medicine, Elevated blood, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, Internal Medicine, medicine, Humans, Longitudinal Studies, 030212 general & internal medicine, Child, Exercise, Finland, business.industry, General Medicine, 3142 Public health care science, environmental and occupational health, 3. Good health, Blood pressure, Child, Preschool, Hypertension, Exercise Test, Cardiology, Female, sense organs, 3111 Biomedicine, Cardiology and Cardiovascular Medicine, business
Abstract

Purpose: Elevated blood pressure (BP) in childhood has been associated with increased adulthood BP. However, BP and its change from childhood to adulthood and the risk of exaggerated adulthood exercise BP response are largely unknown. Therefore, we studied the association of childhood and adulthood BP with adulthood exercise BP response. Materials and methods: This investigation consisted of 406 individuals participating in the ongoing Cardiovascular Risk in Young Finns Study (baseline in 1980, at age of 6–18 years; follow-up in adulthood in 27–29 years since baseline). In childhood BP was classified as elevated according to the tables from the International Child Blood Pressure References Establishment Consortium, while in adulthood BP was considered elevated if systolic BP was ≥120 mmHg or diastolic BP was ≥80 mmHg or if use of antihypertensive medications was self-reported. A maximal cardiopulmonary exercise test with BP measurements was performed by participants in 2008–2009, and exercise BP was considered exaggerated (EEBP) if peak systolic blood pressure exceeded 210 mmHg in men and 190 mmHg in women. Results: Participants with consistently high BP from childhood to adulthood and individuals with normal childhood but high adulthood BP had an increased risk of EEBP response in adulthood (relative risk [95% confidence interval], 3.32 [2.05–5.40] and 3.03 [1.77–5.17], respectively) in comparison with individuals with normal BP both in childhood and adulthood. Interestingly, individuals with elevated BP in childhood but not in adulthood also had an increased risk of EEBP [relative risk [95% confidence interval], 2.17 [1.35–3.50]). Conclusions: These findings reinforce the importance of achieving and sustaining normal blood pressure from childhood through adulthood. publishedVersion

Published
2021

175. Physical inactivity from youth to adulthood and adult cardiometabolic risk profile

Author

Britt Marie Loo, Eero Jokinen, Harri Helajärvi, Costan G. Magnussen, Nina Hutri-Kähönen, Suvi P. Rovio, Katja Pahkala, Olli J. Heinonen, Tuija Tammelin, Jorma Viikari, Päivi Tossavainen, Mirja Hirvensalo, Kristiina Pälve, Markus Juonala, Petri Kallio, Tomi Laitinen, and Olli T. Raitakari

Subjects
Adult, medicine.medical_specialty, elintavat, Waist, Adolescent, longitudinal, Epidemiology, medicine.medical_treatment, inactive lifestyle, pitkittäistutkimus, Lower risk, 01 natural sciences, Body Mass Index, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Risk Factors, Internal medicine, medicine, Humans, 030212 general & internal medicine, 0101 mathematics, Child, Exercise, Finland, 2. Zero hunger, Triglyceride, business.industry, Insulin, cardiovascular, 010102 general mathematics, Public Health, Environmental and Occupational Health, lapsuus, medicine.disease, childhood [CVD], Obesity, Blood pressure, chemistry, Cardiovascular Diseases, Child, Preschool, sydän- ja verisuonitaudit, nuoruus, Metabolic syndrome, Sedentary Behavior, Waist Circumference, business, Body mass index, terveysriskit, fyysinen aktiivisuus
Abstract

Adults with a low physical activity (PA) level are at increased risk for cardiometabolic diseases, but little is known on the association between physical inactivity since youth and cardiometabolic health in adulthood. We investigated the association of persistent physical inactivity from youth to adulthood with adult cardiometabolic risk factors. Data were drawn from the ongoing Cardiovascular Risk in Young Finns Study with seven follow-ups between 1980 and 2011 (baseline age 3–18 years, n = 1961). Physical activity data from a standardized questionnaire was expressed as a PA-index. Using the PA-index, four groups were formed: 1)persistently physically inactive (n = 246), 2)decreasingly active (n = 305), 3)increasingly active (n = 328), and 4)persistently active individuals (n = 1082). Adulthood cardiometabolic risk indicators included waist circumference, body mass index (BMI), blood pressure, and fasting lipids, insulin, and glucose. Clustered cardiometabolic risk was defined using established criteria for metabolic syndrome. Persistently physically inactive group was used as a reference. Compared to the persistently physically inactive group, those who were persistently active had lower risk for adult clustered cardiometabolic risk (RR = 0.67;CI95% = 0.53–0.84; Harmonized criteria), obesity (BMI > 30 kg/m2, RR = 0.76;CI95% = 0.59–0.98), high waist circumference (RR = 0.82;CI95% = 0.69–0.98), and high triglyceride (RR = 0.60;CI95% = 0.47–0.75), insulin (RR = 0.58;CI95% = 0.46–0.74) and glucose (RR = 0.77;CI95% = 0.62–0.96) concentrations as well as low high-density lipoprotein cholesterol (HDLsingle bondC) concentration (RR = 0.78;CI95% = 0.66–0.93). Comparable results were found when persistently physically inactive individuals were compared with those who increased PA. The results remained essentially similar after adjustment for education, diet, smoking, and BMI. Persistently physically inactive lifestyle since youth is associated with an unfavorable cardiometabolic risk profile in adulthood. Importantly, even minor increase in PA lowers the cardiometabolic risk. peerReviewed

Published
2021

176. Genetic association study of childhood aggression across raters, instruments, and age

Author

Nicholas G. Martin, S. Alexandra Burt, Louise Arseneault, Fazil Aliev, Luke M. Evans, Hill F. Ip, Beate St Pourcain, Michel G. Nivard, William E. Copeland, Rebecca K. Vinding, Scott Gordon, Koen Bolhuis, Christian J. Hopfer, Gun Peggy Knudsen, Stefan Johansson, Avshalom Caspi, Richard Border, Chandra A. Reynolds, Pål R. Njølstad, Liisa Keltikangas-Järvinen, Dorret I. Boomsma, Klaus Bønnelykke, Teemu Palviainen, Marta Ribasés, Alina Rodriguez, Catharina A. Hartman, Ilkka Seppälä, Christel M. Middeldorp, Rosa Bosch, Jan Haavik, Gail M. Williams, Andrea G. Allegrini, Ruth Ks, John R. B. Perry, Hadi Zafarmand, Chang Jiang, Elizabeth J. Costello, Camiel M. van der Laan, Olli T. Raitakari, Miquel Casas, Isabell Brikell, William G. Iacono, Jaakko Kaprio, John K. Hewitt, Andrew C. Heath, Eero Vuoksimaa, Xiaoran Tong, Gemma Español, Erik A. Ehli, Richie Poulton, Gareth E. Davies, Albertine J. Oldehinkel, Hans Bisgaard, Naomi R. Wray, Ted Reichborn-Kjennerud, Robert Plomin, Michael C. Stallings, Qing Lu, Jackob M. Najman, Daniel E. Adkins, Yi Lu, Harold Snieder, Sally J. Wadsworth, Alexander Neumann, Alexandra Havdahl, Karen Sugden, Kelly L. Klump, Andrew Smolen, Henrik Larsson, Toos C. E. M. van Beijsterveldt, Kenneth Krauter, Tarunveer S. Ahluwalia, Tellervo Korhonen, Andrey A. Shabalin, Joachim Heinrich, Anke R. Hammerschlag, Shelby Marrington, Lærke Sass, Pamela A. F. Madden, Henning Tiemeier, Tanja Vrijkotte, Paul Lichtenstein, Terho Lehtimäki, Ville Karhunen, Cristina Sánchez-Mora, Robin P. Corley, Anna A. E. Vinkhuyzen, Richard J. Rose, Per Magnus, Sabrina Llop, Ilja M. Nolte, S.A. Brown, Christian Hakulinen, Anjali K. Henders, Marie Standl, Silvia Alemany, Gretchen R.B. Saunders, Jouke-Jan Hottenga, Eveline L. de Zeeuw, Meike Bartels, Elisabeth Thiering, José J. Morosoli, Fiona A. Hagenbeek, Laura Pulkki-Råback, Frank C. Verhulst, Martin A. Kennedy, Craig E. Pennell, Eva Krapohl, Kaili Rimfeld, Tetyana Zayats, Lucía Colodro-Conde, Judith B.M. Ensink, André G. Uitterlinden, Natalia Vilor-Tejedor, Felix R. Day, Jennifer R. Harris, George Davey Smith, Qi Chen, Sebastian Lundström, Marjo-Riitta Järvelin, Alyce M. Whipp, Katrina L. Grasby, L. John Horwood, John Pearson, Judy L. Silberg, Paula Rovira, Hermine H. Maes, Carol A. Wang, Roseann E. Peterson, Tamara L. Wall, Andrew J. O. Whitehouse, Maria-Jose Lopez-Espinosa, Najaf Amin, Jess Tyrrell, Danielle M. Dick, Sarah E. Medland, Allison L. Miller, Øyvind Helgeland, Josep Antoni Ramos Quiroga, Joseph M. Boden, Abdullah Mamun, James Scott, María Soler Artigas, Joseph A. Prinz, Lindon J. Eaves, Terrie E. Moffitt, Matt McGue, Jordi Sunyer, Joanna Martin, Tampere University, Clinical Medicine, Department of Clinical Chemistry, Apollo-University Of Cambridge Repository, Ip, Hill F [0000-0003-1991-5019], Sánchez-Mora, Cristina [0000-0003-4211-1107], Nolte, Ilja M [0000-0001-5047-4077], St Pourcain, Beate [0000-0002-4680-3517], Palviainen, Teemu [0000-0002-7847-8384], Colodro-Conde, Lucía [0000-0002-9004-364X], Gordon, Scott [0000-0001-7623-328X], Aliev, Fazil [0000-0001-8357-4699], Karhunen, Ville [0000-0001-6064-1588], Border, Richard [0000-0002-6293-2968], Ahluwalia, Tarunveer S [0000-0002-7464-3354], Day, Felix R [0000-0003-3789-7651], Hottenga, Jouke-Jan [0000-0002-5668-2368], Rimfeld, Kaili [0000-0001-5139-065X], Lu, Yi [0000-0001-9933-3654], Soler Artigas, María [0000-0002-3213-1107], Bosch, Rosa [0000-0002-7596-183X], Ramos Quiroga, Josep Antoni [0000-0003-1622-0350], Neumann, Alexander [0000-0001-6653-3203], Grasby, Katrina [0000-0001-8539-0228], Middeldorp, Christel [0000-0002-6218-0428], Evans, Luke M [0000-0002-7458-1720], Alemany, Silvia [0000-0002-7925-6767], Sass, Lærke [0000-0002-5217-7014], Ruth, Kate [0000-0003-4966-9170], Ehli, Erik A [0000-0002-7865-3015], Hagenbeek, Fiona A [0000-0002-8773-0430], Snieder, Harold [0000-0003-1949-2298], Uitterlinden, André G [0000-0002-7276-3387], Haavik, Jan [0000-0001-7865-2808], Johansson, Stefan [0000-0002-2298-7008], Knudsen, Gun Peggy S [0000-0002-6193-4291], Njolstad, Pal Rasmus [0000-0003-0304-6728], Rodriguez, Alina [0000-0003-1209-8802], Brown, Sandy [0000-0001-8780-0323], Miller, Allison [0000-0003-3816-2251], Keltikangas-Järvinen, Liisa [0000-0002-7977-3852], Havdahl, Alexandra [0000-0002-9268-0423], Perry, John RB [0000-0001-6483-3771], Lehtimäki, Terho [0000-0002-2555-4427], Arseneault, Louise [0000-0002-2938-2191], Boden, Joseph [0000-0003-1502-1608], Pearson, John [0000-0001-5607-4517], Kennedy, Martin [0000-0002-6445-8526], Poulton, Richie [0000-0002-1052-4583], Copeland, William E [0000-0002-1348-7781], Wray, Naomi [0000-0001-7421-3357], Järvelin, Marjo-Riitta [0000-0002-2149-0630], McGue, Matt [0000-0002-5580-1433], Pennell, Craig E [0000-0002-0937-6165], Dick, Danielle M [0000-0002-1636-893X], Martin, Nicholas G [0000-0003-4069-8020], Medland, Sarah E [0000-0003-1382-380X], Kaprio, Jaakko [0000-0002-3716-2455], Tiemeier, Henning [0000-0002-4395-1397], Davey Smith, George [0000-0002-1407-8314], Oldehinkel, Albertine J [0000-0003-3925-3913], Ribasés, Marta [0000-0003-1039-1116], Lichtenstein, Paul [0000-0003-3037-5287], Plomin, Robert [0000-0002-0756-3629], Bartels, Meike [0000-0002-9667-7555], Nivard, Michel G [0000-0003-2015-1888], Boomsma, Dorret I [0000-0002-7099-7972], Apollo - University of Cambridge Repository, Life Course Epidemiology (LCE), Interdisciplinary Centre Psychopathology and Emotion regulation (ICPE), Child and Adolescent Psychiatry / Psychology, Epidemiology, Internal Medicine, Institute for Molecular Medicine Finland, Genetic Epidemiology, Helsinki Institute of Life Science HiLIFE, University of Helsinki, Tellervo Korhonen / Principal Investigator, Cognitive and Brain Aging, Faculty Common Matters (Faculty of Medicine), Medicum, Doctoral Programme in Cognition, Learning, Instruction and Communication, Department of Psychology and Logopedics, Helsinki Inequality Initiative (INEQ), Faculty Common Matters (Faculty of Education), Psychosocial factors and health, Behavioural Sciences, Department of Public Health, Adult Psychiatry, Epidemiology and Data Science, APH - Aging & Later Life, APH - Methodology, ARD - Amsterdam Reproduction and Development, Graduate School, Child Psychiatry, ACS - Pulmonary hypertension & thrombosis, ANS - Cellular & Molecular Mechanisms, ANS - Compulsivity, Impulsivity & Attention, Public and occupational health, APH - Health Behaviors & Chronic Diseases, Institut Català de la Salut, [Ip HF] Department of Biological Psychology, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands. [van der Laan CM] Department of Biological Psychology, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands. Netherlands Institute for the Study of Crime and Law Enforcement, Amsterdam, The Netherlands. [Krapohl EML] Institute of Psychiatry, Psychology and Neuroscience, King’s College London, London, UK. [Brikell I] Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden. [Sánchez-Mora C, Soler Artigas M, Rovira P, Ribasés M] Servei de Psiquiatria, Vall d’Hebron Hospital Universitari, Barcelona, Spain. Biomedical Network Research Centre on Mental Health (CIBERSAM), Instituto de Salud Carlos III, Barcelona, Spain. Unitat de Genètica Psiquiàtrica, Grup de Recerca en Psiquiatria, Salut Mental i Addicció, Vall d’Hebron Institut de Recerca (VHIR), Barcelona, Spain. Universitat Autònoma de Barcelona, Bellaterra, Spain. [Nolte IM] Department of Epidemiology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands. [Bosch R] Servei de Psiquiatria, Vall d’Hebron Hospital Universitari, Barcelona, Spain. Biomedical Network Research Centre on Mental Health (CIBERSAM), Instituto de Salud Carlos III, Barcelona, Spain. Servei de Psiquiatria i Medicina Legal, Universitat Autònoma de Barcelona, Bellaterra, Spain. [Español G] Servei de Psiquiatria, Vall d’Hebron Hospital Universitari, Barcelona, Spain. [Ramos Quiroga JA, Ribasés M] Servei de Psiquiatria, Vall d’Hebron Hospital Universitari, Barcelona, Spain. Biomedical Network Research Centre on Mental Health (CIBERSAM), Instituto de Salud Carlos III, Barcelona, Spain. Unitat de Genètica Psiquiàtrica, Grup de Recerca en Psiquiatria, Salut Mental i Addicció, Vall d’Hebron Institut de Recerca (VHIR), Barcelona, Spain. Universitat Autònoma de Barcelona, Bellaterra, Spain. Servei de Psiquiatria i Medicina Legal, Universitat Autònoma de Barcelona, Bellaterra, Spain, Vall d'Hebron Barcelona Hospital Campus, Biological Psychology, APH - Personalized Medicine, APH - Mental Health, Amsterdam Reproduction & Development, Perry, John R B [0000-0001-6483-3771], Ip, Hill F. [0000-0003-1991-5019], Nolte, Ilja M. [0000-0001-5047-4077], Ahluwalia, Tarunveer S. [0000-0002-7464-3354], Day, Felix R. [0000-0003-3789-7651], Evans, Luke M. [0000-0002-7458-1720], Ehli, Erik A. [0000-0002-7865-3015], Hagenbeek, Fiona A. [0000-0002-8773-0430], Uitterlinden, André G. [0000-0002-7276-3387], Knudsen, Gun Peggy S. [0000-0002-6193-4291], Perry, John R. B. [0000-0001-6483-3771], Copeland, William E. [0000-0002-1348-7781], Pennell, Craig E. [0000-0002-0937-6165], Dick, Danielle M. [0000-0002-1636-893X], Martin, Nicholas G. [0000-0003-4069-8020], Medland, Sarah E. [0000-0003-1382-380X], Oldehinkel, Albertine J. [0000-0003-3925-3913], Nivard, Michel G. [0000-0003-2015-1888], and Boomsma, Dorret I. [0000-0002-7099-7972]

Subjects
0301 basic medicine, DISORDER, 45/43, Genome-wide association study, 3124 Neurology and psychiatry, 0302 clinical medicine, Child, Psychiatry, 0303 health sciences, trastornos mentales [PSIQUIATRÍA Y PSICOLOGÍA], HERITABILITY, Mental Disorders, Cognition, Genomics, Explained variation, Justice and Strong Institutions, Aggression, Psychiatry and Mental health, Meta-analysis, ADOLESCENCE, Child, Preschool, conducta y mecanismos de la conducta::conducta::síntomas conductuales::agresión [PSIQUIATRÍA Y PSICOLOGÍA], 631/208/212, Female, Biological psychiatry, medicine.symptom, Life Sciences & Biomedicine, Investigative Techniques::Genetic Techniques::Genetic Association Studies [ANALYTICAL, DIAGNOSTIC AND THERAPEUTIC TECHNIQUES, AND EQUIPMENT], BEHAVIOR, RC321-571, Childhood aggression, Clinical psychology, SDG 16 - Peace, Adolescent, Mental Disorders [PSYCHIATRY AND PSYCHOLOGY], Neurosciences. Biological psychiatry. Neuropsychiatry, Single-nucleotide polymorphism, Biology, 3121 Internal medicine, Malalties mentals - Aspectes genètics, Genetic correlation, Article, 1117 Public Health and Health Services, Cellular and Molecular Neuroscience, 03 medical and health sciences, 631/477/2811, SDG 3 - Good Health and Well-being, Human behaviour, medicine, SNP, Humans, GENOME-WIDE ASSOCIATION, Biological Psychiatry, Genetic Association Studies, 030304 developmental biology, Genetic association, Retrospective Studies, técnicas de investigación::técnicas genéticas::estudios de asociación genética [TÉCNICAS Y EQUIPOS ANALÍTICOS, DIAGNÓSTICOS Y TERAPÉUTICOS], Science & Technology, SDG 16 - Peace, Justice and Strong Institutions, Infant, Behavior and Behavior Mechanisms::Behavior::Behavioral Symptoms::Aggression [PSYCHIATRY AND PSYCHOLOGY], 1103 Clinical Sciences, Agressivitat en els infants, Heritability, 030104 developmental biology, 1701 Psychology, ORIGINS, Research Programm of Donders Centre for Neuroscience, 3111 Biomedicine, TRAJECTORIES, 030217 neurology & neurosurgery, Demography, Genome-Wide Association Study
Abstract

Childhood aggressive behavior (AGG) has a substantial heritability of around 50%. Here we present a genome-wide association meta-analysis (GWAMA) of childhood AGG, in which all phenotype measures across childhood ages from multiple assessors were included. We analyzed phenotype assessments for a total of 328 935 observations from 87 485 children aged between 1.5 and 18 years, while accounting for sample overlap. We also meta-analyzed within subsets of the data, i.e., within rater, instrument and age. SNP-heritability for the overall meta-analysis (AGGoverall) was 3.31% (SE = 0.0038). We found no genome-wide significant SNPs for AGGoverall. The gene-based analysis returned three significant genes: ST3GAL3 (P = 1.6E–06), PCDH7 (P = 2.0E–06), and IPO13 (P = 2.5E–06). All three genes have previously been associated with educational traits. Polygenic scores based on our GWAMA significantly predicted aggression in a holdout sample of children (variance explained = 0.44%) and in retrospectively assessed childhood aggression (variance explained = 0.20%). Genetic correlations (rg) among rater-specific assessment of AGG ranged from rg = 0.46 between self- and teacher-assessment to rg = 0.81 between mother- and teacher-assessment. We obtained moderate-to-strong rgs with selected phenotypes from multiple domains, but hardly with any of the classical biomarkers thought to be associated with AGG. Significant genetic correlations were observed with most psychiatric and psychological traits (range $$\left| {r_g} \right|$$ r g : 0.19–1.00), except for obsessive-compulsive disorder. Aggression had a negative genetic correlation (rg = ~−0.5) with cognitive traits and age at first birth. Aggression was strongly genetically correlated with smoking phenotypes (range $$\left| {r_g} \right|$$ r g : 0.46–0.60). The genetic correlations between aggression and psychiatric disorders were weaker for teacher-reported AGG than for mother- and self-reported AGG. The current GWAMA of childhood aggression provides a powerful tool to interrogate the rater-specific genetic etiology of AGG.

