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1. Adipocyte deletion of the oxygen-sensor PHD2 sustains elevated energy expenditure at thermoneutrality

Author: Rongling Wang, Mario Gomez Salazar, Iris Pruñonosa Cervera, Amanda Coutts, Karen French, Marlene Magalhaes Pinto, Sabrina Gohlke, Ruben García-Martín, Matthias Blüher, Christopher J. Schofield, Ioannis Kourtzelis, Roland H. Stimson, Cécile Bénézech, Mark Christian, Tim J. Schulz, Elias F. Gudmundsson, Lori L. Jennings, Vilmundur G. Gudnason, Triantafyllos Chavakis, Nicholas M. Morton, Valur Emilsson, and Zoi Michailidou
Subjects: Science
Abstract: Abstract Enhancing thermogenic brown adipose tissue (BAT) function is a promising therapeutic strategy for metabolic disease. However, predominantly thermoneutral modern human living conditions deactivate BAT. We demonstrate that selective adipocyte deficiency of the oxygen-sensor HIF-prolyl hydroxylase (PHD2) gene overcomes BAT dormancy at thermoneutrality. Adipocyte-PHD2-deficient mice maintain higher energy expenditure having greater BAT thermogenic capacity. In human and murine adipocytes, a PHD inhibitor increases Ucp1 levels. In murine brown adipocytes, antagonising the major PHD2 target, hypoxia-inducible factor-(HIF)−2a abolishes Ucp1 that cannot be rescued by PHD inhibition. Mechanistically, PHD2 deficiency leads to HIF2 stabilisation and binding of HIF2 to the Ucp1 promoter, thus enhancing its expression in brown adipocytes. Serum proteomics analysis of 5457 participants in the deeply phenotyped Age, Gene and Environment Study reveal that serum PHD2 associates with increased risk of metabolic disease. Here we show that adipose-PHD2-inhibition is a therapeutic strategy for metabolic disease and identify serum PHD2 as a disease biomarker.
Published: 2024
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2. A proteogenomic signature of age-related macular degeneration in blood

Author: Valur Emilsson, Elias F. Gudmundsson, Thorarinn Jonmundsson, Brynjolfur G. Jonsson, Michael Twarog, Valborg Gudmundsdottir, Zhiguang Li, Nancy Finkel, Stephen Poor, Xin Liu, Robert Esterberg, Yiyun Zhang, Sandra Jose, Chia-Ling Huang, Sha-Mei Liao, Joseph Loureiro, Qin Zhang, Cynthia L. Grosskreutz, Andrew A. Nguyen, Qian Huang, Barrett Leehy, Rebecca Pitts, Thor Aspelund, John R. Lamb, Fridbert Jonasson, Lenore J. Launer, Mary Frances Cotch, Lori L. Jennings, Vilmundur Gudnason, and Tony E. Walshe
Subjects: Science
Abstract: Age related macular degeneration is a common cause of visual impairment in the elderly, but the etiology is not fully understood. Here, the authors use genetic data, serum proteomics, and AMD phenotypic data from a large Icelandic cohort to discover proteins altered in, causally related to AMD or signifying progression of advanced AMD.
Published: 2022
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3. A genome-wide association study of serum proteins reveals shared loci with common diseases

Author: Alexander Gudjonsson, Valborg Gudmundsdottir, Gisli T. Axelsson, Elias F. Gudmundsson, Brynjolfur G. Jonsson, Lenore J. Launer, John R. Lamb, Lori L. Jennings, Thor Aspelund, Valur Emilsson, and Vilmundur Gudnason
Subjects: Science
Abstract: Circulating proteins have been linked to many conditions, and understanding their genetic control can lead to understanding of disease. Here, the authors associate common genetic variants with protein levels, finding overlap of genetic associations with circulating proteins and complex disease.
Published: 2022
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4. Coding and regulatory variants are associated with serum protein levels and disease

Author: Valur Emilsson, Valborg Gudmundsdottir, Alexander Gudjonsson, Thorarinn Jonmundsson, Brynjolfur G. Jonsson, Mohd A. Karim, Marjan Ilkov, James R. Staley, Elias F. Gudmundsson, Lenore J. Launer, Jan H. Lindeman, Nicholas M. Morton, Thor Aspelund, John R. Lamb, Lori L. Jennings, and Vilmundur Gudnason
Subjects: Science
Abstract: Finding the genetic basis of protein expression can elucidate the genetic mechanisms of disease. Here, the authors link low-frequency and common DNA sequence variants to thousands of serum proteins, finding genetic overlap between circulating proteins and a wide range of common diseases.
Published: 2022
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5. Serum levels of ACE2 are higher in patients with obesity and diabetes

Author: Valur Emilsson, Elias F. Gudmundsson, Thor Aspelund, Brynjolfur G. Jonsson, Alexander Gudjonsson, Lenore J. Launer, John R. Lamb, Valborg Gudmundsdottir, Lori L. Jennings, and Vilmundur Gudnason
Subjects: Internal medicine, RC31-1245
Abstract: Abstract Objective As severity of outcome in COVID‐19 is disproportionately higher among individuals with obesity, smokers, patients with hypertension, kidney disease, chronic pulmonary disease, coronary heart disease (CHD), and/or type 2 diabetes (T2D), serum levels of ACE2, the cellular entry point for the coronavirus SARS‐CoV‐2, were examined in these high‐risk groups. Methods Associations of ACE2 levels to smokers and patients with hypertension, T2D, obesity, CHD, or COPD were investigated in a single center population‐based study of 5457 Icelanders from the Age, Gene/Environment Susceptibility Reykjavík Study (AGES‐RS) of the elderly (mean age 75 ± 6 years), using multiple linear regression analysis. Results Serum levels of ACE2 were higher in smokers and individuals with T2D and/or obesity while they were unaffected in the other patient groups. Conclusion ACE2 levels are higher in some patient groups with comorbidities linked to COVID‐19 including obesity and T2D and as such may have an emerging role as a circulating biomarker for severity of outcome in the disease.
Published: 2021
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6. Progression of traction bronchiectasis/bronchiolectasis in interstitial lung abnormalities is associated with increased all-cause mortality: Age Gene/Environment Susceptibility-Reykjavik Study

Author: Takuya Hino, Tomoyuki Hida, Mizuki Nishino, Junwei Lu, Rachel K. Putman, Elias F. Gudmundsson, Akinori Hata, Tetsuro Araki, Vladimir I. Valtchinov, Osamu Honda, Masahiro Yanagawa, Yoshitake Yamada, Takeshi Kamitani, Masahiro Jinzaki, Noriyuki Tomiyama, Kousei Ishigami, Hiroshi Honda, Raul San Jose Estepar, George R. Washko, Takeshi Johkoh, David C. Christiani, David A. Lynch, Vilmundur Gudnason, Gunnar Gudmundsson, Gary M. Hunninghake, and Hiroto Hatabu
Subjects: Interstitial lung abnormality, Usual interstitial pneumonia, Pulmonary fibrosis, Traction bronchiectasis, Age Gene/Environment Susceptibility-Reykjavik Study, Medical physics. Medical radiology. Nuclear medicine, R895-920
Abstract: Purpose: The aim of this study is to assess the role of traction bronchiectasis/bronchiolectasis and its progression as a predictor for early fibrosis in interstitial lung abnormalities (ILA). Methods: Three hundred twenty-seven ILA participants out of 5764 in the Age, Gene/Environment Susceptibility (AGES)-Reykjavik Study who had undergone chest CT twice with an interval of approximately five-years were enrolled in this study. Traction bronchiectasis/bronchiolectasis index (TBI) was classified on a four-point scale: 0, ILA without traction bronchiectasis/bronchiolectasis; 1, ILA with bronchiolectasis but without bronchiectasis or architectural distortion; 2, ILA with mild to moderate traction bronchiectasis; 3, ILA and severe traction bronchiectasis and/or honeycombing. Traction bronchiectasis (TB) progression was classified on a five-point scale: 1, Improved; 2, Probably improved; 3, No change; 4, Probably progressed; 5, Progressed. Overall survival (OS) among participants with different TB Progression Score and between the TB progression group and No TB progression group was also investigated. Hazard radio (HR) was estimated with Cox proportional hazards model. Results: The higher the TBI at baseline, the higher TB Progression Score (P
Published: 2021
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7. Effect of Genetically Low 25-Hydroxyvitamin D on Mortality Risk: Mendelian Randomization Analysis in 3 Large European Cohorts