Published
2021

177. Fatty liver index predicts incident risk of prediabetes, type 2 diabetes and non-alcoholic fatty liver disease (NAFLD)

Author

Eero Jokinen, Nina Hutri-Kähönen, Tomi Laitinen, Päivi Tossavainen, Jorma Viikari, Matthew A. Sabin, Markus Juonala, Costan G. Magnussen, Juha Koskinen, Emily Brown, Olli T. Raitakari, Daniel J. Cuthbertson, HYKS erva, HUS Children and Adolescents, Tampere University, Clinical Medicine, and Department of Paediatrics

Subjects
Male, RESONANCE-SPECTROSCOPY, obesity, ALANINE AMINOTRANSFERASE, Type 2 diabetes, Overweight, Gastroenterology, Body Mass Index, GLUCOSE, Endocrinology, 0302 clinical medicine, 3123 Gynaecology and paediatrics, Risk Factors, Prediabetes, Finland, risk, 2. Zero hunger, 0303 health sciences, Incidence, CARDIOVASCULAR RISK, Fatty liver, General Medicine, WEIGHT-GAIN, PREVALENCE, 3. Good health, Female, type 2 diabetes, medicine.symptom, Research Article, medicine.medical_specialty, 030209 endocrinology & metabolism, 3121 Internal medicine, VALIDATION, metabolic syndrome, Prediabetic State, 03 medical and health sciences, Internal medicine, medicine, Humans, HEPATIC STEATOSIS, Risk factor, 030304 developmental biology, OVERWEIGHT, business.industry, fungi, nutritional and metabolic diseases, non-alcoholic fatty liver disease, TRIGLYCERIDE CONTENT, medicine.disease, Obesity, Diabetes Mellitus, Type 2, 3121 General medicine, internal medicine and other clinical medicine, Metabolic syndrome, business, Body mass index, Non-alcoholic fatty liver disease
Abstract

AimsTo investigate the association between overweight/obesity and fatty liver index (FLI) on the odds of incident prediabetes/type 2 diabetes and non-alcoholic fatty liver disease (NAFLD) in 2020 participants after 10 years follow up.MethodsAt baseline (in 2001) 2020 participants, males and females, aged 24-39 years, were stratified according to body mass index (BMI), normal weight (2), overweight (≥25-2), or obese (≥30 kg/m2) and FLI (as high FLI ≥60 or low FLI Results514 and 52 individuals developed prediabetes and type 2 diabetes during follow-up. Such individuals were older, with higher BMI, serum glucose, insulin, alanine aminotransferase (ALT) and triglyceride (TG) concentrations than those who did not develop prediabetes or type 2 diabetes (n = 1454). The additional presence of high FLI significantly increased the risk of developing prediabetes and type 2 diabetes above the risk of being overweight/obese. Compared with normal weight, low FLI participants, the odds of prediabetes were ∼2-fold higher and the odds of type 2 diabetes were 9-10-fold higher respectively in the overweight/obese, high FLI group. No difference was observed between normal weight, low FLI and overweight/obese and low FLI groups.ConclusionsAn increased FLI significantly increases the odds of incident prediabetes, type 2 diabetes and NAFLD in individuals with overweight/obese highlighting the contributory role of liver fat accumulation in the pathophysiology of prediabetes/type 2 diabetes.Key messagesObesity is a risk factor for non-alcoholic fatty liver disease (NAFLD), prediabetes and type 2 diabetes.Additionally, NAFLD is more prevalent in people with prediabetes and type 2 diabetes when compared to age- and BMI-matched individuals.The presence of a raised fatty liver index (FLI) confers a significantly increased risk of developing prediabetes, type 2 diabetes and NAFLD above that conferred by being overweight/obese.The degree of elevation of FLI can risk stratify for incident prediabetes and type 2 diabetes in people with obesity.

Published
2021

178. Impedance plethysmography-based method in the assessment of subclinical atherosclerosis

Author

Mikko Peltokangas, Mira Haapala, Teemu Koivistoinen, Niku Oksala, Mika Kähönen, Antti Vehkaoja, Olli T. Raitakari, Leo-Pekka Lyytikäinen, Terho Lehtimäki, Matti Mäntysalo, Mika-Matti Laurila, Nina Hutri-Kähönen, Tampere University, Clinical Medicine, Department of Clinical Chemistry, TAYS Heart Centre, BioMediTech, Kanta-Häme Central Hospital Hämeenlinna, Department of Clinical Physiology and Nuclear Medicine, Department of Paediatrics, Electrical Engineering, and Verisuoni- ja toimenpideradiologinen keskus

Subjects
0301 basic medicine, Adult, medicine.medical_specialty, 030204 cardiovascular system & hematology, Pulse Wave Analysis, 3121 Internal medicine, Carotid Intima-Media Thickness, 03 medical and health sciences, 0302 clinical medicine, Risk Factors, Internal medicine, medicine.artery, medicine, Plethysmograph, Pulse wave, Humans, Plethysmography, Impedance, cardiovascular diseases, Brachial artery, Carotid artery distensibility, Finland, Framingham Risk Score, business.industry, Pulse (signal processing), Atherosclerosis, 3126 Surgery, anesthesiology, intensive care, radiology, 030104 developmental biology, Intima-media thickness, Subclinical atherosclerosis, Cardiology, cardiovascular system, Cardiology and Cardiovascular Medicine, business, circulatory and respiratory physiology
Abstract

Background and aims The aim of this study was to examine an association of individual and combined pulse waveform parameters derived from bioimpedance measurements, that is pulse waves from a distal impedance plethysmographic (IPG), a whole-body impedance cardiographic (ICG) and transformed distal impedance plethysmographic (tIPG) signals, with markers of subclinical atherosclerosis, i.e. carotid intima-media thickness (cIMT), brachial artery flow-mediated dilation (FMD) and carotid artery distensibility (Cdist). The level of the association was also compared for arterial pulse wave velocity (PWV) and cIMT, FMD, and Cdist. Methods IPG, ICG, tIPG signals were measured from 1741 Finnish adults aged 30–45 years. The association between pulse wave parameters and cIMT, FMD and Cdist was studied using bootstrapped stepwise Akaike's Information Criterion method resulting in selection of parameters other than PWV, i.e. parameters having stronger association with cIMT, FMD and Cdist than PWV, in the model. Then risk scores were calculated from the selected pulse wave parameters and their association between cIMT, FMD and Cdist was studied with multivariable linear regression analysis. Results The risk score was found to be the third strongest predictor of subclinical atherosclerosis as indicated by cIMT measurement, the second strongest predictor of FMD and the strongest predictor of Cdist. These findings show that several individual pulse wave parameters were associated more strongly with cIMT, FMD, and Cdist than PWV when adjusted with clinical risk factors. Conclusions Impedance based pulse waveform analysis provides a useful tool for assessing cardiovascular risk and estimating presence of structural changes in the vasculature. publishedVersion

Published
2021

179. Meta-analysis uncovers genome-wide significant variants for rapid kidney function decline

Author

Lukas Habegger, Charumathi Sabanayagam, Michael Preuss, Laura M. Raffield, Mary F. Feitosa, Bamidele O. Tayo, Kevin Ho, Leo-Pekka Lyytikäinen, Florian Kronenberg, Valencia Hui Xian Foo, Adrienne Tin, Michael Cantor, Nisha Bansal, Tarunveer S. Ahluwalia, Melanie Waldenberger, Sarah A. Pendergrass, Behrooz Z. Alizadeh, Wolfgang Koenig, Qiong Yang, Xiaodong Bai, Christoph Wanner, Ben Schöttker, Giovanni Coppola, A. R. Shuldiner, Leslie A. Lange, Piyush Gampawar, Markus Scholz, Tien Yin Wong, Mary L. Biggs, Morris Swertz, Alicia Hawes, Girish N. Nadkarni, Christina-Alexandra Schulz, Chiea Chuen Khor, Ricardo H. Ulloa, Jeffrey C. Staples, Miao-Li Chee, Laura M. Yerges-Armstrong, Andrew Blumenfeld, Karlhans Endlich, Bernhard Banas, Bruce H.R. Wolffenbuttel, Kai-Uwe Eckardt, Pavel Hamet, Carsten A. Böger, Harold Snieder, Marcus B. Jones, Judy Wang, Shih-Jen Hwang, Mathias Gorski, Anselm Hoppmann, Josyf C. Mychaleckyj, Bernd Holleczek, Pamela R. Matias-Garcia, Rainer Rettig, Karsten B. Sieber, Manasi Pradhan, Pashupati P. Mishra, Peter Rossing, Matthias Wuttke, Miao-Ling Chee, H. Marike Boezen, Yong Li, M. Arfan Ikram, Jeffrey G. Reid, Teresa Nutile, Maria Sotiropoulos Padilla, Lude Franke, Robert J. Carroll, Luca A. Lotta, Bernhard K. Krämer, Kjell Nikus, Jerome I. Rotter, Thomas Meitinger, Lars Wallentin, Cisca Wijmenga, Kent D. Taylor, Holly Kramer, Louis Widom, Olli T. Raitakari, Marcus E. Kleber, Man Li, Nina Hutri-Kähönen, Massimiliano Cocca, Reinhold Schmidt, John D. Overton, Cristian Pattaro, Michael Lattari, Sarah E. Wolf, Jin-Fang Chai, Karina Toledo, Brigitte Kühnel, Zhenhua Gu, Peter Almgren, Caitlin Forsythe, Yuri Milaneschi, Stephan J. L. Bakker, Layal Chaker, Dawn M. Waterworth, Silke Szymczak, James G. Wilson, Peter J. van der Most, Michelle L. O'Donoghue, William Salerno, Masayuki Yasuda, Sahar Ghasemi, Eric Boerwinkle, Josef Coresh, Ilja M. Nolte, Kia Manoochehri, Konstantin Strauch, Thomas D. Schleicher, Myriam Rheinberger, Audrey Y. Chu, Sanaz Sedaghat, Sandra Freitag-Wolf, Boting Ning, Matthias Nauck, Christina Beechert, Helena Schmidt, Harvey D. White, Nina Mononen, Johanne Tremblay, Navya Shilpa Josyula, Mika Kähönen, Katrin Horn, Andre Franke, Marianne Rots, Bettina Jung, Alexander R. Rosenkranz, Christian M. Shaffer, Mary Ann Lukas, Gerjan Navis, Christian Gieger, John Chalmers, Shareef Khalid, Uwe Völker, Marju Orho-Melander, Iris M. Heid, Brenda W.J.H. Penninx, A. Baras, Alexander Lopez, Evan Maxwell, Ruth J. F. Loos, Erin D. Fuller, Christa Meisinger, Gonçalo R. Abecasis, Suganthi Balasubramanian, Chris H. L. Thio, Martin H. de Borst, Stefan Coassin, Ching-Yu Cheng, Wolfgang Lieb, Kenneth Rice, Alexander Teumer, Mark Woodward, Gisu Eom, Hermann Brenner, Thomas W. Winkler, Anna Köttgen, Edith Hofer, Aris Economides, Ron T. Gansevoort, Pim van der Harst, Lyndon J. Mitnaul, Bruce M. Psaty, Erwin P. Bottinger, Olle Melander, Niek Verweij, Frauke Degenhardt, Yan Zhang, Mohsen Ghanbari, Veronika Wanner, Terho Lehtimäki, Leland Barnard, Tampere University, Primary Health Care, Department of Paediatrics, Clinical Medicine, Department of Clinical Physiology and Nuclear Medicine, Department of Clinical Chemistry, TAYS Heart Centre, Groningen Institute for Organ Transplantation (GIOT), Groningen Kidney Center (GKC), Cardiovascular Centre (CVC), Life Course Epidemiology (LCE), Department of Marketing Management, Epidemiology, Internal Medicine, Psychiatry, Amsterdam Neuroscience - Complex Trait Genetics, Amsterdam Neuroscience - Mood, Anxiety, Psychosis, Stress & Sleep, APH - Mental Health, and APH - Digital Health

Subjects
0301 basic medicine, medicine.medical_specialty, Genome-wide association study, 030232 urology & nephrology, Protein Disulfide-Isomerases, Hasso-Plattner-Institut für Digital Engineering GmbH, Renal function, Locus (genetics), Biology, AMP-Activated Protein Kinases, Kidney, 3121 Internal medicine, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, end-stage kidney disease, rapid eGFRcrea decline, Urologi och njurmedicin, medicine, Humans, Urology and Nephrology, ddc:610, Allele, Genetic association, Genetics, Creatinine, genome-wide association study, Acute kidney injury, acute kidney injury, medicine.disease, United Kingdom, ddc, 030104 developmental biology, chemistry, Nephrology, Medical genetics, 3111 Biomedicine, 610 Medizin und Gesundheit, Glomerular Filtration Rate
Abstract

Rapid decline of glomerular filtration rate estimated from creatinine (eGFRcrea) is associated with severe clinical endpoints. In contrast to cross-sectionally assessed eGFRcrea, the genetic basis for rapid eGFRcrea decline is largely unknown. To help define this, we meta-analyzed 42 genome-wide association studies from the Chronic Kidney Diseases Genetics Consortium and United Kingdom Biobank to identify genetic loci for rapid eGFRcrea decline. Two definitions of eGFRcrea decline were used: 3 mL/min/1.73m(2)/year or more ("Rapid3"; encompassing 34,874 cases, 107,090 controls) and eGFRcrea decline 25% or more and eGFRcrea under 60 mL/min/1.73m(2) at follow-up among those with eGFRcrea 60 mL/min/1.73m(2) or more at baseline ("CKDi25"; encompassing 19,901 cases, 175,244 controls). Seven independent variants were identified across six loci for Rapid3 and/or CKDi25: consisting of five variants at four loci with genome-wide significance (near UMOD-PDILT (2), PRKAG2, WDR72, OR2S2) and two variants among 265 known eGFRcrea variants (near GATM, LARP4B). All these loci were novel for Rapid3 and/or CKDi25 and our bioinformatic follow-up prioritized variants and genes underneath these loci. The OR2S2 locus is novel for any eGFRcrea trait including interesting candidates. For the five genome-wide significant lead variants, we found supporting effects for annual change in blood urea nitrogen or cystatin-based eGFR, but not for GATM or (LARP4B). Individuals at high compared to those at low genetic risk (8-14 vs. 0-5 adverse alleles) had a 1.20-fold increased risk of acute kidney injury (95% confidence interval 1.08-1.33). Thus, our identified loci for rapid kidney function decline may help prioritize therapeutic targets and identify mechanisms and individuals at risk for sustained deterioration of kidney function., Zweitveröffentlichungen der Universität Potsdam : Reihe der Digital Engineering Fakultät; 19

Published
2021

180. Uncovering the shared lipidomic markers of subclinical osteoporosis-atherosclerosis comorbidity: The Young Finns Study

Author

Harri Sievänen, Binisha H. Mishra, Mika Hilvo, Marika Laaksonen, Pashupati P. Mishra, Mika Kähönen, Nina Mononen, Nina Hutri-Kähönen, Reijo Laaksonen, Terho Lehtimäki, Jorma Viikari, Markus Juonala, Olli T. Raitakari, Tampere University, Clinical Medicine, Department of Clinical Chemistry, Department of Paediatrics, and Department of Clinical Physiology and Nuclear Medicine

Subjects
Male, 0301 basic medicine, Histology, Physiology, Endocrinology, Diabetes and Metabolism, Osteoporosis, 030209 endocrinology & metabolism, Comorbidity, 3121 Internal medicine, Carotid Intima-Media Thickness, 03 medical and health sciences, 0302 clinical medicine, Risk Factors, Lipidomics, medicine, Humans, Quantitative computed tomography, Finland, Subclinical infection, medicine.diagnostic_test, business.industry, Atherosclerosis, medicine.disease, Omics, 030104 developmental biology, Cohort, Female, 3111 Biomedicine, business, Body mass index, Biomarkers
Abstract

Background: Osteoporosis and atherosclerosis are complex multifactorial diseases sharing common risk factors and pathophysiological mechanisms suggesting that these are comorbidities. Omics studies identifying joint molecular markers associated with these diseases are sparse. Subjects and methods: Using liquid chromatography-tandem mass spectrometry, we quantified 437 molecular lipid species from the Young Finns Study cohort (aged 30–45 years and 57% women) and performed lipidome-wide multivariate analysis of variance (MANOVA) with early markers for both diseases. Carotid intima-media thickness for atherosclerosis measured with ultrasound and bone mineral density from distal radius and tibia for osteoporosis measured with peripheral quantitative computed tomography were used as early markers of the diseases. Results: MANOVA adjusted with age, sex and body mass index, identified eight statistically significant (adjusted p-value (padj) < 0.05) and 15 suggestively significant (padj < 0.25) molecular lipid species associated with the studied markers. Similar analysis adjusted additionally for smoking habit, physical activity and alcohol consumption identified four significant and six suggestively significant molecular lipid species. These most significant lipid classes/species jointly associated with the studied markers were glycerolipid/TAG(18:0/18:0/18:1), glycerophospholipid/PC(40:3), sphingolipid/Gb3(d18:1/22:0), and sphingolipid/Gb3(d18:1/24:0). Conclusion: Our results support the osteoporosis-atherosclerosis comorbidity hypothesis and present potential new joint lipid biomarkers for these diseases. publishedVersion

Published
2021
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181. Birth weight and adult income : An examination of mediation through adult height and body mass

Author

Olli T. Raitakari, Terho Lehtimäki, Petri Böckerman, Jutta Viinikainen, Jaana T. Kari, Jaakko Pehkonen, Tampere University, Department of Clinical Chemistry, and Clinical Medicine

Subjects
Adult, Male, tulot, Mediation (statistics), Birth weight, vaikutukset, tulotaso, body mass index, pituuskasvu, sosioekonominen asema, Body Mass Index, polygenic instrument, pituus, Birth Weight, Humans, Medicine, mediation, syntymäpaino, Longitudinal Studies, painoindeksi, Socioeconomic status, sosioekonomiset tekijät, business.industry, Health Policy, Body Weight, birth weight, Anthropometry, 3142 Public health care science, environmental and occupational health, Body Height, Adult height, Causality, income, Income, Female, 3111 Biomedicine, multivariable Mendelian randomization, business, Body mass index, Demography, height
Abstract

This paper examines the causal links between early human endowments and socioeconomic outcomes in adulthood. We use a genotyped longitudinal survey (Cardiovascular Risk in Young Finns Study) that is linked to the administrative registers of Statistics Finland. We focus on the effect of birth weight on income via two anthropometric mediators: body mass index (BMI) and height in adulthood. We find that (i) the genetic instruments for birth weight, adult height, and adult BMI are statistically powerful; (ii) there is a robust total effect of birth weight on income for men but not for women; (iii) the total effect of birth weight on income for men is partly mediated via height but not via BMI; and (iv) the share of the total effect mediated via height is substantial, of approximately 56%. publishedVersion

Published
2021

182. Influence of early life risk factors and lifestyle on systemic vascular resistance in later adulthood : the cardiovascular risk in young Finns study

Author

Markus Juonala, Emilia Kähönen, Mika Kähönen, Nina Hutri-Kähönen, Heikki Aatola, Atte Haarala, Olli T. Raitakari, Terho Lehtimäki, Kalle Sipilä, Tampere University, Tays Research Services, Department of Clinical Physiology and Nuclear Medicine, Clinical Medicine, Department of Clinical Chemistry, and Primary Health Care

Subjects
Adult, medicine.medical_specialty, Adolescent, Cardiac index, Hemodynamics, Blood Pressure, 3121 Internal medicine, Body Mass Index, Young Adult, Risk Factors, Internal medicine, Internal Medicine, medicine, Humans, Risk factor, Child, Life Style, Finland, medicine.diagnostic_test, business.industry, General Medicine, 3126 Surgery, anesthesiology, intensive care, radiology, Impedance cardiography, Blood pressure, medicine.anatomical_structure, Cardiovascular Diseases, Heart Disease Risk Factors, Cohort, Vascular resistance, Female, Vascular Resistance, 3111 Biomedicine, Cardiology and Cardiovascular Medicine, business, Body mass index
Abstract

Purpose: There are limited data available concerning the effects of lifetime risk factors and lifestyle on systemic hemodynamics, especially on systemic vascular resistance. The purpose of the study was to evaluate how lifetime cardiovascular risk factors (body mass index (BMI), high-density lipoprotein, low-density lipoprotein, triglycerides, systolic blood pressure, blood glucose) and lifestyle factors (vegetable consumption, fruit consumption, smoking and physical activity) predict systemic vascular resistance index (SVRI) and cardiac index (CI) assessed in adulthood. Materials and Methods: Our study cohort comprised 1635 subjects of the Cardiovascular Risk in Young Finns Study followed up for 27 years since baseline (1980; aged 3–18 years, females 54.3%) who had risk factor and lifestyle data available since childhood. Systemic hemodynamics were measured in 2007 (aged 30–45 years) by whole-body impedance cardiography. Results: In the multivariable regression analysis, independent predictors of the adulthood SVRI were childhood BMI, blood glucose, vegetable consumption, smoking, and physical activity (p ≤.046 for all). Vegetable consumption, smoking, and physical activity remained significant when adjusted for corresponding adult data (p ≤.036 for all). For the CI, independent predictors in childhood were BMI, systolic blood pressure, vegetable consumption, and physical activity (p ≤.044 for all), and the findings remained significant after adjusting for corresponding adult data (p ≤.046 for all). The number of childhood and adulthood risk factors and unfavourable lifestyle factors was directly associated with the SVRI (p

Published
2021

183. The Role of Inflammatory Cytokines as Intermediates in the Pathway from Increased Adiposity to Disease

Author

Ilkka Seppälä, Aarno Palotie, Niina Pitkänen, Aki S. Havulinna, Nicholas J. Timpson, Marita Kalaoja, Leo-Pekka Lyytikäinen, Veikko Salomaa, Mika Kähönen, Sirpa Jalkanen, Laura J Corbin, Mikael Maksimow, Vanessa Y Tan, Markus Perola, Terho Lehtimäki, Johannes Kettunen, Samuli Ripatti, Emma Raitoharju, Ari Ahola-Olli, Kristiina Santalahti, Marko Salmi, Jorma S. A. Viikari, Olli T. Raitakari, Tampere University, Department of Clinical Chemistry, Clinical Medicine, Department of Clinical Physiology and Nuclear Medicine, Institute for Molecular Medicine Finland, Genomics of Neurological and Neuropsychiatric Disorders, University of Helsinki, Centre of Excellence in Complex Disease Genetics, Department of Public Health, Samuli Olli Ripatti / Principal Investigator, Complex Disease Genetics, Biostatistics Helsinki, Research Programs Unit, and Aarno Palotie / Principal Investigator

Subjects
Endocrinology, Diabetes and Metabolism, medicine.medical_treatment, Medicine (miscellaneous), Context (language use), Disease, 3121 Internal medicine, Proinflammatory cytokine, Body Mass Index, Cohort Studies, 03 medical and health sciences, 0302 clinical medicine, Endocrinology, Mendelian randomization, medicine, Humans, 030212 general & internal medicine, Obesity, 030304 developmental biology, Adiposity, 0303 health sciences, Nutrition and Dietetics, business.industry, Epidemiology/Genetics, Odds ratio, Original Articles, 3. Good health, Cytokine, 3121 General medicine, internal medicine and other clinical medicine, Immunology, Cytokines, Tumor necrosis factor alpha, Original Article, ICEP, 3111 Biomedicine, business, Body mass index
Abstract

ObjectiveThis study aimed to investigate the role of cytokines as intermediates in the pathway from increased adiposity to disease.MethodsBMI and circulating levels of up to 41 cytokines were measured in individuals from three Finnish cohort studies (n = 8,293). Mendelian randomization (MR) was used to assess the impact of BMI on circulating cytokines and the impact of BMI‐driven cytokines on risk of obesity‐related diseases.ResultsObservationally, BMI was associated with 19 cytokines. For every SD increase in BMI, causal effect estimates were strongest for hepatocyte growth factor, monocyte chemotactic protein‐1 (MCP‐1), and tumor necrosis factor–related apoptosis‐inducing ligand (TRAIL) and were as ratios of geometric means 1.13 (95% CI: 1.08‐1.19), 1.08 (95% CI: 1.04‐1.14), and 1.13 (95% CI: 1.04‐1.21), respectively. TRAIL was associated with a small increase in the odds of coronary artery disease (odds ratio: 1.03; 95% CI: 1.00‐1.06). There was inconsistent evidence for a protective role of MCP‐1 against inflammatory bowel diseases.ConclusionsObservational and MR estimates of the effect of BMI on cytokine levels were generally concordant. There was little evidence for an effect of raised levels of BMI‐driven cytokines on disease. These findings illustrate the challenges of MR when applied in the context of molecular mediation.