Author: Thor Aspelund, Martin R. Grübler, Albert V. Smith, Elias F. Gudmundsson, Martin Keppel, Mary Frances Cotch, Tamara B. Harris, Rolf Jorde, Guri Grimnes, Ragnar Joakimsen, Henrik Schirmer, Tom Wilsgaard, Ellisiv B. Mathiesen, Inger Njølstad, Maja-Lisa Løchen, Winfried März, Marcus E. Kleber, Andreas Tomaschitz, Diana Grove-Laugesen, Lars Rejnmark, Karin M. A. Swart, Ingeborg A. Brouwer, Paul Lips, Natasja M. van Schoor, Christopher T. Sempos, Ramón A. Durazo-Arvizu, Zuzana Škrabáková, Kirsten G. Dowling, Kevin D. Cashman, Mairead Kiely, Stefan Pilz, Vilmundur Gudnason, and Gudny Eiriksdottir
Subjects: Vitamin D, standardized 25(OH)D, Mendelian randomization, mortality, cohorts, Individual Participant Data, Nutrition. Foods and food supply, TX341-641
Abstract: The aim of this study was to determine if increased mortality associated with low levels of serum 25-hydroxyvitamin D (25(OH)D) reflects a causal relationship by using a Mendelian randomisation (MR) approach with genetic variants in the vitamin D synthesis pathway. Individual participant data from three European cohorts were harmonized with standardization of 25(OH)D according to the Vitamin D Standardization Program. Most relevant single nucleotide polymorphisms of the genes CYP2R1 (rs12794714, rs10741657) and DHCR7/NADSYN1 (rs12785878, rs11234027), were combined in two allelic scores. Cox proportional hazards regression models were used with the ratio estimator and the delta method for calculating the hazards ratio (HR) and standard error of genetically determined 25(OH)D effect on all-cause mortality. We included 10,501 participants (50.1% females, 67.1±10.1 years) of whom 4003 died during a median follow-up of 10.4 years. The observed adjusted HR for all-cause mortality per decrease in 25(OH)D by 20 nmol/L was 1.20 (95% CI: 1.15–1.25). The HR per 20 nmol/L decrease in genetically determined 25(OH)D was 1.32 (95% CI: 0.80–2.24) and 1.35 (95% CI of 0.81 to 2.37) based on the two scores. In conclusion, the results of this MR study in a combined sample from three European cohort studies provide further support for a causal relationship between vitamin D deficiency and increased all-cause mortality. However, as the current study, even with ~10,000 participants, was underpowered for the study of the effect of the allele score on mortality, larger studies on genetics and mortality are needed to improve the precision.
Published: 2019
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8. The Proteomic Profile of Interstitial Lung Abnormalities

Author: Gisli Thor Axelsson, Gunnar Gudmundsson, Katherine A. Pratte, Thor Aspelund, Rachel K. Putman, Jason L. Sanders, Elias F. Gudmundsson, Hiroto Hatabu, Valborg Gudmundsdottir, Alexander Gudjonsson, Takuya Hino, Tomoyuki Hida, Brian D. Hobbs, Michael H. Cho, Edwin K. Silverman, Russell P. Bowler, Lenore J. Launer, Lori L. Jennings, Gary M. Hunninghake, Valur Emilsson, and Vilmundur Gudnason
Subjects: Proteomics, Pulmonary and Respiratory Medicine, Humans, Genetic Predisposition to Disease, Prospective Studies, Respiratory System Abnormalities, Lung Diseases, Interstitial, Tomography, X-Ray Computed, Critical Care and Intensive Care Medicine, Lung
Published: 2022

9. Abstract P519: Reduced Liver Fat and Improved Cardiometabolic Health in Individuals With Non Alcoholic Fatty Liver Disease After a 12 Week Digital Intervention - A Feasibility Study

Author: Sigridur Bjornsdottir, Hildigunnur Ulfsdottir, Elias F Gudmundsson, Kolbrun Sveinsdottir, Ari P Isberg, Gudlaug Bjornsdottir, Sigurdur Sigurdsson, Saemundur Oddsson, and Vilmundur Gudnason
Subjects: Physiology (medical), Cardiology and Cardiovascular Medicine
Abstract: Introduction: Cardiovascular disease is the most common cause of death among people with non-alcoholic fatty liver disease (NAFLD) and lifestyle changes can improve health outcomes. A NAFLD digital intervention was designed and here we report retention, engagement and satisfaction results in addition to the program's potential clinical impact on markers of liver- and cardiometabolic health. Hypothesis: We assessed the hypothesis that a digital intervention is feasible for individuals with metabolic derangements and NAFLD to improve cardiometabolic health. Methods: A prospective, open label, single arm, 12 week long study was conducted in Iceland.The intervention was delivered through the Sidekick app, with focus on disease education, low carbohydrate diet, increasing activity levels, reducing stress and healthy lifestyle coaching. Individuals with either BMI>30, metabolic syndrome or type 2 diabetes were screened for NAFLD with a FibroScan assessment. Other potential reasons for liver steatosis were excluded. Following recruitment and collection of demographic data, anthropometric and clinical measurements, MRI-PDFF for liver fat content, dual-energy X-ray absorptiometry for body composition and blood tests, were carried out at baseline and after 12 weeks. Primary outcomes were engagement and retention as measured in-app, and user satisfaction (mHealth App Usability Questionnaire); secondary outcomes were changes in weight, liver fat content and other cardiovascular risk factors. Results: In total, 38 individuals were included in the study and 34 (89%) completed the program (defined as being active 9/12 weeks). The median age was 59.5 [IQR 46.0,69.0] years and 23 (60.5%) were females. The median number of active days was 81 [IQR 45.8, 84.0] and the median user satisfaction score was 6.3 out of 7. The mean weight loss was 3.5 kg (SD=3.7) (p Conclusion: This study suggests that a holistic digital intervention may improve liver-specific and cardiometabolic health in individuals with NAFLD, as indicated by the reduction in liver fat, systolic blood pressure and improvements in body composition. Together with the excellent program engagement, completion and satisfaction, this approach could provide a new tool to improve health outcomes in NAFLD.
Published: 2023

10. Serum levels of ACE2 are higher in patients with obesity and diabetes

Author: Vilmundur Gudnason, John Lamb, Alexander Gudjonsson, Elias F. Gudmundsson, Thor Aspelund, Valur Emilsson, Lenore J. Launer, Brynjolfur G. Jonsson, Valborg Gudmundsdottir, and Lori L. Jennings
Subjects: 0301 basic medicine, lcsh:Internal medicine, medicine.medical_specialty, Short Communication, Endocrinology, Diabetes and Metabolism, Population, 030209 endocrinology & metabolism, Type 2 diabetes, Disease, Single Center, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, Diabetes mellitus, medicine, lcsh:RC31-1245, education, COPD, education.field_of_study, 030109 nutrition & dietetics, Nutrition and Dietetics, business.industry, medicine.disease, Obesity, business, Kidney disease
Abstract: Objective As severity of outcome in COVID‐19 is disproportionately higher among individuals with obesity, smokers, patients with hypertension, kidney disease, chronic pulmonary disease, coronary heart disease (CHD), and/or type 2 diabetes (T2D), serum levels of ACE2, the cellular entry point for the coronavirus SARS‐CoV‐2, were examined in these high‐risk groups. Methods Associations of ACE2 levels to smokers and patients with hypertension, T2D, obesity, CHD, or COPD were investigated in a single center population‐based study of 5457 Icelanders from the Age, Gene/Environment Susceptibility Reykjavík Study (AGES‐RS) of the elderly (mean age 75 ± 6 years), using multiple linear regression analysis. Results Serum levels of ACE2 were higher in smokers and individuals with T2D and/or obesity while they were unaffected in the other patient groups. Conclusion ACE2 levels are higher in some patient groups with comorbidities linked to COVID‐19 including obesity and T2D and as such may have an emerging role as a circulating biomarker for severity of outcome in the disease.
Published: 2020