Published
2021

184. Heterogeneous contributions of change in population distribution of body mass index to change in obesity and underweight

Author

Maryam Sharafkhah, Emanuel Zitt, Majid Ezzati, Luxia Zhang, Young-Ho Khang, Ellina Rakhimova, Kairit Mikkel, Tiina Vlasoff, Eruke E. Egbagbe, Sidsel Graff-Iversen, Ilona Nenko, Magdalena Klimek, Mathilde Savy, Sanjib Kumar Sharma, Alfonso Siani, Luís Lopes, Vanina Bongard, Gregor Jurak, Jacqueline F. Price, Christina-Paulina Lambrinou, Maria Lc Iurilli, Rainford J. Wilks, Bontha V. Babu, Fereidoun Azizi, Harunobu Nakamura, Marialaura Bonaccio, Angela Döring, Zhenyu Zhang, Naser Ahmadi, Jolanta Słowikowska-Hilczer, Ana Paula Carlos Cândido, Clive Osmond, Thirunavukkarasu Sathish, Robert J. Adams, Themistoklis Tzotzas, Reina Engle-Stone, Atul Trivedi, Shoichiro Tsugane, Niels Møller, Jorge Bezerra, Dénes Molnár, Muhammad Fadhli Mohd Yusoff, Badreya Al-Lahou, J. Jaime Miranda, Bahram Mohajer, Sigmund A. Anderssen, Lital Keinan Boker, Eero Kajantie, Martin Gulliford, Maties Torrent, Sumit Bharadwaj, Toshiharu Ninomiya, Zbigniew Gaciong, Nayu Ikeda, Li Juan Wu, Adrian Richter, Licia Iacoviello, Marc J. Gunter, Wenbin Wei, Norsyamlina Che Abdul Rahim, Eman Aly, Ambady Ramachandran, Nils Lehmann, Soile E. Puhakka, Giovanni Veronesi, Hongsheng Bi, Eiji Oda, Jia Li Duan, Per Tynelius, José María Huerta, Janne Schurmann Tolstrup, Rodrigo M. Carrillo-Larco, Rosangela Fernandes Lucena Batista, Victoria E Soto-Rojas, Hanno Ulmer, Shukri F. Mohamed, Anthony Kafatos, Suyeon Park, Mohsen Ibrahim, Hamed Pouraram, Bin Zhou, May Soe Aung, Lars Bo Andersen, Erfan Ghasemi, René Charles Sylva, Himanshu K. Chaturvedi, Luc Dauchet, Ahmad Ali Zainuddin, Angela Chetrit, Dan Zhu, Valérie Deschamps, Ko Ko Zaw, Peter Vollenweider, Tomas Vega, Yves Martin-Prével, Mahfuzar Rahman, Dorja Vočanec, Roman Topor-Madry, Vinay Nangia, Herculina S. Kruger, Asher Fawwad, Emily Sonestedt, Elena Pahomova, Aleksander Giwercman, Elżbieta Dziankowska-Zaborszczyk, Cecilia Björkelund, Tatjana Hejgaard, Maria Puiu, Maria Benedetta Donati, Andrew Wong, Carlos P. Boissonnet, Santosh K. Bhargava, Patrick Kolsteren, Dermot O'Reilly, Bahareh Kheiri, Wolfgang Kratzer, Susanne R. de Rooij, H. Bas Bueno-de-Mesquita, Günther Fink, José R. Banegas, Michele Monroy-Valle, Drude Molbo, Mahmudur Rahman, Hynek Pikhart, Rafael N. Pichardo, Massimo Salvetti, Hui Cai, Sarah Filippi, Georg Posch, Hung-Kwan So, Yonghua Hu, Katsuyasu Kouda, Joana Carvalho, Gailute Bernotiene, Hannu Uusitalo, Thein Thein Htay, Felix Kaducu, Maigeng Zhou, Lars Ängquist, Thi Tuyet-Hanh Tran, Charles Lunogelo, Michel Joffres, Sabina Zambon, Ronald D. Gregor, Vayia Rarra, Seyed Mohammad Hashemi-Shahri, Loreto Santa Marina, Galina Obreja, Rudolf Kaaks, Aya Mostafa, Maria do Carmo Franco, Beata Gurzkowska, Chien-Jen Chen, Marie Moitry, Nizal Sarrafzadegan, Xiangjun Wang, Diego Giulliano Destro Christofaro, Imperia Brajkovich, Fangfang Chen, Francesco Panza, Ling Yang, Holly E. Syddall, Cecily Kelleher, Michael Tornaritis, Ningli Wang, Lutgarde Thijs, Marjolein Visser, Angelika Schaffrath Rosario, María José Tormo, Jostein Steene-Johannessen, Norbert Amougou, Emmanuella Magriplis, Mar Alvarez-Pedrerol, Jingli Gao, Stig E. Bojesen, Giuseppe Grosso, Seongjun Ha, Lauren Lissner, Mikhail Benet, Anastasia Markaki, Sanjay Rampal, Antônio Augusto Moura da Silva, Maria Lorenza Muiesan, Angelique Chan, Yvonne T. van der Schouw, Annamari Lundqvist, Philippe Amouyel, Kristyna Zejglicova, Charalambos Hadjigeorgiou, João Breda, Jørgen Meisfjord, Fatima Zahra Laamiri, Carl Lachat, Kai-Uwe Saum, Vilma Irazola, Leng Huat Foo, Óscar Lopes, Dickman Gareta, Flavio Nervi, Imre Janszky, Ruzena Kubinova, Terho Lehtimäki, Mario V. Capanzana, Moyses Szklo, Ramfis Nieto-Martínez, Viswanathan Mohan, Shuohua Chen, Arvind Pandey, Luigi Palmieri, Roya Kelishadi, Srinivasan Kannan, Jie Mi, Robert Beaglehole, Liliana Dacica, Jyrki K. Virtanen, Mohan Deepa, Peter Ueda, Isti Ilmiati Fujiati, Hermann Pohlabeln, Morten Sodemann, Jytte Halkjær, Zbigniew Kułaga, Sophie Visvikis-Siest, Farshad Farzadfar, Mohsen Azimi-Nezhad, Henry Völzke, Karolina Milkowska, Zahra Mohammadi, Belgin Ünal, Magda Gasull, George S. Stergiou, Marshall K. Tulloch-Reid, Seppo Koskinen, James E. Bennett, Marcela González-Gross, Virginija Dulskiene, Idris Guessous, Assembekov Batyrbek, Kamarul Imran Musa, Jeannette Lee, Josep Redon, Bihungum Bista, Luisa M Macieira, Johan Sundström, Andres Metspalu, Lariane M Ono, Flora A. Ukoli, Salar Rahimikazerooni, Andrea Gualtieri, Trevor S. Ferguson, Félicité Tchibindat, Eliza Cinteza, Ha Tp Do, Tajana Zeljkovic Vrkic, Tuyen D Le, Alison J. Hayes, Abdul Basit, Chandini Nekkantti, Teresa Norat, Eunice Ugel, Gulmira Aitmurzaeva, Mariachiara Di Cesare, Abdul Hamid Zargar, Vincenzo Solfrizzi, Garry L. Jennings, Aline Meirhaeghe, Kaare Christensen, Päivi Mäki, Xu Lin, Ali Esmaeili, Joanna Baran, Aneta Grajda, Renata Cifkova, Alexandre C. Pereira, Martin Bobak, Iuliia A Rusakova, Keiu Nelis, Damian K Francis, Guansheng Ma, Axel C. Carlsson, Alejandro Diaz, Alireza Ansari-Moghaddam, N Capkova, Zumin Shi, Maria Turley, Imelda A. Agdeppa, Helena I. S. Nogueira, Marcia Scazufca, Katharina Maruszczak, Natascia Rinaldo, Paulo A. Lotufo, Nuno Lunet, Thor Aspelund, Caroline H.D. Fall, Antonio Cabrera de León, Ahmad Faudzi Yusoff, Holger Theobald, Beatriz D'Agord Schaan, Pedro Marques-Vidal, William A. Neal, Mihai Gafencu, Tandi E. Matsha, Ana B. Crujeiras, Ahmad Reza Dorosty, Alain Morejon, Weili Yan, Dominique Hange, Bekbolat Zholdin, Frédéric Gottrand, Jorge Mota, Jana Námešná, Stevo Popovic, Louise Eriksen, Line Lund Kårhus, Cihangir Erem, Juergen Breckenkamp, Mathilde Kersting, Yi Song, Martin McKee, Aleksandra Gomula, Rafaela Rosário, Enzo Manzato, S. Goya Wannamethee, Sounnia Mediene Benchekor, Azim Nejatizadeh, Krishna Kumar Aryal, Juan P. González-Rivas, Vedrana Sember, Stephen T. McGarvey, Jukka T. Salonen, Patrick Pasquet, Patricia Varona-Pérez, Amelia C. Crampin, Ramin Heshmat, Violeta Iotova, Juvenal Soares Dias-da-Costa, Oye Gureje, Aletta E. Schutte, João Luiz Bastos, Anelise Reis Gaya, Konrad Jamrozik, Dalia Luksiene, Amina Barkat, Maria Paula Santos, José Camolas, Azli Baharudin, Diego Vanuzzo, Doris Stöckl, Rosalynn Siantar, Jouko Saramies, Albertino Damasceno, Davood Khalili, Simona Bo, Martina Müller-Nurasyid, Dominique Cottel, Markku Peltonen, Fikru Tullu, Ana Isabel Rito, Angélica Ochoa-Avilés, Annette J. Dobson, Christopher T. Cowell, Charumathi Sabanayagam, Rildo de Souza Wanderley Júnior, Oanh T. H. Trinh, Farahnaz Joukar, Mostafa K. Mohamed, Mostafa Qorbani, Jeongseon Kim, Helmut Schröder, Machi Suka, Natasja M. van Schoor, Jussi Kauhanen, Teresa Haugsgjerd, Goodarz Danaei, M. Fernanda Lima-Costa, Yong Tao, Elisabetta L. Romeo, Grazyna Jasienska, Victor Guillermo Sequera, Kazem Mohammad, Yanina Zócalo, Fernanda Cunha Soares, Jianfeng Wu, Mohammad Esmaeel Motlagh, María Elena Díaz-Sánchez, Monika Zuziak, Eldridge Ferrer, Anette Varbo, Leila Beltrami Moreira, Jeremy M. Jacobs, Kenneth James, Elena Sacchini, Pascal Bovet, Mahboubeh Parsaeian, Tania Lopez, Ya Xing Wang, Wojciech Drygas, Jody C Miller, Svetlana A. Shalnova, Maria Elisa Zapata, Chung T Nguyen, Nimmathota Arlappa, Edwige Landais, Thorkild I. A. Sørensen, Jeannette Klimont, Amirabbas Momenan, Erik J. Timmermans, Mari-Liis Tammesoo, Jost B. Jonas, Stefania Toselli, Maria Teresa Anselmo Olinto, Bahman Cheraghian, Kouamelan Doua, Esteban Carmuega, Marjeta Mišigoj-Duraković, Bo Werner, M. Arfan Ikram, Breige A. McNulty, Christa Meisinger, Clara Homs, Namuna Shrestha, Alina Kerimkulova, Youcef Laid, Claes Ohlsson, Alicia Matijasevich, Alison J Price, Ala'a Alkerwi, Kristine H. Allin, Lorenza Pilotto, Mohannad Al Nsour, Ingunn Holden Bergh, Marianna Noale, Heba Fouad, Vilnis Dzerve, Novie O. Younger-Coleman, Peter Willeit, Andrea R. V. R. Horimoto, Freda Pitakaka, Habiba Ben Romdhane, Savvas C. Savva, Rajeev Gupta, Jennifer Servais, Cristina Padez, Sarah P. Garnett, Maria del Cristo Rodriguez-Perez, Michala Lustigová, Tien Yin Wong, Rosa Haghshenas, Jonathan Giovannelli, Christina Howitt, Marleen E. Hendriks, Fadia AlBuhairan, Huashuai Chen, Gretchen A Stevens, Luís B. Sardinha, David Goltzman, Jenny M. Kindblom, Karina Mary de Paiva, Yousef Khader, Eric Monterrubio-Flores, Rajendra Pradeepa, Yi-Ting Lin, Martin Neovius, Juan Francisco Miquel, Ellis Owusu-Dabo, Anil Poudyal, Marzieh Katibeh, Tanja Stocks, Veronica Mocanu, Ulla Roggenbuck, Robespierre Ribeiro, Gabriele Eiben, Mary Simon, Christine Cameron, Hamid Hakimi, Kamel Ajlouni, Jakub Stokwiszewski, Iulia Jurca Simina, Pietro Amedeo Modesti, Frederick C. W. Wu, Peter Kristensen, Charles Mondo, Felix Gutzwiller, Mariana Sbaraini, Martijn Huisman, Betina H. Thuesen, Queenie Chan, Antonisamy Belavendra, Artur Mazur, Ulf Ekelund, Laura A. Rodríguez-Villamizar, Marcos André Moura-dos-Santos, Jean Ferrières, Farhad Zamani, Shina Avi, Yves Kameli, Luis Paulo Gomes Mascarenhas, Aluísio J D Barros, Thomas Meinertz Dantoft, Hossein Poustchi, Farid Najafi, Giovanni de Gaetano, Azaliia M Tuliakova, Vera Lanska, Tint Swe Latt, Matthias Bopp, Abbas Rezaianzadeh, Rod Jackson, Johan Van der Heyden, Reecha Sofat, Koen Van Herck, Allan G. Hill, Con Burns, Emanuela Pettenuzzo, Ming-Dong Wang, Stela McLachlan, Ulrike Gehring, Ranko Stevanovic, Nagalla Balakrishna, Lekhraj Rampal, Marjolijn C. E. Bragt, Saeid Eslami, Napoleón Pérez-Farinós, G. K. Mini, Viktoria Anna Kovacs, Rosemarie Martin, Nahla Hwalla, Wei Zheng, Hoang Van Minh, Edward D Janus, Laetitia Huiart, Farhad Pourfarzi, Sudha Ramachandra Rao, Fred Paccaud, Marcia Makdisse, Aye Aye Sein, Enrique Gutiérrez-González, Yang Yang, Anneke Blokstra, Henrike Galenkamp, Jaume Marrugat, Nazan Yardim, Wan Nazaimoon Wan Mohamud, Jesús Ibarluzea, Julio Zuñiga Cisneros, Laura Lauria, Argyro Karakosta, Dragana P Jovic, Jun Hata, Elio Riboli, Piotr Bandosz, Xun Tang, Parvina Mukhtorova, Jean Dallongeville, Jean-Bernard Ruidavets, Anne Tjønneland, Guillermo Frontera, Rahul Malhotra, Thomas Ferrao, Aleksandra Piwońska, Dusan Grafnetter, Mette Rasmussen, Daniel Weghuber, Sherali Rakhmatulloev, Martine Vrijheid, Johann Willeit, Motahareh Kheradmand, Małgorzata Mossakowska, Lechaba Tshepo, Dongfeng Gu, Hyeon Chang Kim, Vilmundur Gudnason, Maria Forsner, Peter Bjerregaard, Leon A. Simons, Rachael McLean, Japhet Killewo, Ramón Suárez-Medina, Y Nikitin, Eng Joo Tan, Jean Claude Mbanya, Aroor Bhagyalaxmi, Renata Kuciene, Kairat Davletov, Jose Eugenio Lozano, Afshin Ostovar, Niloofar Peykari, Guy De Backer, Soheir H Ahmed, Nicholas J. Wareham, Sai Yin Ho, Constanta Huidumac Petrescu, Maria Hassapidou, Iris Pigeot, Myriam Galfo, Susana Cararo Confortin, Blanca Sandra Ruiz-Betancourt, W. M. Monique Verschuren, Catterina Ferreccio, Fabio Galvano, Leila Houti, Daniel Bia, Annika Rosengren, Marcin Rutkowski, Biruta Velika, Joana Araújo, Fernando Rigo, Angela Spinelli, Scott B. McLean, Shirin Djalalinia, Marie Kunešová, Boban Mugoša, Sania Nishtar, Mangesh S. Pednekar, Shahla AlDhukair, Helle-Mai Loit, Antonis Zampelas, Altan Onat, Maciej Banach, Shohreh Naderimagham, Hajer Aounallah-Skhiri, Maja Bæksgaard Jørgensen, Yin Guo, Ewelina Czenczek-Lewandowska, Parasmani Dasgupta, Elvis Oa Wambiya, Inge Huybrechts, Raimund Erbel, Jari Jokelainen, Ana P. Ortiz, Stefan Kiechl, Emmanuel Cohen, Caleb Ochimana, Shynar Abdrakhmanova, Laura Censi, Iqbal Bata, Geetha R Menon, Snehalatha Chamukuttan, Pedro Plans-Rubio, Domenico Palli, Ana Azevedo, Slawomir Koziel, Benoît Salanave, Parinaz Mehdipour, Shu Ti Chiou, Lela Sturua, Lubica Ticha, Felipe Vogt Cureau, Jin Soo Moon, Ming-Hui Zhao, Urho M. Kujala, Nathalie Michels, Ertugrul Celikcan, Jaakko Tuomilehto, Judith Benedics, Tobias F. Rinke de Wit, Agnès Le Port, Reza Homayounfar, Andrea Rodriguez-Martinez, Tai Hing Lam, Yn-Tz Sung, Jürgen König, Kodavanti Mallikharjuna Rao, Hazzaa M. Al-Hazzaa, Karen Morgan, Bogdan Wojtyniak, Cynthia M. Pérez, Ilse Khouw, Manoli Garcia-de-la-Hera, Dong Wook Shin, Genc Burazeri, Ausra Petrauskiene, Charles Sossa Jérome, Kenisha Russell Jonsson, José Boggia, Daniela Galeone, Alice Bonilla-Vargas, Han Cg Kemper, Rahman Shiri, Stefaan Demarest, Else Karin Grøholt, San-Lin You, Adelheid Weber, Juha Auvinen, Aida Pilav, Sibel Gogen, Suzanne N Morin, Wan Mohamad Wan Bebakar, Viviane Cunha Cardoso, Kavumpurathu Raman Thankappan, Hana Zamrazilová, Frank Claessens, Karien Stronks, Helen Gonçalves, Tahir Aris, Luis Revilla, Sérgio Viana Peixoto, Zhamilya Battakova, Jing Liu, Eliza Markidou Ioannidou, Leticia Hernandez Cadena, Priscilla Duboz, Sandjaja, Tiina Laatikainen, Rafel Ramos, Sareh Eghtesad, Judith Simons, Orn Olafsson, E. Shyong Tai, Louise A. Baur, Nihal Thomas, Aung Soe Htet, Bente Sparboe-Nilsen, Paul Elliott, Soon-Woo Park, Angel R. Gonzalez, Ying-Wei Wang, Rob M. van Dam, Ryutaro Ohtsuka, Ludmila Sevcikova, Suhaila Abdul Ghaffar, Lynell V Maniego, Fariborz Mansour-Ghanaei, Maria Dorobantu, Giovanni Viegi, Xiaoguang Yang, Honor Bixby, Prakash C. Gupta, Ofra Kalter-Leibovici, Eugene Sobngwi, Ričardas Radišauskas, Jurate Medzioniene, Roy A Wong-McClure, Kim F. Michaelsen, Antonia Trichopoulou, Tania Tello, Francesco Branca, Johanna Gunnlaugsdottir, Els Clays, Wei-Yen Lim, Suzanne C. Ho, Toomas Veidebaum, Rebecca Goldsmith, Margot González-León, Matthias Nauck, Alibek Mereke, Marta Buoncristiano, Jakob Tarp, Rosalba Rojas-Martínez, Maya Tanrygulyyeva, Reza Malekzadeh, Abdonas Tamosiunas, Dimitrios Poulimeneas, Pedro Ordunez, Isabelle Herter-Aeberli, Khanh Le Nguyen Bao, Anne Juolevi, Vassilis Zafiropulos, Emanuela Gualdi-Russo, Jordi Sunyer, Manu Raj, Chaoqiang Jiang, Sofia Malyutina, Efthymios Kapantais, Maria Lazo-Porras, Maung Maung Than Htike, Michael Hobbs, Ranjit Mohan Anjana, Merike Liivak, Johan G. Eriksson, Margarita Samoutian, Andreia N. Pizarro, Mohammed Rasoul Tarawneh, Jean Woo, Kaspar Staub, Maria Teresa Menzano, Mojtaba Farjam, Adroaldo Cesar Araujo Gaya, Mohammad El-khateeb, Zulfiqar A Bhutta, Mukharram M. Bikbov, Hsien-Ho Lin, Oscar Noboa, Thomas Waldhör, Garry Brian, Simona Costanzo, Frank Tanser, Nor Azwany Yaacob, Michelle Cilia, Ivo Rakovac, Bill Stavreski, Ioannis Pagkalos, Ivan Pećin, Carlo M. Barbagallo, Abla M. Sibai, Yuna He, Matsuda Fumihiko, Bharathi Viswanathan, Ali Reza Safarpour, Wei Cheng Lo, Abdullatif Husseini, Jiang He, Liv Elin Torheim, Nipa Rojroongwasinkul, Aicha Soumare, Astrid Petersmann, Tomasz Grodzicki, Davide Noto, Panayiotis K. Yiallouros, Kelias P. Msyamboza, William R. Tebar, Yingfeng Zheng, Eha Nurk, Bhawesh Koirala, Ana Jelakovic, Suhad Bahijri, Freja B Kampmann, Qi Sheng You, Marika Ferrari, María-Elena González-Villalpando, Aline Wagner, Olfa Saidi, Anwar Batieha, Eduardo Capuano, Coimbatore Subramaniam Shanthirani, Dong Wook Kim, Albina A Fakhretdinova, Tom Wilsgaard, Maria Avdicova, Moesijanti Soekatri, Chiara Donfrancesco, Salim Mohanna, Paola Russo, Uruwan Yamborisut, Rafael dos Santos Henrique, Martin Nankap, Allan Linneberg, Khairil Si-Ramlee, Kirsten Mehlig, Christina Mavrogianni, Raluca Pop, Lèlita Santos, Graziella Bruno, Valentina Peterkova, Iná S. Santos, Georg Lappas, Alberto Palloni, Malay K. Mridha, Andrzej Pajak, Marta García-Solano, Stefaan De Henauw, Daniel Ferrante, Rute Santos, Anders Grøntved, Lucjan Szponar, Mihaela Vladulescu, Chien-An Sun, Jan A. Staessen, Paula Duarte de Oliveira, Norazizah Ibrahim Wong, Maria Nordendahl, Elaine M. Dennison, Jeonghee Lee, Diego Salmerón, Ida Maria Schmidt, Gao Pei, Noushin Mohammadifard, Igor Spiroski, Fernando Rodríguez-Artalejo, Xu Ma, Elin Pettersen Sørgjerd, Valéria Regecová, Cláudia S. Minderico, Johanna A. Otero, Jamila Abubakar Garba, Vesselka Duleva, Rui Ornelas, Ilpo Huhtaniemi, Cesar G. Victora, Lijuan Liu, Rody G. Sy, Mahmood Moosazadeh, Ali Ahmadi, Antonio Pedro Graça, Natalia Nowak-Szczepanska, Miao Li Chee, Michael Sjöström, Charles Agyemang, Shiqi Zhen, Xiu-Hua Guo, Pawel Kurjata, Jardena J. Puder, Mehrdad Azmin, Neil Murphy, Kaosar Afsana, Alireza Sadjadi, Johanna M. Geleijnse, Prashant Mathur, Elysée Claude Bika Lele, Raphael Mendes Ritti-Dias, Yannis Manios, Majid Shirani, Rosemary B. Duda, Liis Nelis, Jurate Klumbiene, Zhengming Chen, Wichai Aekplakorn, Alun Evans, Andrzej Wiecek, Lars Lind, Denise Eldemire-Shearer, Bernardo L. Horta, Macia Enguerran, Seyed Rasoul Zakavi, Daniel Fernández-Bergés, Kumiko Ohara, Ursula Kiechl-Kohlendorfer, Hermann Brenner, Przemyslaw Slusarczyk, Espen Bjertness, Jutta Stieber, Augusto Di Castelnuovo, Joel G. R. Roy, Aryeh D. Stein, Ruth Frikke-Schmidt, Vera Musil, Amaneh Shayanrad, Marcel Goldberg, Ramon O. Jimenez, Mohammad Reza Fattahi, Jolanda Hyska, Amir Houshang Mehrparvar, Elin Kolle, Mohamed Bamoshmoosh, Michelle Holdsworth, Felipe F. Casanueva, Børge G. Nordestgaard, Niels Wedderkopp, Eva Corpeleijn, Elias F. Gudmundsson, Antonio Mistretta, Daniel Lemogoum, Larissa Pruner Marques, Slavica Sović, Olli T. Raitakari, Marco Aurélio Peres, Alexandra Cucu, Gregorio Varela-Moreiras, Janine Clarke, Andrea Gazzinelli, Mieczysław Litwin, Sara Schramm, Xenophon Theodoridis, Harshpal Singh Sachdev, Mohammad Reza Mirjalili, Dimitrios Papandreou, Peter T. Katzmarzyk, Benjamin Acosta-Cazares, Ben Schöttker, Prabhdeep Kaur, Norlaila Mustafa, Shariq Rashid Masoodi, Sadaf G. 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Duante, Sheikh Mohammed Shariful Islam, Quang Ngoc La, Ricky Eddie, Petra Rust, Daniela Rodrigues, Dirk De Bacquer, Karen Sparrenberger, Agneta Sjöberg, Thet Thet Mu, Katarzyna Dereń, Cora L. Craig, Jorge Motta, Janina Petkeviciene, Boyd Swinburn, Paibul Suriyawongpaisal, Visnja Djordjic, Ramón Alberto Rascón-Pacheco, Pradeep Joshi, Daan Kromhout, Marius B. Bjertness, Stefano Marventano, Juel Jarani, Alireza Khosravi, Eva Martos, David De Ridder, Lizzy M. Brewster, Nico Dragano, Liam Smeeth, Kenji Shibuya, Emma Ruiz Moreno, Hashem Jaddou, Grzegorz Sobek, Dimitrios Trichopoulos, Marvin Cervantes-Loaiza, Abu Am Hanif, Elaine M. Murtagh, Carlos A. Aguilar-Salinas, Graziella D'Arrigo, Kyungwon Oh, Heiner Boeing, Regina Heidinger-Felso, André Luiz Sena Guimarães, Balkish M. Naidu, Avula Laxmaiah, Ana M. B. Menezes, Marie Eliasen, Francesco Pistelli, Yuan He, Dusko Bjelica, José A. 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Machado-Rodrigues, Fatemeh Malekzadeh, Shouling Wu, Jennifer L. Baker, Clicerio González-Villalpando, Eleonora d'Orsi, Irene G. M. van Valkengoed, Anna Fijałkowska, Wen-Harn Pan, Gregor Starc, Meghnath Dhimal, Murat Topbaş, George Moschonis, Robert Eggertsen, Abdullah Alkandari, Quang Ngoc Nguyen, Janette Walton, Elnaz Faramarzi, Saeed Dastgiri, Lien Braeckevelt, Nasheeta Peer, Radka Taxová Braunerová, Mohamed M. Ali, Steiner Krokstad, Harald Geiger, Morteza Shamshirgaran, Lela Shengelia, María Ángeles Dal Re Saavedra, Silvana Donoso, Khem Bahadur Karki, Timothy J. Key, Maria G. Grammatikopoulou, Susana Vale, Felix K. Assah, Juan A Rivera, Peter H. Whincup, Oana-Florentina Gheorghe-Fronea, Cassiano Ricardo Rech, Paul Ferdinand M. Reganit, Rachakulla Hari Kumar, Jaakko Mursu, Luis A. Moreno, Glen Gironella, Jelena Kos, Tilema Cama, Haakon E. Meyer, Jun Ma, Raphael E. Arku, Ziad Abdeen, Dianna J. Magliano, Jitendra Jonnagaddala, Konstantinos Gkiouras, Paola Nardone, Alberto Barceló, Tomi-Pekka Tuomainen, Francesco Gianfagna, Stefania Maggi, Mohammad Hossein Somi, Behrooz Hamzeh, Miquel Porta, Vesna Jureša, Alexander D. Deev, David Faeh, Antonio Bernabe-Ortiz, Sirkka Keinänen-Kiukaanniemi, Ian Hambleton, Stefan Savin, Andre Pascal Kengne, R. Krishna Kumar, Kurt Widhalm, Marco M Ferrario, Parisa Amiri, Anjani Kumar Jha, Thamara Hubler Figueiró, Jana Kratenova, Claudia M. Hormiga, Maria Tsigga, Zivka Dika, Indrapal I. Meshram, Ei Ei K. Nang, Ian Rouse, Rusidah Selamat, Paul Korrovits, Grethe S. Tell, Julie Taylor, Anabela Mota-Pinto, Paolo Vineis, Kotsedi D Monyeki, Khuong Quynh Long, Frank J Rühli, Shelly R. McFarlane, Sara Santos Sanz, Edyta Łuszczki, Maria G. Stathopoulou, Tara Coppinger, Karin De Ridder, Lucie Viet, Anna Bugge, Mehdi Yaseri, Safiah Md Yusof, Sandra C. Fuchs, Muhammad Islam, Irfan Nuhoglu, Rui Providência, Bernard Maire, Leandra Abarca-Gómez, Sinead Brophy, Maria Ruiz-Castell, Daniela Pierannunzio, Cristina Taddei, Gowri Mahasampath, Gustavo Velasquez-Melendez, Hanna Tolonen, Sudhir Kowlessur, Bagher Larijani, Laura Torres-Collado, Susi Kriemler, Ali Akbar Shayesteh, Cynthia Robitaille, Jorge Escobedo-de la Peña, Yufang Bi, Chinh Nguyen Huu, Line Tang Møllehave, Vincent Jr DeGennaro, Noor Ani Ahmad, Anar Dushpanova, Agustinus Soemantri, Susana Sans, Ionela Pascanu, Gwenaëlle Le Coroller, Inger Ariansen, Kodanda R Kanala, Gert B. M. Mensink, Abhijit Sen, Sergej M. Ostojic, Hanan F. Abdul Rahim, Hélène Delisle, Francisco J. Félix-Redondo, Yadlapalli S. Kusuma, Michael Knoflach, Moein Yoosefi, Tanja G. M. Vrijkotte, Wolfgang Ahrens, Osvaldo Santos, Bethlehem D. Solomon, Erik Lykke Mortensen, Nikhil D. 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Chan School of Public Health, Middlesex University [London], Organisation Mondiale de la Santé / World Health Organization Office (OMS / WHO), Montpellier Interdisciplinary center on Sustainable Agri-food systems (Social and nutritional sciences) (UMR MoISA), Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad)-Institut de Recherche pour le Développement (IRD)-Centre International de Hautes Etudes Agronomiques Méditerranéennes - Institut Agronomique Méditerranéen de Montpellier (CIHEAM-IAMM), Centre International de Hautes Études Agronomiques Méditerranéennes (CIHEAM)-Centre International de Hautes Études Agronomiques Méditerranéennes (CIHEAM)-Institut national d’études supérieures agronomiques de Montpellier (Montpellier SupAgro), Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Bordeaux population health (BPH), Université de Bordeaux (UB)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM), Interactions Gène-Environnement en Physiopathologie Cardio-Vasculaire (IGE-PCV), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Wellcome TrustEuropean Commission, Clinical Developmental Psychology, APH - Mental Health, Sociology, The Social Context of Aging (SoCA), Nutrition and Health, Iurilli, Maria LC [0000-0003-0409-1635], Zhou, Bin [0000-0002-1741-8628], Ezzati, Majid [0000-0002-2109-8081], Apollo - University of Cambridge Repository, Epidemiology and Data Science, APH - Aging & Later Life, APH - Societal Participation & Health, Public and occupational health, APH - Health Behaviors & Chronic Diseases, VU University medical center, APH 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Medical Research Center, Luxembourg Institute of Health, Bispebjerg and Frederiksberg Hospital, Barcelona Institute for Global Health CIBERESP, World Health Organization Regional Office for the Eastern Mediterranean, Bombay Hospital and Medical Research Centre, Research Center for Social Determinants of Health, UMR CNRS-MNHN 7206 Eco-anthropologie, University of Lille, Lille University Hospital, Western Norway University of Applied Sciences, Norwegian School of Sport Sciences, Madras Diabetes Research Foundation, Zahedan University of Medical Sciences, National Institute of Public Health, Institute of Public Health of the University of Porto, Norwegian Institute of Public Health, University of Massachusetts Amherst, Abt Associates, University of Iceland, University of Yaoundé1, Federal University of Pelotas, University of Medicine 1, Oulu University Hospital, Banska Bystrica Regional Authority of Public Health, Tel- Aviv University, Hebrew University of Jerusalem, University of Porto 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Huiart , Constanta Huidumac Petrescu , Martijn Huisman , Abdullatif Husseini , Chinh Nguyen Huu , Inge Huybrechts , Nahla Hwalla , Jolanda Hyska , Licia Iacoviello , Jesús M Ibarluzea , Mohsen M Ibrahim , Norazizah Ibrahim Wong , M Arfan Ikram , Violeta Iotova , Vilma E Irazola , Takafumi Ishida , Muhammad Islam , Sheikh Mohammed Shariful Islam , Masanori Iwasaki , Jeremy M Jacobs , Hashem Y Jaddou , Tazeen Jafar , Kenneth James , Kazi M Jamil , Konrad Jamrozik , Imre Janszky , Edward Janus , Juel Jarani , Marjo-Riitta Jarvelin , Grazyna Jasienska , Ana Jelakovic , Bojan Jelakovic , Garry Jennings , Anjani Kumar Jha , Chao Qiang Jiang , Ramon O Jimenez , Karl-Heinz Jöckel , Michel Joffres , Mattias Johansson , Jari J Jokelainen , Jost B Jonas , Jitendra Jonnagaddala , Torben Jørgensen , Pradeep Joshi , Farahnaz Joukar , Dragana P Jovic , Jacek J Jóźwiak , Anne Juolevi , Gregor Jurak , Iulia Jurca Simina , Vesna Juresa , Rudolf Kaaks , Felix O Kaducu , Anthony Kafatos , Eero O Kajantie , Zhanna Kalmatayeva , Ofra Kalter-Leibovici , Yves Kameli , Freja B Kampmann , Kodanda R Kanala , Srinivasan Kannan , Efthymios Kapantais , Argyro Karakosta , Line L Kårhus , Khem B Karki , Marzieh Katibeh , Joanne Katz , Peter T Katzmarzyk , Jussi Kauhanen , Prabhdeep Kaur , Maryam Kavousi , Gyulli M Kazakbaeva , Ulrich Keil , Lital Keinan Boker , Sirkka Keinänen-Kiukaanniemi , Roya Kelishadi , Cecily Kelleher , Han Cg Kemper , Andre P Kengne , Maryam Keramati , Alina Kerimkulova , Mathilde Kersting , Timothy Key , Yousef Saleh Khader , Davood Khalili , Kay-Tee Khaw , Bahareh Kheiri , Motahareh Kheradmand , Alireza Khosravi , Ilse Msl Khouw , Ursula Kiechl-Kohlendorfer , Stefan Kiechl , Japhet Killewo , Dong Wook Kim , Hyeon Chang Kim , Jeongseon Kim , Jenny M Kindblom , Heidi Klakk , Magdalena Klimek , Jeannette Klimont , Jurate Klumbiene , Michael Knoflach , Bhawesh Koirala , Elin Kolle , Patrick Kolsteren , Jürgen König , Raija Korpelainen , Paul Korrovits , Magdalena Korzycka , Jelena Kos , Seppo Koskinen , Katsuyasu Kouda , Viktoria A Kovacs , Sudhir Kowlessur , Slawomir Koziel , Jana Kratenova , Wolfgang Kratzer , Susi Kriemler , Peter Lund Kristensen , Steinar Krokstad , Daan Kromhout , Herculina S Kruger , Ruzena Kubinova , Renata Kuciene , Urho M Kujala , Enisa Kujundzic , Zbigniew Kulaga , R Krishna Kumar , Marie Kunešová , Pawel Kurjata , Yadlapalli S Kusuma , Kari Kuulasmaa , Catherine Kyobutungi , Quang Ngoc La , Fatima Zahra Laamiri , Tiina Laatikainen , Carl Lachat , Youcef Laid , Tai Hing Lam , Christina-Paulina Lambrinou , Edwige Landais , Vera Lanska , Georg Lappas , Bagher Larijani , Tint Swe Latt , Laura Lauria , Maria Lazo-Porras , Gwenaëlle Le Coroller , Khanh Le Nguyen Bao , Agnès Le Port , Tuyen D Le , Jeannette Lee , Jeonghee Lee , Paul H Lee , Nils Lehmann , Terho Lehtimäki , Daniel Lemogoum , Naomi S Levitt , Yanping Li , Merike Liivak , Christa L Lilly , Wei-Yen Lim , M Fernanda Lima-Costa , Hsien-Ho Lin , Xu Lin , Yi-Ting Lin , Lars Lind , Allan Linneberg , Lauren Lissner , Mieczyslaw Litwin , Lijuan Liu , Wei-Cheng Lo , Helle-Mai Loit , Khuong Quynh Long , Luis Lopes , Oscar Lopes , Esther Lopez-Garcia , Tania Lopez , Paulo A Lotufo , José Eugenio Lozano , Janice L Lukrafka , Dalia Luksiene , Annamari Lundqvist , Robert Lundqvist , Nuno Lunet , Charles Lunogelo , Michala Lustigová , Edyta Łuszczki , Guansheng Ma , Jun Ma , Xu Ma , George Ll Machado-Coelho , Aristides M Machado-Rodrigues , Luisa M Macieira , Ahmed A Madar , Stefania Maggi , Dianna J Magliano , Sara Magnacca , Emmanuella Magriplis , Gowri Mahasampath , Bernard Maire , Marjeta Majer , Marcia Makdisse , Päivi Mäki , Fatemeh Malekzadeh , Reza Malekzadeh , Rahul Malhotra , Kodavanti Mallikharjuna Rao , Sofia K Malyutina , Lynell V Maniego , Yannis Manios , Jim I Mann , Fariborz Mansour-Ghanaei , Enzo Manzato , Paula Margozzini , Anastasia Markaki , Oonagh Markey , Eliza Markidou Ioannidou , Pedro Marques-Vidal , Larissa Pruner Marques , Jaume Marrugat , Yves Martin-Prevel , Rosemarie Martin , Reynaldo Martorell , Eva Martos , Katharina Maruszczak , Stefano Marventano , Luis P Mascarenhas , Shariq R Masoodi , Ellisiv B Mathiesen , Prashant Mathur , Alicia Matijasevich , Tandi E Matsha , Christina Mavrogianni , Artur Mazur , Jean Claude N Mbanya , Shelly R McFarlane , Stephen T McGarvey , Martin McKee , Stela McLachlan , Rachael M McLean , Scott B McLean , Breige A McNulty , Sounnia Mediene Benchekor , Jurate Medzioniene , Parinaz Mehdipour , Kirsten Mehlig , Amir Houshang Mehrparvar , Aline Meirhaeghe , Jørgen Meisfjord , Christa Meisinger , Ana Maria B Menezes , Geetha R Menon , Gert Bm Mensink , Maria Teresa Menzano , Alibek Mereke , Indrapal I Meshram , Andres Metspalu , Haakon E Meyer , Jie Mi , Kim F Michaelsen , Nathalie Michels , Kairit Mikkel , Karolina Milkowska , Jody C Miller , Cláudia S Minderico , G K Mini , Juan Francisco Miquel , Mohammad Reza Mirjalili , Daphne Mirkopoulou , Erkin Mirrakhimov , Marjeta Mišigoj-Durakovic , Antonio Mistretta , Veronica Mocanu , Pietro A Modesti , Sahar Saeedi Moghaddam , Bahram Mohajer , Mostafa K Mohamed , Shukri F Mohamed , Kazem Mohammad , Zahra Mohammadi , Noushin Mohammadifard , Reza Mohammadpourhodki , Viswanathan Mohan , Salim Mohanna , Muhammad Fadhli Mohd Yusoff , Iraj Mohebbi , Farnam Mohebi , Marie Moitry , Drude Molbo , Line T Møllehave , Niels C Møller , Dénes Molnár , Amirabbas Momenan , Charles K Mondo , Michele Monroy-Valle , Eric Monterrubio-Flores , Kotsedi Daniel K Monyeki , Jin Soo Moon , Mahmood Moosazadeh , Leila B Moreira , Alain Morejon , Luis A Moreno , Karen Morgan , Suzanne N Morin , Erik Lykke Mortensen , George Moschonis , Malgorzata Mossakowska , Aya Mostafa , Anabela Mota-Pinto , Jorge Mota , Mohammad Esmaeel Motlagh , Jorge Motta , Marcos André Moura-Dos-Santos , Malay K Mridha , Kelias P Msyamboza , Thet Thet Mu , Magdalena Muc , Boban Mugoša , Maria L Muiesan , Parvina Mukhtorova , Martina Müller-Nurasyid , Neil Murphy , Jaakko Mursu , Elaine M Murtagh , Kamarul Imran Musa , Sanja Music Milanovic , Vera Musil , Norlaila Mustafa , Iraj Nabipour , Shohreh Naderimagham , Gabriele Nagel , Balkish M Naidu , Farid Najafi , Harunobu Nakamura , Jana Námešná , Ei Ei K Nang , Vinay B Nangia , Martin Nankap , Sameer Narake , Paola Nardone , Matthias Nauck , William A Neal , Azim Nejatizadeh , Chandini Nekkantti , Keiu Nelis , Liis Nelis , Ilona Nenko , Martin Neovius , Flavio Nervi , Chung T Nguyen , Nguyen D Nguyen , Quang Ngoc Nguyen , Ramfis E Nieto-Martínez , Yury P Nikitin , Guang Ning , Toshiharu Ninomiya , Sania Nishtar , Marianna Noale , Oscar A Noboa , Helena Nogueira , Teresa Norat , Maria Nordendahl , Børge G Nordestgaard , Davide Noto , Natalia Nowak-Szczepanska , Mohannad Al Nsour , Irfan Nuhoglu , Eha Nurk , Terence W O'Neill , Dermot O'Reilly , Galina Obreja , Caleb Ochimana , Angélica M Ochoa-Avilés , Eiji Oda , Kyungwon Oh , Kumiko Ohara , Claes Ohlsson , Ryutaro Ohtsuka , Örn Olafsson , Maria 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Versailles Saint-Quentin-en-Yvelines (UVSQ)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay-Université Paris Cité (UPCité), Université Paris Cité (UPCité), Centre International de Hautes Études Agronomiques Méditerranéennes (CIHEAM)-Centre International de Hautes Études Agronomiques Méditerranéennes (CIHEAM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Institut Agro - Montpellier SupAgro, and Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)