11. Cerebrovascular risk-factors of prevalent and incident brain Infarcts in the general population

Author: Sigurdur Sigurdsson, Vilmundur Gudnason, Elias F. Gudmundsson, Lenore J. Launer, Olafur Kjartansson, Palmi V. Jonsson, Thor Aspelund, and Mark A. van Buchem
Subjects: medicine.medical_specialty, hypertension, Migraine Disorders, Population, Article, Internal medicine, medicine, Humans, magnetic resonance imaging, risk factors, atrial fibrillation, cardiovascular diseases, brain infarction, education, Cerebrovascular risk, Aged, Advanced and Specialized Nursing, education.field_of_study, medicine.diagnostic_test, business.industry, Brain, blood pressure, Magnetic resonance imaging, Atrial fibrillation, Cerebral Infarction, medicine.disease, Blood pressure, Brain infarction, Cardiology, Neurology (clinical), Cardiology and Cardiovascular Medicine, business
Abstract: Background: Studies on the association of cerebrovascular risk factors to magnetic resonance imaging detected brain infarcts have been inconsistent, partly reflecting limits of assessment to infarcts anywhere in the brain, as opposed to specific brain regions. We hypothesized that risk-factors may differ depending on where the infarct is located in subcortical-, cortical-, and cerebellar regions. Methods: Participants (n=2662, mean age 74.6±4.8) from the longitudinal population-based AGES (Age, Gene/Environment Susceptibility)-Reykjavik Study underwent brain magnetic resonance imaging at baseline and on average 5.2 years later. We assessed the number and location of brain infarcts (prevalent versus incident). We estimated the risk-ratios of prevalent (PRR) and incident (IRR) infarcts by baseline cerebrovascular risk-factors using Poisson regression. Results: Thirty-one percent of the study participants had prevalent brain infarcts and 21% developed new infarcts over 5 years. Prevalent subcortical infarcts were associated with hypertension (PRR, 2.7 [95% CI, 1.1–6.8]), systolic blood pressure (PRR, 1.2 [95% CI, 1.1–1.4]), and diabetes (PRR, 2.8 [95% CI, 1.9–4.1]); incident subcortical infarcts were associated with systolic (IRR, 1.2 [95% CI, 1.0–1.4]) and diastolic (IRR, 1.3 [95% CI, 1.0–1.6]) blood pressure. Prevalent and incident cortical infarcts were associated with carotid plaques (PRR, 1.8 [95% CI, 1.3–2.5] and IRR, 1.9 [95% CI, 1.3–2.9], respectively), and atrial fibrillation was significantly associated with prevalent cortical infarcts (PRR, 1.8 [95% CI, 1.2–2.7]). Risk-factors for prevalent cerebellar infarcts included hypertension (PRR, 2.45 [95% CI, 1.5–4.0]), carotid plaques (PRR, 1.45 [95% CI, 1.2–1.8]), and migraine with aura (PRR, 1.6 [95% CI, 1.1–2.2]). Incident cerebellar infarcts were only associated with any migraine (IRR, 1.4 [95% CI, 1.0–2.0]). Conclusions: The risk for subcortical infarcts tends to increase with small vessel disease risk-factors such as hypertension and diabetes. Risk for cortical infarcts tends to increase with atherosclerotic/coronary processes and risk for cerebellar infarcts with a more mixed profile of factors. Assessment of risk-factors by location of asymptomatic infarcts found on magnetic resonance imaging may improve the ability to target and optimize preventive therapeutic approaches to prevent stroke.
Published: 2022