Subjects
Population -- Health aspects, Leanness, Baixo peso/Underweight, none, Double burden, alipainoisuus, tulotaso, global health, systematic analysis, Sedentary behaviors, RC1200, Prospective associations, 0302 clinical medicine, underweight, nälänhätä, Biology (General), skin and connective tissue diseases, Children, ComputingMilieux_MISCELLANEOUS, Body mass index, Human Nutrition & Health, education.field_of_study, Humane Voeding & Gezondheid, ylipaino, General Medicine, kansainvälinen vertailu, 3. Good health, World health, Medicine, A100 Pre-clinical Medicine, Population distribution, medicine.medical_specialty, QH301-705.5, Science, Socio-culturale, Nursing, Social sciences, General Biochemistry, Genetics and Molecular Biology, 03 medical and health sciences, Thinness, SDG 3 - Good Health and Well-being, BMI, epidemiology, obesity, None, Humans, Obesidade/Obesity, SDG 2 - Zero Hunger, education, VLAG, US adults, Omvårdnad, body mass index, malnutrition, obesity, underweight, nutritional and metabolic diseases, medicine.disease, terveellisyys, Obesity, Faculdade de Ciências Sociais, Body Mass Index, Prevalence, Risk Factors, General Biochemistry, WIAS, lihavuus, RA, Demography, N.A, double burden, Settore MED/09 - Medicina Interna, alueelliset erot, Nutrition and Disease, Animal Nutrition, [SDV]Life Sciences [q-bio], Medizin, 030204 cardiovascular system & hematology, 0601 Biochemistry and Cell Biology, Change distribution of body mass index, RA0421, Voeding en Ziekte, Epidemiology, Medicine and Health Sciences, Global health, Índice de massa corporal/Body Mass Index, 030212 general & internal medicine, Underweight, painoindeksi, 2. Zero hunger, General Neuroscience, aliravitsemus, elintarvikkeet, health, Public Health, Global Health, Social Medicine and Epidemiology, Diervoeding, 3142 Public health care science, environmental and occupational health, purl.org/pe-repo/ocde/ford#3.01.03 [https], Chinese adults, pooled analysis, medicine.symptom, Diet quality, B120 Physiology, Research Article, trends, purl.org/pe-repo/ocde/ford#1.06.03 [https], prevalence, Population, Mothers, Genetics and Molecular Biology, 3121 Internal medicine, medicine, Life Science, ddc:610, 3125 Otorhinolaryngology, ophthalmology, kehonkoostumus, Nutrition, Australian adults, General Immunology and Microbiology, purl.org/pe-repo/ocde/ford#3.01.04 [https], Ciências sociais, Folkhälsovetenskap, global hälsa, socialmedicin och epidemiologi, Malnutrition, Epidemiology and Global Health, sense organs, Estilos de Vida e Impacto na Saúde
Abstract

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., Wellcome Trust, Medical Research Council, peer-reviewed

Published
2021

185. Author response: Heterogeneous contributions of change in population distribution of body mass index to change in obesity and underweight

Author

Zahra Mohammadi, Abdul Basit, Helena I. S. Nogueira, Soile E. Puhakka, Hongsheng Bi, Ari Voutilainen, Davood Khalili, Bin Zhou, Dermot O'Reilly, Natascia Rinaldo, Paulo A. Lotufo, Bahareh Kheiri, Thein Thein Htay, Simona Giampaoli, Goodarz Danaei, M. Fernanda Lima-Costa, Simona Bo, Peter Schnohr, Jerzy Chudek, Francesco Panza, Ling Yang, Katia Vergetti Bloch, Vincenzo Capuano, Holly E. Syddall, Dong Zhao, Indah Suci Widyahening, Maria Lorenza Muiesan, Leng Huat Foo, Mohsen Azimi-Nezhad, Merete Osler, Laura Torres-Collado, Manu Raj, Adroaldo Cesar Araujo Gaya, Susi Kriemler, Ali Akbar Shayesteh, Aneta Grajda, Anette Varbo, Kazem Mohammad, Leila Beltrami Moreira, Shu Ti Chiou, Iuliia A Rusakova, Jyh Eiin Wong, Torben Jørgensen, Lela Sturua, Lubica Ticha, Hamid Hakimi, Hazzaa M. Al-Hazzaa, Yanina Zócalo, Freda Pitakaka, Savvas C. Savva, Rajeev Gupta, Jennifer Servais, Marie Kunešová, Johanna M. Geleijnse, Elysée Claude Bika Lele, Yannis Manios, Jorge Escobedo-de la Peña, Yufang Bi, Chinh Nguyen Huu, Sibel Gogen, Viviane Cunha Cardoso, Kristine H. Allin, Ana Azevedo, Line Tang Møllehave, Vincent Jr DeGennaro, Novie O. Younger-Coleman, Gretchen A Stevens, Dickman Gareta, Holger Theobald, Anja Schienkiewitz, Bekbolat Zholdin, Janice Luisa Lukrafka, Adela Chirita-Emandi, Ulla Roggenbuck, Kenisha Russell Jonsson, Robespierre Ribeiro, Gabriele Eiben, Eero Kajantie, Sounnia Mediene Benchekor, Fariborz Mansour-Ghanaei, Mary Simon, Prakash C. Gupta, Mohammad Esmaeel Motlagh, Emanuela Gualdi-Russo, María Elena Díaz-Sánchez, Pilar Guallar-Castillón, Bee Koon Poh, Cristina Padez, Azaliia M Tuliakova, Sarah P. Garnett, William R. Tebar, Yingfeng Zheng, Suhad Bahijri, Christina Mavrogianni, Mihaela Vladulescu, Jan A. Staessen, Paula Duarte de Oliveira, Rui Ornelas, Michael Sjöström, Charles Agyemang, Slawomir Koziel, Shohreh Naderimagham, Jari Jokelainen, Stephen T. 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Stathopoulou, Alibek Mereke, Mari-Liis Tammesoo, Axel C. Carlsson, Helen Gonçalves, Idowu O Senbanjo, Jim Mann, Rajendra Pradeepa, Juel Jarani, Eva Martos, Eugene Sobngwi, Themistoklis Tzotzas, Vassilis Zafiropulos, Reina Engle-Stone, Atul Trivedi, Hui Cai, Sarah Filippi, Georg Posch, Galina Obreja, Cecily Kelleher, Sareh Eghtesad, Chung T Nguyen, Kay-Tee Khaw, Joseph Cacciottolo, Ana Henriques, Yi-Ting Lin, Anil Poudyal, Liam Smeeth, Kenji Shibuya, Emma Ruiz Moreno, Annamari Lundqvist, Thor Aspelund, Caroline H.D. Fall, Philippe Amouyel, Kristyna Zejglicova, Argyro Karakosta, Piotr Bandosz, Juvenal Soares Dias-da-Costa, Maria Lazo-Porras, Maung Maung Than Htike, Dalia Luksiene, Jutta Stieber, Augusto Di Castelnuovo, Aryeh D. Stein, Lechaba Tshepo, Judith Benedics, Aletta E. Schutte, Jürgen König, Magdalena Korzycka, Grzegorz Sobek, Dimitrios Trichopoulos, Tai Hing Lam, Yn-Tz Sung, Masanori Iwasaki, Elias F. Gudmundsson, Antonio Mistretta, Daniel Lemogoum, Nimmathota Arlappa, Isabelle Herter-Aeberli, Khanh Le Nguyen Bao, Shoichiro Tsugane, Kaosar Afsana, Alireza Sadjadi, Myriam Galfo, Jean Claude Mbanya, Bernardo L. Horta, Marleen E. Hendriks, M. Arfan Ikram, Fadia AlBuhairan, Huashuai Chen, Marzieh Katibeh, Sidsel Graff-Iversen, Sahar Saeedi Moghaddam, Larissa Pruner Marques, Louise Eriksen, Aleksandra Gomula, Ricky Eddie, Maciej Banach, Jost B. Jonas, Andrea R. V. R. Horimoto, Slavica Sović, Charles Mondo, Felix Gutzwiller, Mariana Sbaraini, Aye Aye Sein, Henrike Galenkamp, Jaume Marrugat, Nazan Yardim, Cecilia Björkelund, Luigi Palmieri, Roya Kelishadi, Jie Mi, Nahla Hwalla, Jing Liu, Davide Noto, Panayiotis K. Yiallouros, Kelias P. Msyamboza, Judith Simons, Sofia Malyutina, Michele Monroy-Valle, Andres Metspalu, Lariane M Ono, Rafaela Rosário, Flora A. Ukoli, Efthymios Kapantais, Enzo Manzato, S. Goya Wannamethee, Alison J Price, Gregorio Varela-Moreiras, Ali Reza Safarpour, Erfan Ghasemi, Janine Clarke, René Charles Sylva, Wan Nazaimoon Wan Mohamud, Zhamyila Usupova, Chaoqiang Jiang, Julio Zuñiga Cisneros, Freja B Kampmann, Wei Cheng Lo, Reza Mohammadpourhodki, Kaspar Staub, Mojtaba Farjam, Vincenzo Solfrizzi, Garry L. Jennings, Fabio Galvano, Monika Zuziak, Karin De Ridder, Lucie Viet, Anna Bugge, Mehdi Yaseri, Safiah Md Yusof, Sandra C. Fuchs, Emmanuel Cohen, Snehalatha Chamukuttan, Maria Ruiz-Castell, Karen Sparrenberger, Pedro Plans-Rubio, Wei Zheng, Eldridge Ferrer, Martijn Huisman, Maria Hassapidou, Iris Pigeot, Jakub Stokwiszewski, Domenico Palli, Ewelina Czenczek-Lewandowska, Ramiro Guerrero, Farzad Hadaegh, Han Cg Kemper, Saeid Safiri, Ivan Pećin, Arnaud Chiolero, Niels Møller, Jorge Bezerra, Ulrike Gehring, Iná S. Santos, Dénes Molnár, Muhammad Fadhli Mohd Yusoff, Marie Moitry, Nizal Sarrafzadegan, Jacqueline F. Price, Ranko Stevanovic, Sai Yin Ho, Georg Lappas, Alberto Palloni, Malay K. Mridha, Elaine M. Dennison, Jeonghee Lee, Saeid Eslami, Rahman Shiri, Japhet Killewo, Juergen Breckenkamp, Mathilde Kersting, Y Nikitin, Iqbal Bata, Geetha R Menon, Maria Avdicova, Sanjay Rampal, Antônio Augusto Moura da Silva, Kirsten Mehlig, Chien-An Sun, Ramin Heshmat, Violeta Iotova, Stefaan Demarest, Mette Rasmussen, Dirk De Bacquer, San-Lin You, Suzanne N Morin, Martin Gulliford, Maties Torrent, Luc Dauchet, Fred Paccaud, Paibul Suriyawongpaisal, Sherali Rakhmatulloev, Hyeon Chang Kim, Markku Peltonen, Ruth Frikke-Schmidt, Vera Musil, Ahmad Ali Zainuddin, Angela Chetrit, Dan Zhu, Gowri Mahasampath, Ulrich Keil, Sérgio Viana Peixoto, Haiquan Xu, Helle-Mai Loit, Valérie Deschamps, Ilpo Huhtaniemi, Lijuan Liu, Marialaura Bonaccio, Altan Onat, Rody G. Sy, José María Huerta, Ko Ko Zaw, Akihiro Yoshihara, Peter Ueda, Belgin Ünal, Rachel Dankner, Andrzej Wiecek, Eman Aly, Ruzena Kubinova, Justina Vaitkeviciute, Hanna Tolonen, Priscilla Duboz, Orn Olafsson, Yin Guo, Chiara Donfrancesco, Salim Mohanna, Dusan Grafnetter, Daniel Weghuber, Ali Ahmadi, Rosemary B. Duda, E. Shyong Tai, Louise A. Baur, Nihal Thomas, Prabhdeep Kaur, Norlaila Mustafa, Shariq Rashid Masoodi, Liis Nelis, Badreya Al-Lahou, J. Jaime Miranda, Lèlita Santos, Aroor Bhagyalaxmi, Mohamed Bamoshmoosh, Børge G. Nordestgaard, Jeannette Lee, Ahmad Reza Dorosty, Alain Morejon, Ying-Wei Wang, Jakob Tarp, Rosalba Rojas-Martínez, Luxia Zhang, Bahram Mohajer, Maja Bæksgaard Jørgensen, Jurate Klumbiene, Zhengming Chen, Ambady Ramachandran, Andrea Rodriguez-Martinez, Alisha N. Wade, Suyeon Park, Janne Schurmann Tolstrup, Lucjan Szponar, Krishna Kumar Aryal, Tahir Aris, Mahfuzar Rahman, Dorja Vočanec, Juan P. González-Rivas, Rob M. van Dam, Daniel Bia, Oonagh Markey, Ryutaro Ohtsuka, Kumiko Ohara, Ričardas Radišauskas, Jurate Medzioniene, Tiina Vlasoff, Tania Tello, Suzanne C. Ho, Kodavanti Mallikharjuna Rao, May Soe Aung, Vesselka Duleva, Michael Hobbs, Lutgarde Thijs, Marjolein Visser, Parasmani Dasgupta, Inge Huybrechts, Raimund Erbel, Alice Bonilla-Vargas, Hermann Brenner, Mohammad Reza Fattahi, Jolanda Hyska, Roman Topor-Madry, Ranjit Mohan Anjana, Merike Liivak, Eruke E. Egbagbe, Mathilde Savy, Herculina S. Kruger, Neil Murphy, Vinay Nangia, Cesar G. Victora, Mostafa K. Mohamed, H. Bas Bueno-de-Mesquita, Gabriella Gruden, Marcos André Moura-dos-Santos, Mohammed Rasoul Tarawneh, Maria Teresa Menzano, Francesco Branca, Abdonas Tamosiunas, Elena Bogova, Niveen M E Abu-Rmeileh, Maroje Sorić, Aleksander Giwercman, Elżbieta Dziankowska-Zaborszczyk, Tatjana Hejgaard, Yves Kameli, Margarita Samoutian, Andreia N. Pizarro, Jin Soo Moon, Frank Claessens, Zulfiqar A Bhutta, Frank Tanser, Nor Azwany Yaacob, Vanina Bongard, Gregor Jurak, Johan G. Eriksson, Christina-Paulina Lambrinou, Hanspeter Stamm, Kim Overvad, Yanping Li, Carsten Oliver Schmidt, Thomas Meinertz Dantoft, Wichai Aekplakorn, Anwar Batieha, Eduardo Capuano, Teresa Haugsgjerd, Jeremy M. Jacobs, Paola Russo, Nguyen D Nguyen, Luis Revilla, Hossein Poustchi, Farid Najafi, Giovanni de Gaetano, Wan Mohamad Wan Bebakar, Paul Elliott, Denise Eldemire-Shearer, Angela Döring, Giovanni Viegi, Xiaoguang Yang, María-Elena González-Villalpando, Maria Puiu, Maria Benedetta Donati, Andrew Wong, Tomasz Zdrojewski, Carlos P. Boissonnet, Mohamad Hasnan Ahmad, Mahmudur Rahman, Günther Fink, Marcia Makdisse, Dragana P Jovic, Aline Wagner, Coimbatore Subramaniam Shanthirani, Pascal Bovet, Dong Wook Kim, Tom Wilsgaard, Anders Grøntved, Thirunavukkarasu Sathish, Antonia Trichopoulou, Noushin Mohammadifard, Igor Spiroski, Natasja M. van Schoor, Cláudia S. Minderico, Betina H. Thuesen, Queenie Chan, Ulf Ekelund, Laura A. Rodríguez-Villamizar, Line Lund Kårhus, Cihangir Erem, Amina Barkat, Maria Paula Santos, Fernanda Cunha Soares, Constanta Huidumac Petrescu, Allan G. Hill, Honor Bixby, Benoît Salanave, Joana Carvalho, Maigeng Zhou, Ofra Kalter-Leibovici, Roy A Wong-McClure, Kim F. Michaelsen, Doris Stöckl, Rosalynn Siantar, Jouko Saramies, José R. Banegas, Quang Ngoc La, Uruwan Yamborisut, Parinaz Mehdipour, Farhad Pourfarzi, Sudha Ramachandra Rao, Katsuyasu Kouda, Chien-Jen Chen, Rafael dos Santos Henrique, Martin Nankap, Allan Linneberg, Ronald D. Gregor, Rudolf Kaaks, Maria do Carmo Franco, Marta García-Solano, Beata Gurzkowska, Bahman Cheraghian, Stefaan De Henauw, Daniel Ferrante, Johanna A. Otero, Jamila Abubakar Garba, Antonio Pedro Graça, Sumit Bharadwaj, Shiqi Zhen, Xiu-Hua Guo, Prashant Mathur, Raphael Mendes Ritti-Dias, Kouamelan Doua, Esteban Carmuega, Majid Shirani, Przemyslaw Slusarczyk, Petra Rust, Visnja Djordjic, Farahnaz Joukar, Johanna Gunnlaugsdottir, Leila Houti, Nayu Ikeda, Imperia Brajkovich, Amirabbas Momenan, Erik J. Timmermans, Marcin Rutkowski, Biruta Velika, Joana Araújo, Jostein Steene-Johannessen, Christa L. Lilly, Per Tynelius, Michael Tornaritis, Anne Juolevi, Fatima Zahra Laamiri, Carl Lachat, Kai-Uwe Saum, Espen Bjertness, Ana P. Ortiz, Joel G. R. Roy, Himanshu K. Chaturvedi, Michelle Holdsworth, Niels Wedderkopp, Johan Van der Heyden, Mukharram M. Bikbov, Hsien-Ho Lin, Eva Corpeleijn, Harshpal Singh Sachdev, Mohammad Reza Mirjalili, Maria del Cristo Rodriguez-Perez, Michala Lustigová, Tuyen D Le, Teresa Norat, Hana Zamrazilová, Garry Brian, Tien Yin Wong, Rosa Haghshenas, Clive Osmond, Diego Giulliano Destro Christofaro, Mahmood Moosazadeh, Vilma Irazola, Olli T. Raitakari, Marco Aurélio Peres, Terho Lehtimäki, Shuohua Chen, Dimitrios Papandreou, Robert J. Adams, Sigmund A. Anderssen, Peter T. Katzmarzyk, Luisa M Macieira, Félicité Tchibindat, Lital Keinan Boker, Toshiharu Ninomiya, Morten Sodemann, Jytte Halkjær, Zbigniew Kułaga, Sophie Visvikis-Siest, Farshad Farzadfar, N Capkova, Zumin Shi, Maria Turley, Zbigniew Gaciong, Giovanni Veronesi, Martin McKee, Veikko Salomaa, Gilad Twig, Elisabetta L. Romeo, Peter Kristensen, Grazyna Jasienska, Victor Guillermo Sequera, Mario V. Capanzana, Con Burns, Emanuela Pettenuzzo, Ming-Dong Wang, Jonathan Giovannelli, Stela McLachlan, Ellis Owusu-Dabo, Stefania Toselli, Maria Teresa Anselmo Olinto, Senthil K Vasan, Sara Schramm, Xenophon Theodoridis, Moyses Szklo, Ramfis Nieto-Martínez, Viswanathan Mohan, Guillermo Frontera, Rahul Malhotra, Thomas Ferrao, Dongfeng Gu, Tomas Vega, Hynek Pikhart, Päivi Mäki, Heba Fouad, Vilnis Dzerve, Christina Howitt, Seyed Mohammad Hashemi-Shahri, Jenny M. Kindblom, Marjolijn C. E. Bragt, G. K. Mini, Qian Wang, Liufu Cui, Andrzej Galbarczyk, Sylvain Sebert, Vilmundur Gudnason, Loreto Santa Marina, Kairat Davletov, Afshin Ostovar, Niloofar Peykari, Nicholas J. Wareham, Wilma M. Hopman, Karl-Heinz Jöckel, Jussi Kauhanen, Breige A. McNulty, Alina Kerimkulova, Youcef Laid, Claes Ohlsson, Stefan Kiechl, Alicia Matijasevich, Boban Mugoša, Srinivasan Kannan, Jyrki K. Virtanen, Mohan Deepa, Mangesh S. Pednekar, Shahla AlDhukair, Cynthia M. Pérez, Vera Lanska, Tint Swe Latt, Dominique Hange, João Luiz Bastos, Eliza Markidou Ioannidou, Leticia Hernandez Cadena, Maya Tanrygulyyeva, Reza Malekzadeh, Dimitrios Poulimeneas, Pedro Ordunez, Thomas Waldhör, Ioannis Pagkalos, Carlo M. Barbagallo, Abla M. Sibai, Peter Vollenweider, Asher Fawwad, Emily Sonestedt, Elena Pahomova, Santosh K. Bhargava, Patrick Kolsteren, Aya Mostafa, Fangfang Chen, Flavio Nervi, Imre Janszky, Arvind Pandey, Renata Cifkova, Alexandre C. Pereira, Alejandro Diaz, Alireza Ansari-Moghaddam, Rachakulla Hari Kumar, Jaakko Mursu, Luis A. Moreno, Glen Gironella, Jelena Kos, Tilema Cama, Haakon E. Meyer, Jun Ma, Raphael E. Arku, Ziad Abdeen, Rusidah Selamat, Dianna J. Magliano, Jitendra Jonnagaddala, Konstantinos Gkiouras, Paul Korrovits, Paola Nardone, Paolo Vineis, Kotsedi D Monyeki, Khuong Quynh Long, Alberto Barceló, Camilla T. Damsgaard, Constance Schultsz, Frank J Rühli, Santiago F. Gomez, Tara Coppinger, Muhammad Islam, Pierre Traissac, Eleonora d'Orsi, Irfan Nuhoglu, Rui Providência, Bernard Maire, Leandra Abarca-Gómez, Sinead Brophy, Daniela Pierannunzio, Cristina Taddei, Wen-Harn Pan, Gregor Starc, Abdullah Alkandari, Saeed Dastgiri, Lien Braeckevelt, Gustavo Velasquez-Melendez, Sudhir Kowlessur, Bagher Larijani, Cynthia Robitaille, Mohamed M. Ali, Steiner Krokstad, Noor Ani Ahmad, Anar Dushpanova, Agustinus Soemantri, Susana Sans, Ionela Pascanu, Gwenaëlle Le Coroller, Inger Ariansen, Abhijit Sen, Sergej M. Ostojic, Silvana Donoso, Felix K. Assah, Juan A Rivera, Peter H. Whincup, Oana-Florentina Gheorghe-Fronea, Hanan F. Abdul Rahim, Yadlapalli S. Kusuma, Michael Knoflach, Moein Yoosefi, Cassiano Ricardo Rech, Paul Ferdinand M. Reganit, Tomi-Pekka Tuomainen, Francesco Gianfagna, Stefania Maggi, Mohammad Hossein Somi, Behrooz Hamzeh, Bethlehem D. Solomon, Herman Borghs, Zhanna Kalmatayeva, Heidi Klakk, Akram Pourshams, Naomi S. Levitt, Miquel Porta, Vesna Jureša, Alexander D. Deev, Son Thai Pham, Paula Margozzini, Silvia Bel-Serrat, Dora Romaguera, Monira Alarouj, Winsome R. Parnell, Marloes Cardol, David Faeh, Antonio Bernabe-Ortiz, Giota Touloumi, Maryam Kavousi, Sanja Musić Milanović, Jalila El Ati, Sauli Herrala, Liang Xu, Sirkka Keinänen-Kiukaanniemi, Ian Hambleton, Stefan Savin, Andre Pascal Kengne, R. Krishna Kumar, Kurt Widhalm, Marco M Ferrario, Parisa Amiri, Yi Song, Jianfeng Wu, Jeannette Klimont, Jean Ferrières, Farhad Zamani, Shina Avi, Luis Paulo Gomes Mascarenhas, Aluísio J D Barros, Reecha Sofat, Koen Van Herck, Hoang Van Minh, Enrique Gutiérrez-González, Martine Vrijheid, Susana Cararo Confortin, Antonis Zampelas, Bogdan Wojtyniak, Ausra Petrauskiene, Juha Auvinen, Maryam Sharafkhah, Emanuel Zitt, Majid Ezzati, Young-Ho Khang, Ellina Rakhimova, Magdalena Klimek, Luís Lopes, Erkin M. Mirrakhimov, Maria Lc Iurilli, Günay Can, Mark Woodward, Esther Lopez-Garcia, Mauro Virgílio Gomes de Barros, Ahmed A. Madar, Rainford J. Wilks, Shoaib Afzal, Melanie J. Cowan, Gareth Stratton, Eduardo Salazar Martinez, Sameer Narake, Norie Sawada, Li Juan Wu, Adrian Richter, Licia Iacoviello, Hanno Ulmer, Deepak Amarapurkar, Mohsen Ibrahim, Hamed Pouraram, Massimo Salvetti, Hung-Kwan So, Yonghua Hu, Lars Ängquist, Thi Tuyet-Hanh Tran, Charles Lunogelo, Sabina Zambon, Angelika Schaffrath Rosario, Lauren Lissner, Kamarul Imran Musa, Deepa Weerasekera, Bihungum Bista, Takafumi Ishida, Ekaterina Chikova-Iscener, Mirjam M. Heinen, Tazeen H. Jafar, Semánová Csilla, Raija Korpelainen, Edward W. Gregg, Laura Gutierrez, Victor M. Herrera, Aristides M. Machado-Rodrigues, Fatemeh Malekzadeh, Shouling Wu, Jennifer L. Baker, Clicerio González-Villalpando, Irene G. M. van Valkengoed, Anna Fijałkowska, Meghnath Dhimal, Murat Topbaş, George Moschonis, Robert Eggertsen, Quang Ngoc Nguyen, Janette Walton, Elnaz Faramarzi, Nasheeta Peer, Radka Taxová Braunerová, Harald Geiger, Morteza Shamshirgaran, Lela Shengelia, María Ángeles Dal Re Saavedra, Khem Bahadur Karki, Timothy J. Key, Maria G. Grammatikopoulou, Susana Vale, Bernhard O. Boehm, Songhomitra Panda-Jonas, Iveta Pudule, Elisabete Ramos, Lacramioara Aurelia Brinduse, Paul H. Lee, Terence W O'Neill, Javad Aghazadeh-Attari, Margus Punab, Bojan Jelaković, Eliza Cinteza, Ha Tp Do, and Alison J. Hayes

Subjects
education.field_of_study, business.industry, Population, Distribution (economics), medicine.disease, Obesity, Geography, medicine, Underweight, medicine.symptom, education, business, Body mass index, Demography
Published
2020

186. Cardiovascular Risk Factors in Childhood and Left Ventricular Diastolic Function in Adulthood

Author

Jorma Viikari, Päivi Tossavainen, Tomi Laitinen, Suvi P. Rovio, Katja Pahkala, Eero Jokinen, Mika Kähönen, Markus Juonala, Nina Hutri-Kähönen, Terho Lehtimäki, Jarkko S. Heiskanen, Saku Ruohonen, Ville Kytö, and Olli T. Raitakari

Subjects
Adult, Male, medicine.medical_specialty, Pediatric Obesity, Waist, Adolescent, Diastole, 03 medical and health sciences, Ventricular Dysfunction, Left, 0302 clinical medicine, 030225 pediatrics, Internal medicine, medicine, Humans, Longitudinal Studies, Risk factor, Child, Exercise, Adiposity, business.industry, Area under the curve, Middle Aged, medicine.disease, Obesity, Physical activity level, Blood pressure, Echocardiography, Heart Disease Risk Factors, Pediatrics, Perinatology and Child Health, Hypertension, Cardiology, Female, Sedentary Behavior, business, Biomarkers, Lipoprotein
Abstract

BACKGROUND AND OBJECTIVES: Cardiovascular risk factors, such as obesity, blood pressure, and physical inactivity, have been identified as modifiable determinants of left ventricular (LV) diastolic function in adulthood. However, the links between childhood cardiovascular risk factor burden and adulthood LV diastolic function are unknown. To address this lack of knowledge, we aimed to identify childhood risk factors associated with LV diastolic function in the participants of the Cardiovascular Risk in Young Finns Study. METHODS: Study participants (N = 1871; 45.9% men; aged 34–49 years) were examined repeatedly between the years 1980 and 2011. We determined the cumulative risk exposure in childhood (age 6–18 years) as the area under the curve for systolic blood pressure, adiposity (defined by using skinfold and waist circumference measurements), physical activity, serum insulin, triglycerides, total cholesterol, and high- and low-density lipoprotein cholesterols. Adulthood LV diastolic function was defined by using E/é ratio. RESULTS: Elevated systolic blood pressure and increased adiposity in childhood were associated with worse adulthood LV diastolic function, whereas higher physical activity level in childhood was associated with better adulthood LV diastolic function (P < .001 for all). The associations of childhood adiposity and physical activity with adulthood LV diastolic function remained significant (both P < .05) but were diluted when the analyses were adjusted for adulthood systolic blood pressure, adiposity, and physical activity. The association between childhood systolic blood pressure and adult LV diastolic function was diluted to nonsignificant (P = .56). CONCLUSIONS: Adiposity status and the level of physical activity in childhood are independently associated with LV diastolic function in adulthood.

Published
2020

187. Genetic studies of leptin concentrations implicate leptin in the regulation of early adiposity

Author

Daniel I. Chasman, Torben Hansen, Rebecca S. Fine, Kari E. North, Harald Grallert, Jeffrey Haesser, Jie Yao, Arund D. Pradhan, Peter Kovacs, Mariaelisa Graff, Rebecca D. Jackson, Zoltán Kutalik, James G. Wilson, Neil Robertson, Mika Kähönen, Linda S. Adair, Jennifer Kriebel, Ruth J. F. Loos, Massimo Mangino, Jayne F. Martin Carli, Yiying Zhang, M. Arfan Ikram, Paraskevi Christofidou, Linda Broer, Paul M. Ridker, Barbara McKnight, Satu Männistö, Sophia Metz, Tea Skaaby, Jette Bork-Jensen, Craig E. Pennell, Sophie Molnos, Michael A. Province, Xiuqing Guo, Laura B. L. Wittemans, Stephen J. Lye, Cornelia M. van Duijn, Samuli Ripatti, Ko Willems van Dijk, Tim Kacprowski, America A. Sandoval-Zárate, Hermina Jakupović, Tuomas O. Kilpeläinen, Michael Preuss, Jaeyoung Hong, Cristina Venturini, Ying Wu, Germán D. Carrasquilla, Ivana Prokic, Mary F. Feitosa, Melissa E. Garcia, Paul L. Auer, Leslie A. Lange, Leo-Pekka Lyytikäinen, Kristin L. Young, Tugce Karaderi, Alexander P. Reiner, Tim D. Spector, Anubha Mahajan, Claudia Schurmann, Jerome I. Rotter, Rudolph L. Leibel, Georg Homuth, Claudia A. Doege, Hakon Hakonarson, Nicholas J. Wareham, Najaf Amin, Shuai Wang, Matthias Blüher, Ayse Demirkan, Andrew P. Morris, Charles A. LeDuc, Claudia Langenberg, Hanieh Yaghootkar, Mike A. Nalls, Erik Ingelsson, Dennis O. Mook-Kanamori, Jorge R. Kizer, Carolina Medina-Gomez, Timothy M. Frayling, Colleen M. Sitlani, David A. Mackey, Bruce M. Psaty, Matthias Nauck, Struan F.A. Grant, Konstantin Strauch, Olli T. Raitakari, Alexander Teumer, Mark Walker, Jonathan P. Bradfield, Judith B. Borja, Karen L. Mohlke, Lars Lind, André G. Uitterlinden, Renée de Mutsert, Ruifang Li-Gao, Cassandra N. Spracklen, Jin Li, Anne E. Justice, Cecilia M. Lindgren, Kaiying Guo, Terho Lehtimäki, Pekka Jousilahti, Yingchang Lu, Yii-Der Ida Chen, Sara M. Willems, Tamara B. Harris, Matthew A. Allison, Carol A. Wang, Niels Grarup, Lam Opal Huang, Veikko Salomaa, Jian'an Luan, Robert A. Scott, Kent D. Taylor, James B. Meigs, Ophthalmology, Epidemiology, Internal Medicine, Clinical Genetics, Department of Organisation and Personnel Management, Health Services Management & Organisation (HSMO), Yaghootkar, Hanieh [0000-0001-9672-9477], Kilpeläinen, Tuomas O [0000-0002-8349-3028], and Apollo - University of Cambridge Repository

Subjects
0301 basic medicine, Leptin, Models, Molecular, medicine.medical_specialty, Genotype, Protein Conformation, Endocrinology, Diabetes and Metabolism, 030209 endocrinology & metabolism, Genome-wide association study, KLF14, Biology, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, Internal Medicine, medicine, Missense mutation, Humans, Allele, Exome, Adiposity, 2. Zero hunger, Racial Groups, digestive, oral, and skin physiology, Gene Expression Regulation, Developmental, Genetic Variation, Genetics/Genomes/Proteomics/Metabolomics, medicine.disease, Obesity, 030104 developmental biology, Endocrinology, hormones, hormone substitutes, and hormone antagonists
Abstract

Leptin influences food intake by informing the brain about the status of body fat stores. Rare LEP mutations associated with congenital leptin deficiency cause severe early-onset obesity that can be mitigated by administering leptin. However, the role of genetic regulation of leptin in polygenic obesity remains poorly understood. We performed an exome-based analysis in up to 57,232 individuals of diverse ancestries to identify genetic variants that influence adiposity-adjusted leptin concentrations. We identify five novel variants, including four missense variants, in LEP, ZNF800, KLHL31, and ACTL9, and one intergenic variant near KLF14. The missense variant Val94Met (rs17151919) in LEP was common in individuals of African ancestry only and its association with lower leptin concentrations was specific to this ancestry (P=2x10-16, n=3,901). Using in vitro analyses, we show that the Met94 allele decreases leptin secretion. We also show that the Met94 allele is associated with higher BMI in young African-ancestry children but not in adults, suggesting leptin regulates early adiposity.

Published
2020

188. Evolution of genetic networks for human creativity

Author

Claude Robert Cloninger, I. Tattersall, Alberto Mesa, Mirka Hintsanen, Ramiro Salas, Kevin M. Cloninger, G. F. Poblete, Javier Arnedo, Igor Zwir, Olli T. Raitakari, G. A. de Erausquin, Emma Raitoharju, Terho Lehtimäki, Liisa Keltikangas-Järvinen, Rocío Romero-Zaliz, and Coral Del-Val

Subjects
0301 basic medicine, Behavioral modernity, Pan troglodytes, media_common.quotation_subject, Biology, Genome, Creativity, Evolution, Molecular, 03 medical and health sciences, Cellular and Molecular Neuroscience, 0302 clinical medicine, Genetics, Personality, Animals, Humans, Gene Regulatory Networks, Association (psychology), Molecular Biology, Gene, media_common, Human evolution, Neanderthals, Autobiographical memory, Brain, Psychiatry and Mental health, 030104 developmental biology, Prosocial behavior, Evolutionary biology, RNA, Long Noncoding, 030217 neurology & neurosurgery
Abstract

The genetic basis for the emergence of creativity in modern humans remains a mystery despite sequencing the genomes of chimpanzees and Neanderthals, our closest hominid relatives. Data-driven methods allowed us to uncover networks of genes distinguishing the three major systems of modern human personality and adaptability: emotional reactivity, self-control, and self-awareness. Now we have identified which of these genes are present in chimpanzees and Neanderthals. We replicated our findings in separate analyses of three high-coverage genomes of Neanderthals. We found that Neanderthals had nearly the same genes for emotional reactivity as chimpanzees, and they were intermediate between modern humans and chimpanzees in their numbers of genes for both self-control and self-awareness. 95% of the 267 genes we found only in modern humans were not protein-coding, including many long-non-coding RNAs in the self-awareness network. These genes may have arisen by positive selection for the characteristics of human well-being and behavioral modernity, including creativity, prosocial behavior, and healthy longevity. The genes that cluster in association with those found only in modern humans are over-expressed in brain regions involved in human self-awareness and creativity, including late-myelinating and phylogenetically recent regions of neocortex for autobiographical memory in frontal, parietal, and temporal regions, as well as related components of cortico-thalamo-ponto-cerebellar-cortical and cortico-striato-cortical loops. We conclude that modern humans have more than 200 unique non-protein-coding genes regulating co-expression of many more proteincoding genes in coordinated networks that underlie their capacities for self-awareness, creativity, prosocial behavior, and healthy longevity, which are not found in chimpanzees or Neanderthals.

Published
2020

189. Novel loci for childhood body mass index and shared heritability with adult cardiometabolic traits

Author

Inês Barroso, Peter D. Sly, Jose Ramon Bilbao, Nicholas J. Timpson, Johan G. Eriksson, Maria M. Groen-Blokhuis, Sijmen A. Reijneveld, Dariusz Gruszfeld, George Davey Smith, Christine Power, Eva Reischl, Mandy Vogel, Andrew T. Hattersley, Øyvind Helgeland, Niina Pitkänen, Akram Alyass, Jean-Paul Langhendries, Elina Hyppönen, Kathrin Landgraf, Loreto Santa-Marina, Frank Geller, Christopher D. Brown, Elvira Verduci, Katja Pahkala, Olli T. Raitakari, Joaquin Escribano, Torben Hansen, Hakon Hakonarson, Barbara Heude, Bridget A. Knight, Maties Torrent, Robin N Beaumont, Judith M. Vonk, Estelle Lowry, Patrick G. Holt, Harold Snieder, Carol A. Wang, Mark I. McCarthy, Christine Frithioff-Bøjsøe, Tanja G. M. Vrijkotte, Natalia Vilor-Tejedor, Lisbeth Carstensen, Catharina E. M. van Beijsterveldt, Ville Karhunen, Virpi Lindi, Marjo-Riitta Järvelin, Tarunveer S. Ahluwalia, Jordi Sunyer, Jaakko T. Leinonen, Clare S. Murray, Klaus Bønnelykke, Thorkild I. A. Sørensen, André G. Uitterlinden, Janine F. Felix, John A. Curtin, Mika Kähönen, Jorma Viikari, Leo-Pekka Lyytikäinen, Oluf Pedersen, Carmen Iñiguez, Harri Niinikoski, Wieland Kiess, Kim F. Michaelsen, Evie Stergiakouli, Anni Heiskala, Alessandra Chesi, Craig E. Pennell, Mohammed H Zafarmand, Peter Rzehak, Kook K Teo, Aihuali Li, Marie Standl, Veit Grote, Momoko Horikoshi, Ellen A. Nohr, Eleanor Wheeler, Rachel M. Freathy, Iryna O. Fedko, Gerard H. Koppelman, Elisabeth Widen, Jens-Christian Holm, Raimo Joro, David Meyre, Mustafa Atalay, Theresia M. Schnurr, Camilla Schmidt Morgen, Adnan Custovic, Niels Grarup, Trevor A. Mori, Terho Lehtimäki, Christian Theil Have, Angela Simpson, Mads Melbye, Bjarke Feenstra, Lawrence J. Beilin, Stefan Johansson, Ioanna Ntalla, Martine Vrijheid, Mariona Bustamante, George Dedoussis, Sylvain Sebert, Jonas Bacelis, Carolina Medina-Gomez, Elisabeth Thiering, Ken K. Ong, Eleftheria Zeggini, Berthold Koletzko, Karine Clément, Bo L. Chawes, Mette Hollensted, Babette S. Zemel, Markus Scholz, Holger Kirsten, Antje Körner, Albertine J. Oldehinkel, Barbera D. C. van Schaik, Philippe Froguel, Vincent W. V. Jaddoe, Dorret I. Boomsma, Struan F.A. Grant, Loic Yengo, Jonathan P. Bradfield, Tenna Ruest Haarmark Nielsen, Suzanne Vogelezang, Jakob Stokholm, Pål R. Njølstad, Bo Jacobsson, Marc Vaudel, Peter J. van der Most, Andreas Kühnapfel, Mads Vendelbo Lind, Timo A. Lakka, Saskia Selzam, Robert Plomin, Marie-Aline Charles, Jouke-Jan Hottenga, Kalliope Panoutsopoulou, Fernando Rivadeneira, Rebecca K. Vinding, Hans Bisgaard, I. S. Farooqi, Joachim Heinrich, Diana L. Cousminer, Ricardo Closa-Monasterolo, Claire Monnereau, European Commission, Epidemiology, Erasmus MC other, Pediatrics, Internal Medicine, Epidemiology and Data Science, ACS - Atherosclerosis & ischemic syndromes, APH - Aging & Later Life, APH - Global Health, APH - Health Behaviors & Chronic Diseases, APH - Personalized Medicine, ARD - Amsterdam Reproduction and Development, APH - Methodology, AGEM - Amsterdam Gastroenterology Endocrinology Metabolism, ACS - Amsterdam Cardiovascular Sciences, Public and occupational health, Erasmus University Medical Center [Rotterdam] (Erasmus MC), Children’s Hospital of Philadelphia (CHOP ), Herlev and Gentofte Hospital, Manchester Academic Health Science Centre (MAHSC), University of Manchester [Manchester], University of Kuopio, University of Copenhagen = Københavns Universitet (KU), Universität Leipzig [Leipzig], University Medical Center Groningen [Groningen] (UMCG), University of Bristol [Bristol], Université d'Oulu, The Wellcome Trust Centre for Human Genetics [Oxford], University of Oxford [Oxford], Vrije Universiteit Brussel (VUB), CIBER de Epidemiología y Salud Pública (CIBERESP), Helmholtz-Zentrum München (HZM), University of Newcastle [Australia] (UoN), Turku University Hospital (TYKS), Statens Serum Institut [Copenhagen], Sahlgrenska Academy at University of Gothenburg [Göteborg], Metabolic functional (epi)genomics and molecular mechanisms involved in type 2 diabetes and related diseases - UMR 8199 - UMR 1283 (GI3M), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre National de la Recherche Scientifique (CNRS)-Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP), Queen Mary University of London (QMUL), Norwegian Institute of Public Health [Oslo] (NIPH), King‘s College London, University of Groningen [Groningen], University of Amsterdam [Amsterdam] (UvA), Centre de Recherche Épidémiologie et Statistique Sorbonne Paris Cité (CRESS (U1153 / UMR_A_1125 / UMR_S_1153)), Conservatoire National des Arts et Métiers [CNAM] (CNAM)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), University of Cambridge [UK] (CAM), McMaster University [Hamilton, Ontario], University of Exeter, Ludwig-Maximilians-Universität München (LMU), University of the Basque Country [Bizkaia] (UPV/EHU), The Wellcome Trust Sanger Institute [Cambridge], The University of Western Australia (UWA), Nutrition et obésités: approches systémiques (nutriomics) (UMR-S 1269 INSERM - Sorbonne Université), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Universitat Rovira i Virgili, Imperial College London, University of Helsinki, Vrije Universiteit Amsterdam [Amsterdam] (VU), University College of London [London] (UCL), University of Bergen (UiB), University of Tampere [Finland], University of Oulu, Copenhagen University Hospital, University of Turku, University of Queensland [Brisbane], Haukeland University Hospital, Università degli Studi di Milano-Bicocca [Milano] (UNIMIB), National Institute for Health Research Biomedical Research Centre at Great Ormond Street Hospital for Children NHS Foundation Trust University College London Wellcome 090532106130098381203141212259WT206194United States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Institute of Diabetes & Digestive & Kidney Diseases (NIDDK)U01DK105535National Institute for Health Research (NIHR)NF-SI-0617-10090Netherlands Organization for Health Research and DevelopmentTOP 40-00812-9811010American Diabetes Association1-17-PDF-077Daniel B. Burke Chair for Diabetes Research United States Department of Health & Human ServicesNational Institutes of Health (NIH) - USAR01 HD058886Agencia de Gestio D'Ajuts Universitaris de Recerca Agaur (AGAUR)2017 FI_B 00636Generalitat de Catalunya -Fons Social Europeu European Research Council Advanced Grant META-GROWTH (ERC-2012-AdG) 322605Oak Foundation Fellowship Wellcome TrustEuropean CommissionWT104150098497/Z/12/ZRoyal Society of LondonEuropean CommissionWT104150Wellcome Trust098395/Z/12/ZNatural Resources CanadaCanadian Forest ServiceCanada Research Chairs Finnish Cultural Foundation KNAW Academy Professor Award PAH/6635TARGET Danish Diabetes Academy Copenhagen Graduate School of Health and Medical Sciences Netherlands Organization for Health Research and Development (VIDI) 016.136.361European Research Council (ERC)European Commission648916European Research Council (ERC)European Commission UK Research & Innovation (UKRI)Medical Research Council UK (MRC)European CommissionMRC_MC_UU_12012/5MC_UU_00011/1National Institute for Health Research (NIHR) Botnar Foundation Bernard Wolfe Health Neuroscience Endowment European Community's Seventh Framework Programme (FP7/2007-2013) project Beta-JUDO 279153University of Bristol UK Research & Innovation (UKRI)Medical Research Council UK (MRC)MC_UU_00011/1MC_UU_00011/3French National Agency of Research, F-CRIN/FORCE, Clinicum, Johan Eriksson / Principal Investigator, Department of General Practice and Primary Health Care, Helsinki University Hospital Area, Genomics of Sex Differences, Institute for Molecular Medicine Finland, Centre of Excellence in Complex Disease Genetics, Elisabeth Ingrid Maria Widen / Principal Investigator, Genomic Discoveries and Clinical Translation, University of Copenhagen = Københavns Universitet (UCPH), Universität Leipzig, University of Oxford, Helmholtz Zentrum München = German Research Center for Environmental Health, University of Newcastle [Callaghan, Australia] (UoN), Metabolic functional (epi)genomics and molecular mechanisms involved in type 2 diabetes and related diseases - UMR 8199 - UMR 1283 (EGENODIA (GI3M)), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre National de la Recherche Scientifique (CNRS), Conservatoire National des Arts et Métiers [CNAM] (CNAM), HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), University of the Basque Country/Euskal Herriko Unibertsitatea (UPV/EHU), Nutrition et obésités: approches systémiques (UMR-S 1269) (Nutriomics), Helsingin yliopisto = Helsingfors universitet = University of Helsinki, Università degli Studi di Milano-Bicocca = University of Milano-Bicocca (UNIMIB), Felix, Janine F [0000-0002-9801-5774], Apollo - University of Cambridge Repository, Biological Psychology, APH - Mental Health, Felix, Janine F. [0000-0002-9801-5774], Tampere University, Tampere University Hospital Catchment Area, Department of Clinical Physiology and Nuclear Medicine, Clinical Medicine, Department of Clinical Chemistry, Groningen Research Institute for Asthma and COPD (GRIAC), Public Health Research (PHR), Life Course Epidemiology (LCE), Vogelezang, Suzanne, Bradfield, Jonathan P, Ahluwalia, Tarunveer S, Curtin, John A, Hyppönen, Elina, Felix, JF, and Early Growth Genetics Consortium