12. Abstract P049: A Digital Therapeutic Intervention Is Feasible For Outpatient Care In Coronary Artery Disease

Author: David O Arnar, Saemundur Oddsson, Thrudur Gunnarsdottir, Inga V Olafsdottir, Maria V Gudmundsdottir, Kjartan H Loftsson, Elias F Gudmundsson, Bylgja Kaernested, Maria L Amundadottir, Svala Sigurdardottir, Brynjolfur Mogensen, Berglind Libungan, and Tryggvi Thorgeirsson
Subjects: Physiology (medical), Cardiology and Cardiovascular Medicine
Abstract: Introduction: Lifestyle and medication adherence are important factors in secondary coronary artery disease (CAD)-prevention. Furthermore, the mind-heart-body connection is gaining recognition in cardiovascular health management. Hypothesis: We assessed the hypothesis that a CAD-specific digital intervention is feasible for outpatient care in terms of program retention, satisfaction, quality of life, symptom frequency and medication adherence. Methods: A four-week CAD-program (SK-121) delivered via a smart phone was designed in collaboration between the National University Hospital of Iceland (NUHI) and Sidekick Health. Patient recruitment took place at NUHI, and program participation consisted of daily health promoting missions assigned within the digital intervention such as watching educational videos, mindfulness exercises, medication reminders and logging quality of life scores. Pre- and post-intervention questionnaires were administered for the Hospital anxiety and depression scale (HADS), Seattle Angina Questionnaire-7 (SAQ-7) and the Morisky medication adherence scale (MMAS-8). Stress-, energy-levels and quality of sleep were logged on a ten-point scale. Participants were interviewed about their program experience. Results: A total of 33 individuals signed informed consent and completed the baseline survey, of which 25 individuals registered in the app (76% males, mean age 60 years [SD=10]). A total of 23 participants logged a mission during the 4-week intervention, five of those were active a single day. A total of 16 (70%) participants completed the program and both pre- and post-surveys (mean age 60 years [SD=10], range 44-80 years). On average participants logged 7.5 missions/day (10.2 for women and 6.6 for men), completing half of daily missions (women 71%, men 47%). Results for average quality of life scores from week one to four were: for energy 5.5[SD=1.8] to 5.8[SD=1.9], p =0.22, for quality of sleep 6.2[SD=2.5] to 5.9[SD=2.4] p =0.20 and for stress 3.3[SD=2.6] to 3.3[SD=2.4] p =0.71.The proportion of the 16 patients who experienced CAD-symptoms in the last four weeks decreased from 56% at baseline to 38% at program completion, p p =0.03.There were slight non-significant decreases in anxiety scores from 4.3 [SD=3.4] to 4.13[SD=2.9] p =0.88 and depression scores from 3.1 [SD=3.3] to 2.8[SD=3.6] p =0.33.User satisfaction was good as 75% of the 16 participants said it was likely that they would recommend the program, that it had a positive effect on their life, well-being and ability to deal with their disease. Conclusions: In conclusion, a CAD-specific digital intervention is feasible in terms of engagement, user satisfaction and improved treatment adherence. An RCT study is being planned to further test the program.
Published: 2022

13. Associations of ω-3 Fatty Acids With Interstitial Lung Disease and Lung Imaging Abnormalities Among Adults

Author: Gunnar Gudmundsson, Brian T. Steffen, Steven M. Kawut, Josée Dupuis, Elias F Gudmundsson, Michael Y. Tsai, Hanfei Xu, Eric A. Hoffman, Vilmundur Gudnason, Ganesh Raghu, John S. Kim, George T. O'Connor, David J. Lederer, Gary M. Hunninghake, Imre Noth, Erin D. Michos, Rachel A. Murphy, Gisli Thor Axelsson, R. Graham Barr, William S. Harris, Anna J. Podolanczuk, and Ramachandran S. Vasan
Subjects: Male, medicine.medical_specialty, Epidemiology, Population, Lower risk, Gastroenterology, 03 medical and health sciences, 0302 clinical medicine, Framingham Heart Study, Risk Factors, Internal medicine, Fatty Acids, Omega-3, medicine, Humans, 030212 general & internal medicine, education, Aged, Aged, 80 and over, chemistry.chemical_classification, education.field_of_study, business.industry, Hazard ratio, Interstitial lung disease, Original Contribution, Odds ratio, Middle Aged, medicine.disease, Hospitalization, Epidemiologic Studies, Cross-Sectional Studies, 030228 respiratory system, chemistry, Docosahexaenoic acid, Fatty Acids, Unsaturated, Female, Lung Diseases, Interstitial, Tomography, X-Ray Computed, business, Polyunsaturated fatty acid
Abstract: Docosahexaenoic acid (DHA), an ω-3 polyunsaturated fatty acid, attenuates interstitial lung disease (ILD) in experimental models, but human studies are lacking. We examined associations of circulating levels of DHA and other polyunsaturated fatty acids with hospitalization and death due to ILD over 12 years in the Multi-Ethnic Study of Atherosclerosis (MESA; n = 6,573). We examined cross-sectional associations with CT lung abnormalities in MESA (2000–2012; n = 6,541), the Framingham Heart Study (2005–2011; n = 3,917), and the Age, Gene/Environment Susceptibility-Reykjavik Study (AGES-Reykjavik) (2002–2006; n = 1,106). Polyunsaturated fatty acid levels were determined from fasting blood samples and extracted from plasma phospholipids (MESA and AGES-Reykjavik) or red blood cell membranes (Framingham Heart Study). Higher DHA levels were associated with a lower risk of hospitalization due to ILD (per standard-deviation increment, adjusted rate ratio = 0.69, 95% confidence interval (CI): 0.48, 0.99) and a lower rate of death due to ILD (per standard-deviation increment, adjusted hazard ratio = 0.68, 95% CI: 0.47, 0.98). Higher DHA was associated with fewer interstitial lung abnormalities on computed tomography (per natural log increment, pooled adjusted odds ratio = 0.65, 95% CI: 0.46, 0.91). Higher DHA levels were associated with a lower risk of hospitalization and death due to ILD and fewer lung abnormalities on computed tomography in a meta-analysis of data from population-based cohort studies.
Published: 2020