Subjects
Male, Genetic-variation, Nedd4 Ubiquitin Protein Ligases, Pooled Analysis, Blood Pressure, 0302 clinical medicine, Human genetics, Mendelian Randomization, Young adult, Child, health care economics and organizations, Body mass index, Adiposity, Genetics & Heredity, 0303 health sciences, Statistics, 1184 Genetics, developmental biology, physiology, Genomics, adulto, 3. Good health, Cardiovascular Diseases, Child, Preschool, Physical Sciences, Menarche, genetic-variation, presión sanguínea, Monosaccharide Transport Proteins, Genetic loci, education, enfermedades cardiovasculares, Prostate-specific Antigen, Genetic correlation, 03 medical and health sciences, SDG 3 - Good Health and Well-being, Diabetes Mellitus, Genetics, Humans, prostate-specific antigen, Statistical Methods, Molecular Biology, Ecology, Evolution, Behavior and Systematics, childhood, 0604 Genetics, [SDV.GEN]Life Sciences [q-bio]/Genetics, Science & Technology, Early Growth Genetics Consortium, Biology and Life Sciences, Computational Biology, nutritional and metabolic diseases, Single nucleotide polymorphisms, Mendelian Randomization Analysis, Biological Tissue, Diabetes Mellitus, Type 2, estudio de asociación genómica completa, genetic factors, mendelian randomization, análisis de la aleatorización mendeliana, proteínas de transporte de monosacáridos, 030217 neurology & neurosurgery, Mathematics, Demography, Developmental Biology, Cardiovascular Risk, Cancer Research, obesity, Physiology, humanos, adolescente, Overweight, QH426-470, Genome-wide association studies, Waist–hip ratio, Mathematical and Statistical Techniques, Medicine and Health Sciences, body mass index (BMI), Genetics of disease, Genetics (clinical), 2. Zero hunger, adiposity, Metaanalysis, Physiological Parameters, Connective Tissue, Female, medicine.symptom, Anatomy, pooled analysis, Life Sciences & Biomedicine, Research Article, Adult, cardiovascular risk, Adolescent, Birth weight, menarquia, Adipose tissue, Biology, 3121 Internal medicine, Research and Analysis Methods, medicine, overweight, Genetic Predisposition to Disease, Obesity, 030304 developmental biology, Waist-Hip Ratio, índice de masa corporal, Body Weight, Cardiometabolic Risk Factors, predisposición genética a la enfermedad, Heritability, Genome Analysis, young-adults, Genome-wide Association, índice cintura-cadera, Young-adults, genome-wide association, Genome-Wide Association Study
Abstract

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, CP received funding from the National Institute for Health Research Biomedical Research Centre at Great Ormond Street Hospital for Children NHS Foundation Trust and University College London. MMcC is a Wellcome Senior Investigator and an NIHR Senior Investigator. MMcC received funding from Wellcome (090532, 106130, 098381, 203141, 212259), NIDDK (U01DK105535), and NIHR (NF-SI-0617-10090). TGMV was supported by ZonMW (TOP 40-00812-9811010). DLC was supported by the American Diabetes Association Grant 1-17-PDF-077. SFAG is supported by the Daniel B. Burke Chair for Diabetes Research and NIH Grant R01 HD058886. NVT is funded by a pre-doctoral grant from the Agencia de Gestio d'Ajuts Universitaris i de Recerca (2017 FI_B 00636), Generalitat de Catalunya -Fons Social Europeu. BK received personal funding from the European Research Council Advanced Grant META-GROWTH (ERC-2012-AdG -no. 322605). BF was supported by an Oak Foundation Fellowship. RMF and RNB are supported by Sir Henry Dale Fellowship (Wellcome Trust and Royal Society grant: WT104150). ATH is supported by a Wellcome Trust Senior Investigator award (grant number 098395/Z/12/Z). DM is supported by a Canada Research Chair. DLC was supported by the American Diabetes Association Grant 1-17-PDF077. JTL was supported by the Finnish Cultural Foundation. DIB received a KNAW Academy Professor Award (PAH/6635). MH received PhD scholarship funding from TARGET (http://target.ku.dk), The Danish Diabetes Academy (http://danishdiabetesacademy.dk) and the Copenhagen Graduate School of Health and Medical Sciences. VWVJ received funding from the Netherlands Organization for Health Research and Development (VIDI 016.136.361) and the European Research Council (ERC-2014-CoG-648916). ISF was supported by the European Research Council, Wellcome Trust (098497/Z/12/Z), Medical Research Council (MRC_MC_UU_12012/5), the NIHR Cambridge Biomedical Research Centre, the Botnar Foundation, the Bernard Wolfe Health Neuroscience Endowment and the European Community's Seventh Framework Programme (FP7/2007-2013) project Beta-JUDO n degrees 279153. IB acknowledges funding from Wellcome (WT206194). ES works in a unit that receives funding from the University of Bristol and the UK Medical Research Council (MC_UU_00011/1, MC_UU_00011/3). GDS works in the Medical Research Council Integrative Epidemiology Unit at the University of Bristol, which is supported by the Medical Research Council (MC_UU_00011/1). KC received funds from the French National Agency of Research, F-CRIN/FORCE. All funding for the studies that provided the underlying data for this manuscript can be found in S1 Text. The funders had no role in study design, data collection and analysis, data interpretation, decision to publish, or preparation of the manuscript.

Published
2020

190. Examining the effect of mitochondrial DNA variants on blood pressure in two Finnish cohorts

Author

Pekka Ellonen, Jukka T. Salonen, Mika Kähönen, Maija Lepistö, Ilkka Seppälä, Nina Hutri-Kähönen, Pashupati P. Mishra, Leo-Pekka Lyytikäinen, Emma Raitoharju, Olli T. Raitakari, Nina Mononen, Terho Lehtimäki, Jaakko Laaksonen, Markus Juonala, Henrikki Almusa, Tampere University, Clinical Medicine, Department of Clinical Chemistry, Department of Paediatrics, Department of Clinical Physiology and Nuclear Medicine, Institute for Molecular Medicine Finland, University of Helsinki, and Department of Public Health

Subjects
0301 basic medicine, Adult, Male, Mitochondrial DNA, Genotype, Science, Single-nucleotide polymorphism, Blood Pressure, 030204 cardiovascular system & hematology, Biology, 3121 Internal medicine, DNA, Mitochondrial, Polymorphism, Single Nucleotide, Genome-wide association studies, Article, Cohort Studies, 03 medical and health sciences, 0302 clinical medicine, Mitochondrial genome, Risk Factors, SNP, Humans, Risk factor, Finland, Genetics, Multidisciplinary, Middle Aged, Pathogenicity, Peripheral blood, 3142 Public health care science, environmental and occupational health, 3. Good health, Mitochondria, 030104 developmental biology, Blood pressure, Phenotype, 3121 General medicine, internal medicine and other clinical medicine, Transfer RNA, Genome, Mitochondrial, Hypertension, Medicine, Female, 3111 Biomedicine, Genome-Wide Association Study
Abstract

High blood pressure (BP) is a major risk factor for many noncommunicable diseases. The effect of mitochondrial DNA single-nucleotide polymorphisms (mtSNPs) on BP is less known than that of nuclear SNPs. We investigated the mitochondrial genetic determinants of systolic, diastolic, and mean arterial BP. MtSNPs were determined from peripheral blood by sequencing or with genome-wide association study SNP arrays in two independent Finnish cohorts, the Young Finns Study and the Finnish Cardiovascular Study, respectively. In total, over 4200 individuals were included. The effects of individual common mtSNPs, with an additional focus on sex-specificity, and aggregates of rare mtSNPs grouped by mitochondrial genes were evaluated by meta-analysis of linear regression and a sequence kernel association test, respectively. We accounted for the predicted pathogenicity of the rare variants within protein-encoding and the tRNA regions. In the meta-analysis of 87 common mtSNPs, we did not observe significant associations with any of the BP traits. Sex-specific and rare-variant analyses did not pinpoint any significant associations either. Our results are in agreement with several previous studies suggesting that mtDNA variation does not have a significant role in the regulation of BP. Future studies might need to reconsider the mechanisms thought to link mtDNA with hypertension.

Published
2020

191. Estimated PCDD/F TEQ and total TEQ concentrations in the serum of 7-10 year old Finnish children

Author

Hannu Kiviranta, Jouni T. Tuomisto, Panu Rantakokko, Jouko Tuomisto, Anne M. Karvonen, Matti Viluksela, Olli T. Raitakari, Riikka Airaksinen, Juha Pekkanen, Department of Public Health, and University of Helsinki

Subjects
Polychlorinated Dibenzodioxins, Health, Toxicology and Mutagenesis, 0208 environmental biotechnology, 02 engineering and technology, 010501 environmental sciences, 01 natural sciences, POLYCHLORINATED-BIPHENYLS, Medicine, European food safety authority (EFSA), Child, Finland, General Medicine, Polychlorinated Biphenyls, Pollution, 3142 Public health care science, environmental and occupational health, 3. Good health, 1181 Ecology, evolutionary biology, Environmental Pollutants, Dibenzofurans, Risk assessment, Adult, Environmental Engineering, No-observed-adverse-effect level, Adolescent, Food Contamination, Dioxins, Risk Assessment, Young Adult, Animal science, PCDD/Fs, Humans, Environmental Chemistry, ELIMINATION HALF-LIVES, EXPOSURE, Impaired semen quality, Benzofurans, 0105 earth and related environmental sciences, Tolerable weekly intake, Milk, Human, business.industry, Small volume, DIBENZO-P-DIOXINS, Public Health, Environmental and Occupational Health, Bayes Theorem, Environmental Exposure, General Chemistry, Dibenzofurans, Polychlorinated, Diet, 020801 environmental engineering, 13. Climate action, PCBS, business
Abstract

Polychlorinated dibenzo-p-dioxins and furans (PCDD/Fs) and polychlorinated biphenyls (PCBs) are persistent organic pollutants that have detrimental health effects. As people are exposed to them mainly through the diet, EU has set maximum food dioxin and PCBs levels. EFSA CONTAM Panel made new risk assessment in 2018 that lowered the tolerable weekly intake (TWI) from 14 pg-TEQ/kg bw/week to 2 pgTEQ/kg bw/week. Critical effect was decreased semen count at the age of 18-19 years if serum total TEQ at the age of 9 years exceeded the No Observed Adverse Effect Level (NOAEL) of 7 pg/g lipid. However, it is largely unknown to what extent NOAEL is exceed in European boys currently. We thus measured PCBs from small volume of serum in 184 Finnish children 7-10 years of age. To estimate the TEQ levels of children from measured PCB levels, we used our existing human milk PCDD/F and PCB concentrations to create a hierarchical Bayesian regression model that was used to estimate TEQs from measured PCBs. For quality control (QC), three pooled blood samples from 18 to 20 year old males were measured for PCDD/Fs and PCBs, and estimated for TEQs. In QC samples measured and estimated TEQs agreed within 84% -106%. In our estimate for 7-10 year old children, PCDD/F TEQ exceeded NOAEL only in 0.5% and total TEQ in 2.7% of subjects. Risk management following the decreased TWI proposed by the CONTAM Panel should be carefully considered if total TEQ in children is already largely below the NOAEL. (C) 2020 Elsevier Ltd. All rights reserved.

Published
2020

192. Elevated glycoprotein acetyl levels in adolescence and early adulthood predict adverse cardiometabolic profiles and risk of metabolic syndrome in up to 10 year follow-up

Author

Olli T. Raitakari, Nicholas J. Timpson, Simon J. Stafford, Mika Kähönen, Georgios Georgiopoulos, Mika Ala-Korpela, Chloe Park, Justin D. Roberts, Terho Lehtimäki, Marietta Charakida, Scott T Chiesa, Alun D. Hughes, Naveed Sattar, John E. Deanfield, and Juha Mykkänen

Subjects
Longitudinal study, medicine.medical_specialty, Waist, business.industry, medicine.disease, Blood pressure, Insulin resistance, Internal medicine, Cohort, medicine, Biomarker (medicine), Metabolic syndrome, Young adult, business
Abstract

ObjectiveLow-grade inflammation in the young may contribute to the early development of adverse cardiometabolic risk profiles. We assessed whether measures of glycoprotein acetylation (GlycA) were better able to detect the development of these changes compared to the more commonly used biomarker high-sensitivity C-reactive protein (CRP), and investigated whether these relationships differed in an adolescent compared to young adult cohort.Research Design and MethodsA total of 3306 adolescents (Avon Longitudinal Study of Parents and Children - ALSPAC; mean age 15.4±0.3; n=1750) and young adults (Cardiovascular Risk in Young Finns Study - YFS; mean age 32.1±5.0; n=1556) were included. Inflammatory biomarkers (GlycA/CRP), body composition (BMI / waist circumference) and cardiometabolic risk factors (blood pressure, triglycerides, HDL-c, glucose, insulin, and homeostasis model of insulin resistance [HOMA_IR]), were measured at baseline and again in 9-10 year follow-up. Metabolic Syndrome (MetS) was defined using adolescent-specific National Cholesterol Education Programme (NCEP) guidelines in ALSPAC and standard NCEP guidelines in YFS.ResultsGlycA levels showed greater within-subject correlation over the 9-10 year duration of follow-up in both cohorts when compared to CRP, particularly in the younger adolescent group. In adjusted models, only GlycA was found to increase in line with cardiometabolic risk factor burden at baseline, and to predict adverse changes in several cardiometabolic risk factors in follow-up. In both cohorts, GlycA predicted future risk of MetS (OR [95%CI] for Q4 vs. Q1 = 1.95 [1.08,3.53] and 2.74 [1.30,5.73] for ALSPAC and YFS, respectively), whereas CRP showed a neutral or even negative relationship in fully-adjusted models (OR [95%CI] = 0.50 [0.29,0.86] and 0.93 [0.53,1.64]).ConclusionsChronic inflammation is associated with adverse cardiometabolic risk profiles from as early as adolescence and predicts risk of future cardiometabolic risk and MetS in up to 10 year follow-up. GlycA may be a more sensitive inflammatory biomarker to CRP for detecting early cardiometabolic and cardiovascular risk in the young.

Published
2020

193. Refining Attention-Deficit/Hyperactivity Disorder and Autism Spectrum Disorder Genetic Loci by Integrating Summary Data From Genome-wide Association, Gene Expression, and DNA Methylation Studies

Author

Anke R. Hammerschlag, Enda M. Byrne, Meike Bartels, Naomi R. Wray, Christel M. Middeldorp, Mawussé Agbessi, Habibul Ahsan, Isabel Alves, Anand Andiappan, Wibowo Arindrarto, Philip Awadalla, Alexis Battle, Frank Beutner, Marc Jan Bonder, Dorret I. Boomsma, Mark Christiansen, Annique Claringbould, Patrick Deelen, Tõnu Esko, Marie-Julie Favé, Lude Franke, Timothy Frayling, Sina A. Gharib, Gregory Gibson, Bastiaan T. Heijmans, Gibran Hemani, Rick Jansen, Mika Kähönen, Anette Kalnapenkis, Silva Kasela, Johannes Kettunen, Yungil Kim, Holger Kirsten, Peter Kovacs, Knut Krohn, Jaanika Kronberg-Guzman, Viktorija Kukushkina, Zoltan Kutalik, Bernett Lee, Terho Lehtimäki, Markus Loeffler, Urko M. Marigorta, Hailang Mei, Lili Milani, Grant W. Montgomery, Martina Müller-Nurasyid, Matthias Nauck, Michel Nivard, Brenda Penninx, Markus Perola, Natalia Pervjakova, Brandon L. Pierce, Joseph Powell, Holger Prokisch, Bruce M. Psaty, Olli T. Raitakari, Samuli Ripatti, Olaf Rotzschke, Sina Rüeger, Ashis Saha, Markus Scholz, Katharina Schramm, Ilkka Seppälä, Eline P. Slagboom, Coen D.A. Stehouwer, Michael Stumvoll, Patrick Sullivan, Peter A.C. ‘t Hoen, Alexander Teumer, Joachim Thiery, Lin Tong, Anke Tönjes, Jenny van Dongen, Maarten van Iterson, Joyce van Meurs, Jan H. Veldink, Joost Verlouw, Peter M. Visscher, Uwe Völker, Urmo Võsa, Harm-Jan Westra, Cisca Wijmenga, Hanieh Yaghootkar, Jian Yang, Biao Zeng, Futao Zhang, Aaron Isaacs, René Pool, Jouke J. Hottenga, Marleen MJ. van Greevenbroek, Carla J.H. van der Kallen, Casper G. Schalkwijk, Sasha Zhernakova, Ettje F. Tigchelaar, P. Eline Slagboom, Marian Beekman, Joris Deelen, Diana van Heemst, Leonard H. van den Berg, Cornelia M. van Duijn, Bert A. Hofman, André G. Uitterlinden, P. Mila Jhamai, Michael Verbiest, H.Eka D. Suchiman, Marijn Verkerk, Ruud van der Breggen, Jeroen van Rooij, Nico Lakenberg, Michiel van Galen, Jan Bot, Daria V. Zhernakova, Peter van ‘t Hof, Irene Nooren, Matthijs Moed, Martijn Vermaat, René Luijk, Freerk van Dijk, Szymon M. Kielbasa, Morris A. Swertz, Erik. W. van Zwet, Peter-Bram ‘t Hoen, MUMC+: Centrum voor Chronische Zieken (3), MUMC+: MA Med Staf Artsass Interne Geneeskunde (9), RS: Carim - V01 Vascular complications of diabetes and metabolic syndrome, MUMC+: HVC Pieken Maastricht Studie (9), Interne Geneeskunde, MUMC+: MA Interne Geneeskunde (3), Urology, Medical Informatics, Department of Marketing Management, Epidemiology, Internal Medicine, Dermatology, Ophthalmology, Psychiatry, Amsterdam Neuroscience - Complex Trait Genetics, APH - Mental Health, VU University medical center, Clinical chemistry, Human genetics, APH - Digital Health, APH - Methodology, Biological Psychology, APH - Personalized Medicine, and APH - Health Behaviors & Chronic Diseases

Subjects
0301 basic medicine, Candidate gene, mQTL, Autism Spectrum Disorder, Gene Expression, Genome-wide association study, Biology, Quantitative trait locus, VARIANTS, eQTL, 03 medical and health sciences, 0302 clinical medicine, Mendelian randomization, mental disorders, Humans, GWAS, BRAIN, Biological Psychiatry, Genetic association, Genetics, Regulation of gene expression, Pleiotropy, HERITABILITY, dNaM, DNA Methylation, SMR, Fetal brain, PREVALENCE, 030104 developmental biology, Attention Deficit Disorder with Hyperactivity, DNA methylation, 17Q21.31, Psychiatric disorders, 030217 neurology & neurosurgery, Genome-Wide Association Study
Abstract

BACKGROUND: Recent genome-wide association studies (GWASs) identified the first genetic loci associated with attention-deficit/hyperactivity disorder (ADHD) and autism spectrum disorder (ASD). The next step is to use these results to increase our understanding of the biological mechanisms involved. Most of the identified variants likely influence gene regulation. The aim of the current study is to shed light on the mechanisms underlying the genetic signals and prioritize genes by integrating GWAS results with gene expression and DNA methylation (DNAm) levels.METHODS: We applied summary-data-based Mendelian randomization to integrate ADHD and ASD GWAS data with fetal brain expression and methylation quantitative trait loci, given the early onset of these disorders. We also analyzed expression and methylation quantitative trait loci datasets of adult brain and blood, as these provide increased statistical power. We subsequently used summary-data-based Mendelian randomization to investigate if the same variant influences both DNAm and gene expression levels.RESULTS: We identified multiple gene expression and DNAm levels in fetal brain at chromosomes 1 and 17 that were associated with ADHD and ASD, respectively, through pleiotropy at shared genetic variants. The analyses in brain and blood showed additional associated gene expression and DNAm levels at the same and additional loci, likely because of increased statistical power. Several of the associated genes have not been identified in ADHD and ASD GWASs before.CONCLUSIONS: Our findings identified the genetic variants associated with ADHD and ASD that likely act through gene regulation. This facilitates prioritization of candidate genes for functional follow-up studies.

Published
2020

194. Attainment of Targets of the 20-Year Infancy-Onset Dietary Intervention and Blood Pressure Across Childhood and Young Adulthood: The Special Turku Coronary Risk Factor Intervention Project (STRIP)

Author

Matthew A. Sabin, Costan G. Magnussen, David Burgner, Jorma Viikari, Eero Jokinen, Harri Niinikoski, Katja Pahkala, Joel Nuotio, Olli T. Raitakari, Tomi T. Laitinen, Hanna Lagström, Tapani Rönnemaa, Markus Juonala, Olli Simell, Antti Jula, and Suvi P. Rovio

Subjects
Male, medicine.medical_specialty, Pediatrics, DASH diet, Adolescent, Blood Pressure, 030204 cardiovascular system & hematology, Body Mass Index, 03 medical and health sciences, Young Adult, 0302 clinical medicine, Risk Factors, Intervention (counseling), Epidemiology, Internal Medicine, medicine, Humans, 030212 general & internal medicine, Prospective Studies, Young adult, Child, 2. Zero hunger, business.industry, Infant, Middle age, Blood pressure, Intima-media thickness, Heart Disease Risk Factors, Coronary risk, Child, Preschool, Female, Diet, Healthy, business
Abstract

We examined whether success in achieving the key targets of an infancy-onset 20-year dietary intervention was associated with blood pressure (BP) from infancy to young adulthood. In the prospective randomized STRIP (Special Turku Coronary Risk Factor Intervention Project; n=877 children), dietary counseling was provided biannually based on the Nordic Nutrition Recommendations primarily to improve the quality of dietary fat in children’s diets and secondarily to promote intake of vegetables, fruits, and whole grains. Dietary data and BP were accrued annually from the age of 13 months to 20 years. The dietary targets for fat quality were defined as the ratio of saturated fatty acids to monounsaturated and polyunsaturated fatty acids P =0.03) and diastolic BP (mean [SE] diastolic BP, 60.4 [0.2], 60.5 [0.2], 59.9 [0.2], and 59.9 [0.3] mm Hg; P =0.02). When the lowest age-specific quintile of dietary cholesterol was added as an additional target, the association with systolic BP remained significant ( P =0.047), but the association with diastolic BP attenuated ( P =0.13). Achieving the key targets of an infancy-onset 20-year dietary intervention, reflecting dietary guidelines, was favorably albeit modestly associated with systolic and diastolic BP from infancy to young adulthood. Registration— URL: https://www.clinicaltrials.gov ; Unique identifier: NCT00223600.

Published
2020

195. Childhood Body Mass Index and Fasting Glucose and Insulin Predict Adult Type-2 Diabetes: The International Childhood Cardiovascular Cohort (i3C) Consortium

Author

Julia Steinberger, Jessica G. Woo, Alison Venn, Elaine M. Urbina, Olli T. Raitakari, Ronald J. Prineas, Kari A. Murdy, Markus Juonala, Nina Hutri-Kähönen, Terry Dwyer, Stephen R. Daniels, Trudy L. Burns, Lydia A. Bazzano, Alan R. Sinaiko, David R. Jacobs Jr., and Tian Hu

Subjects
nutritional and metabolic diseases
Abstract

Objective: To examine childhood body mass index (BMI), fasting glucose and insulin in relation to incident adult type-2 diabetes mellitus (T2DM). Research Design and Methods: We used data from The International Childhood Cardiovascular Cohort Consortium. Data included childhood measurements (age 3-19) obtained during the 1970s-90s, a health questionnaire including self-report of adult T2DM (occurrence age, medication use) obtained at mean age 40 years, and a medical diagnosis registry (Finland). Results: The sample included 6,738 participants. Of these, 436 (6.5%) reported onset of T2DM between ages 20-59 (mean 40.8) years, and 86% of them reported use of a confirmed anti-diabetic medication. BMI and glucose (age- and sex-standardized) were associated with incident T2DM after adjustment for cohort, country, sex, race, age and calendar year of measurement. Increasing levels of childhood BMI and glucose were related to incrementally increased risk of T2DM beginning at age 30, beginning at cut points below the 95th percentile for BMI and below 100 mg/dL for glucose. Insulin was positively associated with adult T2DM after adjustment for BMI and glucose and added to T2DM discrimination. Conclusions: Childhood BMI and glucose are predictors of adult T2DM at levels previously considered to be within the normal range. These easy to apply measurements are appealing from a clinical perspective. Fasting insulin has the potential to be an additional predictor.

Published
2020

196. Metabolic profiles of socio-economic position: a multi-cohort analysis

Author

Yoav Ben-Shlomo, Usha Menon, Reecha Sofat, Alice R Carter, Alun D. Hughes, Aroon D. Hingorani, Therese Tillin, Chung-Ho E Lau, Mika Kähönen, Olli T. Raitakari, Julie Taylor, Juan P Casas, Jorgen Engmann, Jorma Viikari, Stephanie Smith, Tina Shah, Terho Lehtimäki, Marjo-Riitta Järvelin, Oliver Robinson, Mika Ala-Korpela, Nishi Chaturvedi, Laura D Howe, Ville Karhunen, Paolo Vineis, Rui Providência, Mika Kivimäki, Andy Ryan, Andrew Wong, Diana Kuh, Medical Research Council (MRC), UNIVERSITY OF OULU, Tampere University, Department of Clinical Physiology and Nuclear Medicine, Clinical Medicine, and Department of Clinical Chemistry

Subjects
Epidemiology, Social Determinants of Health, Physiology, 030204 cardiovascular system & hematology, Cohort Studies, chemistry.chemical_compound, 0302 clinical medicine, occupation, 030212 general & internal medicine, Cognitive decline, Child, Finland, life course, education, biology, 0104 Statistics, General Medicine, ALSPAC, metabolomics, 3. Good health, Docosahexaenoic acid, Metabolome, Life course approach, Educational Status, Apolipoprotein A1, lipids (amino acids, peptides, and proteins), Cohort study, Adult, medicine.medical_specialty, socio-economic status, Socio-economic status, 3121 Internal medicine, 1117 Public Health and Health Services, 03 medical and health sciences, metabonic, medicine, Humans, metabonomic, AcademicSubjects/MED00860, Risk factor, Triglycerides, Cholesterol, business.industry, lipoproteins, chemistry, biology.protein, 3111 Biomedicine, business
Abstract

Background Low socio-economic position (SEP) is a risk factor for multiple health outcomes, but its molecular imprints in the body remain unclear. Methods We examined SEP as a determinant of serum nuclear magnetic resonance metabolic profiles in ∼30 000 adults and 4000 children across 10 UK and Finnish cohort studies. Results In risk-factor-adjusted analysis of 233 metabolic measures, low educational attainment was associated with 37 measures including higher levels of triglycerides in small high-density lipoproteins (HDL) and lower levels of docosahexaenoic acid (DHA), omega-3 fatty acids, apolipoprotein A1, large and very large HDL particles (including levels of their respective lipid constituents) and cholesterol measures across different density lipoproteins. Among adults whose father worked in manual occupations, associations with apolipoprotein A1, large and very large HDL particles and HDL-2 cholesterol remained after adjustment for SEP in later life. Among manual workers, levels of glutamine were higher compared with non-manual workers. All three indicators of low SEP were associated with lower DHA, omega-3 fatty acids and HDL diameter. At all ages, children of manual workers had lower levels of DHA as a proportion of total fatty acids. Conclusions Our work indicates that social and economic factors have a measurable impact on human physiology. Lower SEP was independently associated with a generally unfavourable metabolic profile, consistent across ages and cohorts. The metabolites we found to be associated with SEP, including DHA, are known to predict cardiovascular disease and cognitive decline in later life and may contribute to health inequalities.

Published
2020

197. DNA methylation and lipid metabolism: an EWAS of 226 metabolic measures

Author

Ilkka Seppälä, John C. Chambers, Marjo-Riitta Järvelin, Thomas Meitinger, Simone Wahl, Mika Ala-Korpela, Annette Peters, Michael Roden, Martina Müller-Nurasyid, Weihua Zhang, Wolfgang Rathmann, Pamela R. Matias-Garcia, Jaspal S. Kooner, Anja Kretschmer, Holger Prokisch, Johannes Kettunen, Christian Herder, Monica del C. Gomez-Alonso, Melanie Waldenberger, Mikko Hurme, Marie Loh, Sylvain Sebert, Rory P. Wilson, Olli T. Raitakari, Liliane Pfeiffer, Ville Karhunen, Kirstin Mittelstraß, Luis R. Serrano-Garcia, Terho Lehtimäki, Sacha Horn, Christian Gieger, Tampere University, Department of Clinical Chemistry, Clinical Medicine, BioMediTech, and Lee Kong Chian School of Medicine (LKCMedicine)

Subjects
0301 basic medicine, Male, Very low-density lipoprotein, Myocardial Infarction, Blood lipids, 030204 cardiovascular system & hematology, Epigenesis, Genetic, Cohort Studies, chemistry.chemical_compound, 0302 clinical medicine, Germany, Genetics (clinical), 2. Zero hunger, Aged, 80 and over, Middle Aged, CpG site, ddc, Cpg Site, Fatty Acids, Hdl, Ldl, Lipoprotein Composition, Lipoprotein Sizes, Nmr, Obesity, Vldl, DNA methylation, Metabolome, lipids (amino acids, peptides, and proteins), Female, VLDL, Adult, medicine.medical_specialty, HDL, Biology, 3121 Internal medicine, LDL, 03 medical and health sciences, Lipoprotein composition, Lipoprotein sizes, Internal medicine, Genetics, medicine, Humans, Medicine [Science], Epigenetics, CpG Site, Fatty acids, Molecular Biology, Aged, Cholesterol, Research, Lipid metabolism, DNA Methylation, Lipid Metabolism, NMR, Myocardial infarction, 030104 developmental biology, Endocrinology, chemistry, 3111 Biomedicine, Developmental Biology, Lipoprotein, Genome-Wide Association Study
Abstract

Background The discovery of robust and trans-ethnically replicated DNA methylation markers of metabolic phenotypes, has hinted at a potential role of epigenetic mechanisms in lipid metabolism. However, DNA methylation and the lipid compositions and lipid concentrations of lipoprotein sizes have been scarcely studied. Here, we present an epigenome-wide association study (EWAS) (N = 5414 total) of mostly lipid-related metabolic measures, including a fine profiling of lipoproteins. As lipoproteins are the main players in the different stages of lipid metabolism, examination of epigenetic markers of detailed lipoprotein features might improve the diagnosis, prognosis, and treatment of metabolic disturbances. Results We conducted an EWAS of leukocyte DNA methylation and 226 metabolic measurements determined by nuclear magnetic resonance spectroscopy in the population-based KORA F4 study (N = 1662) and replicated the results in the LOLIPOP, NFBC1966, and YFS cohorts (N = 3752). Follow-up analyses in the discovery cohort included investigations into gene transcripts, metabolic-measure ratios for pathway analysis, and disease endpoints. We identified 161 associations (p value −10), covering 16 CpG sites at 11 loci and 57 metabolic measures. Identified metabolic measures were primarily medium and small lipoproteins, and fatty acids. For apolipoprotein B-containing lipoproteins, the associations mainly involved triglyceride composition and concentrations of cholesterol esters, triglycerides, free cholesterol, and phospholipids. All associations for HDL lipoproteins involved triglyceride measures only. Associated metabolic measure ratios, proxies of enzymatic activity, highlight amino acid, glucose, and lipid pathways as being potentially epigenetically implicated. Five CpG sites in four genes were associated with differential expression of transcripts in blood or adipose tissue. CpG sites in ABCG1 and PHGDH showed associations with metabolic measures, gene transcription, and metabolic measure ratios and were additionally linked to obesity or previous myocardial infarction, extending previously reported observations. Conclusion Our study provides evidence of a link between DNA methylation and the lipid compositions and lipid concentrations of different lipoprotein size subclasses, thus offering in-depth insights into well-known associations of DNA methylation with total serum lipids. The results support detailed profiling of lipid metabolism to improve the molecular understanding of dyslipidemia and related disease mechanisms.

Published
2020

198. Childhood and Adulthood Passive Smoking and Nonalcoholic Fatty Liver in Midlife: A 31-year Cohort Study

Author

Feitong Wu, Costan G. Magnussen, Johanna M. Jaakkola, Jorma S. A. Viikari, Terho Lehtimäki, Katja Pahkala, Antti Jula, Tomi T. Laitinen, Matthew A. Sabin, Suvi P. Rovio, Markus Juonala, Nina Hutri-Kähönen, and Olli T. Raitakari

Subjects
Adult, Male, Pediatrics, medicine.medical_specialty, Passive smoking, Adolescent, medicine.disease_cause, 03 medical and health sciences, 0302 clinical medicine, Non-alcoholic Fatty Liver Disease, Risk Factors, Epidemiology, medicine, Prevalence, Humans, Prospective Studies, Prospective cohort study, Child, Finland, Ultrasonography, Hepatology, business.industry, Fatty liver, Gastroenterology, Middle Aged, medicine.disease, Confidence interval, 030220 oncology & carcinogenesis, Relative risk, Child, Preschool, 030211 gastroenterology & hepatology, Female, Tobacco Smoke Pollution, business, Biomedical sciences, Cohort study
Abstract

Introduction: Identifying early life risk factors remains key to the prevention of nonalcoholic fatty liver (hereinafter "fatty liver") in adulthood. However, the longitudinal association of childhood passive smoking with adult fatty liver is not studied. We examined the association of childhood and adulthood passive smoking with fatty liver in midlife. Methods: This was a 31-year prospective cohort study of 1,315 participants. Information on childhood passive smoking (parental smoking) was collected in 1980 (aged 3-18 years) and 1983 and adulthood passive smoking in 2001, 2007, and 2011. Fatty liver was determined by ultrasound in 2011 (aged 34-49 years). Results: The prevalence of fatty liver was 16.3%. Both childhood and adulthood passive smoking were associated with higher risk of fatty liver, adjusting for potential confounders such as age, sex, childhood socioeconomic status, and adulthood physical activity and alcohol consumption (relative risk = 1.41, 95% confidence interval: 1.01-1.97 for childhood; 1.35, 1.01-1.82 for adulthood). Individuals with persistent exposure to passive smoking between childhood and adulthood had the highest risk (relative risk = 1.99, 95% confidence interval: 1.14-3.45) compared with those without passive smoking in either childhood or adulthood. Discussion: Passive smoking in both child and adult lives are associated with increased risk of adult fatty liver, suggesting that the prevention of passive smoking should start as early as possible and maintain throughout lifetime.

Published
2020

199. DNA methylation signatures of aggression and closely related constructs: A meta-analysis of epigenome-wide studies across the lifespan

Author

Katri Räikkönen, Sylvain Sebert, Marinus H. van IJzendoorn, Avshalom Caspi, Christine M. Freitag, Caroline L Relton, Geòrgia Escaramís, Barbara Franke, Kristine B. Gutzkow, Jonathan Mill, Martine Vrijheid, Eilis Hannon, Liisa Keltikangas-Järvinen, Miina Ollikainen, Karen Sugden, Sara Hägg, Josef Frank, Jordi Sunyer, Juan R. González, Jari Lahti, Archie Campbell, Juulia Jylhävä, Amaia Hervás, Aranzazu Fernandez-Rivas, Robert Vermeiren, Darina Czamara, Rosie M. Walker, Regina Grazuleviciene, Jenny van Dongen, Fabian Streit, Stewart W. Morris, Lea Sirignano, Mark Adams, Khadeeja Ismail, Rick Jansen, Marieke Klein, David L. Corcoran, Tellervo Korhonen, Silvia Alemany, Christian Hakulinen, Marian J. Bakermans-Kranenburg, Janine F. Felix, Harold Snieder, Jonathan D. Hafferty, Timo E. Strandberg, Matthew Suderman, Rosa H. Mulder, Kerstin Konrad, Peter J. Roetman, Yunzhang Wang, Louise Arseneault, Jaakko Kaprio, Marjo-Riitta Järvelin, Dennis van der Meer, Cornelis Kluft, Fiona A. Hagenbeek, Ágnes Vetró, Gareth E. Davies, Eero Vuoksimaa, Elisabeth B. Binder, Hill F. Ip, Pashupati P. Mishra, Richie Poulton, Jorunn Evandt, Henning Tiemeier, Lannie Ligthart, Terho Lehtimäki, Estelle Lowry, Meike Bartels, Mandy Meijer, Kathryn L. Evans, Leanne K. Küpers, Terrie E. Moffitt, Tabea Send, Andrew M. McIntosh, Eva Corpeleijn, Priyanka Parmar, Stephanie H. Witt, Nancy L. Pedersen, Lude Franke, Marc Jan Bonder, Dorret I. Boomsma, Olivier F. Colins, Marina Vafeiadi, Bart M. L. Baselmans, Andreas G. Chiocchetti, Michael Deuschle, and Olli T. Raitakari

Subjects
0303 health sciences, Aggression, Alpha (ethology), Physiology, Biology, medicine.disease, 03 medical and health sciences, 0302 clinical medicine, Schizophrenia, Cord blood, Meta-analysis, DNA methylation, Genetic variation, medicine, medicine.symptom, 030217 neurology & neurosurgery, 030304 developmental biology, Genetic association
Abstract

DNA methylation profiles of aggressive behavior may capture lifetime cumulative effects of genetic, stochastic, and environmental influences associated with aggression. Here, we report the first large meta-analysis of epigenome-wide association studies (EWAS) of aggressive behavior (N=15,324 participants). In peripheral blood samples of 14,434 participants from 18 cohorts with mean ages ranging from 7 to 68 years, 13 methylation sites were significantly associated with aggression (alpha=1.2×10−7; Bonferroni correction). In cord blood samples of 2,425 children from five cohorts with aggression assessed at mean ages ranging from 4 to 7 years, 83% of these sites showed the same direction of association with childhood aggression (r=0.74, p=0.006) but no epigenome-wide significant sites were found. Top-sites (48 at a false discovery rate of 5% in the peripherl blood meta-analysis or in a combined meta-analysis of peripheral blood and cord blood) have been associated with chemical exposures, smoking, cognition, metabolic traits, and genetic variation (mQTLs). Three genes whose expression levels were associated with top-sites were previously linked to schizophrenia and general risk tolerance. At six CpGs, DNA methylation variation in blood mirrors variation in the brain. On average 44% (range=3-82%) of the aggression–methylation association was explained by current and former smoking and BMI. These findings point at loci that are sensitive to chemical exposures with potential implications for neuronal functions. We hope these results to be a starting point for studies leading to applications as peripheral biomarkers and to reveal causal relationships with aggression and related traits.

Published
2020

200. Meta-analysis of 375,000 individuals identifies 38 susceptibility loci for migraine

Author

Kai-How Farh, Caleb Webber, Albert Hofman, George McMahon, Nicholas G. Martin, Paul M. Ridker, Lynn Cherkas, Mart Kals, Dorret I. Boomsma, George Davey Smith, Verneri Anttila, Tune H. Pers, Bertram Müller-Myhsok, Ville Artto, Benjamin M. Neale, Ester Cuenca-León, Anine H. Stam, Christopher Sivert Nielsen, Hieab H.H. Adams, Guntram Borck, Andres Metspalu, Maria Gudlaug Hrafnsdottir, Martin Dichgans, Reedik Mägi, Hailiang Huang, Daniel I. Chasman, Elizabeth Loehrer, John-Anker Zwart, Thomas Meitinger, Markus Färkkilä, Cornelia M. van Duijn, Arn M. J. M. van den Maagdenberg, Evie Stergiakouli, Johan G. Eriksson, Kauko Heikkilä, Hreinn Stefansson, Nicholas A. Furlotte, Minna Männikkö, Nicholas Eriksson, Jaakko Kaprio, David P. Strachan, Juho Wedenoja, Zameel M. Cader, Scott G. Gordon, Brenda W.J.H. Penninx, Linda M. Pedersen, Olli T. Raitakari, Phil Lee, André G. Uitterlinden, Ann-Louise Esserlind, Tobias Kurth, Arpo Aromaa, Priit Palta, Jes Olesen, Audun Stubhaug, Antti-Pekka Sarin, Andres Ingason, Stefan Schreiber, Salli Vepsäläinen, Hartmut Göbel, Kalle Pärn, Jouke-Jan Hottenga, Kari Stefansson, Bendik S. Winsvold, Markku Koiranen, Tim D. Spector, Evelin Mihailov, Mikko Muona, Marjo-Riitta Järvelin, Cynthia Sandor, Anne Francke Christensen, Lude Franke, Grant W. Montgomery, Tobias Freilinger, Caroline Ran, Thomas Werge, Maija Wessman, David A. Hinds, Lannie Ligthart, Terho Lehtimäki, Lili Milani, Mari A. Kaunisto, Lydia Quaye, Andrea Carmine Belin, Eija Hamalainen, M. Arfan Ikram, Veikko Salomaa, Mark J. Daly, Dale R. Nyholt, Pamela A. F. Madden, Andrew C. Heath, Tõnu Esko, Rainer Malik, Gisela M. Terwindt, Mitja I. Kurki, Aarno Palotie, Thomas Hansen, Padhraig Gormley, Michel D. Ferrari, Susan M. Ring, Julie E. Buring, Christian Kubisch, Mikko Kallela, Andrea Byrnes, Stacy Steinberg, Jie Huang, Markus Schürks, Groningen Institute for Gastro Intestinal Genetics and Immunology (3GI), Stem Cell Aging Leukemia and Lymphoma (SALL), Amsterdam Neuroscience - Complex Trait Genetics, Psychiatry, EMGO - Mental health, Internal Medicine, Epidemiology, Neurology, Amsterdam Neuroscience - Mood, Anxiety, Psychosis, Stress & Sleep, APH - Mental Health, Biological Psychology, and Complex Trait Genetics

Subjects
0301 basic medicine, Netherlands Twin Register (NTR), SMOOTH-MUSCLE-CELLS, Medizin, Genome-wide association study, Disease, Bioinformatics, Genome-wide association studies, 0302 clinical medicine, Familial hemiplegic migraine, GENE-EXPRESSION, Genetics, Genetics & Heredity, FAMILIAL HEMIPLEGIC MIGRAINE, International Headache Genetics Consortium, SINGLE-NUCLEOTIDE POLYMORPHISMS, 11 Medical And Health Sciences, Genomics, SDG 10 - Reduced Inequalities, 3. Good health, Migranya, Cortical spreading depression, SPREADING DEPRESSION, Life Sciences & Biomedicine, Gens, Genetic Markers, Migraine Disorders, Locus (genetics), Single-nucleotide polymorphism, Biology, GENOTYPE IMPUTATION, Polymorphism, Single Nucleotide, 03 medical and health sciences, medicine, SYSTEMATIC ANALYSIS, Humans, Genetic Predisposition to Disease, Vascular Diseases, GENOME-WIDE ASSOCIATION, Migraine, Science & Technology, Case-control study, Muscle, Smooth, 06 Biological Sciences, medicine.disease, 030104 developmental biology, Genes, MYOCARDIAL-INFARCTION, Genetic Loci, Case-Control Studies, RECEPTOR-RELATED PROTEIN-1, 030217 neurology & neurosurgery, Developmental Biology, Genome-Wide Association Study
Abstract

Migraine is a debilitating neurological disorder affecting around one in seven people worldwide, but its molecular mechanisms remain poorly understood. There is some debate about whether migraine is a disease of vascular dysfunction or a result of neuronal dysfunction with secondary vascular changes. Genome-wide association ( GWA) studies have thus far identified 13 independent loci associated with migraine. To identify new susceptibility loci, we carried out a genetic study of migraine on 59,674 affected subjects and 316,078 controls from 22 GWA studies. We identified 44 independent single-nucleotide polymorphisms ( SNPs) significantly associated with migraine risk ( P

Published
2020

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