14. Associations of Pulmonary Function with MRI Brain Volumes: A Coordinated Multi-Study Analysis

Author: Stefan Frenzel, Joshua C. Bis, Elias F. Gudmundsson, Adrienne O’Donnell, Jeannette Simino, Amber Yaqub, Traci M. Bartz, Guy G. O. Brusselle, Robin Bülow, Charles S. DeCarli, Ralf Ewert, Sina A. Gharib, Saptaparni Ghosh, Monica Gireud-Goss, Rebecca F. Gottesman, M. Arfan Ikram, David S. Knopman, Lenore J. Launer, Stephanie J. London, W.T. Longstreth, Oscar L. Lopez, Debora Melo van Lent, George O’Connor, Claudia L. Satizabal, Srishti Shrestha, Sigurdur Sigurdsson, Beate Stubbe, Rajesh Talluri, Ramachandran S. Vasan, Meike W. Vernooij, Henry Völzke, Kerri L. Wiggins, Bing Yu, Alexa S. Beiser, Vilmundur Gudnason, Thomas Mosley, Bruce M. Psaty, Frank J. Wolters, Hans J. Grabe, Sudha Seshadri, Epidemiology, Pulmonary Medicine, and Radiology & Nuclear Medicine
Subjects: Aging, Clinical Sciences, Article, SDG 3 - Good Health and Well-being, Clinical Research, Forced Expiratory Volume, Medicine and Health Sciences, Humans, ddc:610, diagnostic imaging [Brain], Lung, Aged, Neurology & Neurosurgery, General Neuroscience, respiratory function tests, Neurosciences, Brain, General Medicine, diagnostic imaging [Lung], Magnetic Resonance Imaging, Brain Disorders, Psychiatry and Mental health, Clinical Psychology, Cross-Sectional Studies, Dementia, epidemiology, Cognitive Sciences, Geriatrics and Gerontology
Abstract: Background: Previous studies suggest poor pulmonary function is associated with increased burden of cerebral white matter hyperintensities and brain atrophy among elderly individuals, but the results are inconsistent. Objective: To study the cross-sectional associations of pulmonary function with structural brain variables. Methods: Data from six large community-based samples (N = 11,091) were analyzed. Spirometric measurements were standardized with respect to age, sex, height, and ethnicity using reference equations of the Global Lung Function Initiative. Associations of forced expiratory volume in 1 second (FEV1), forced vital capacity (FVC), and their ratio FEV1/FVC with brain volume, gray matter volume, hippocampal volume, and volume of white matter hyperintensities were investigated using multivariable linear regressions for each study separately and then combined using random-effect meta-analyses. Results: FEV1 and FVC were positively associated with brain volume, gray matter volume, and hippocampal volume, and negatively associated with white matter hyperintensities volume after multiple testing correction, with little heterogeneity present between the studies. For instance, an increase of FVC by one unit was associated with 3.5 ml higher brain volume (95% CI: [2.2, 4.9]). In contrast, results for FEV1/FVC were more heterogeneous across studies, with significant positive associations with brain volume, gray matter volume, and hippocampal volume, but not white matter hyperintensities volume. Associations of brain variables with both FEV1 and FVC were consistently stronger than with FEV1/FVC, specifically with brain volume and white matter hyperintensities volume. Conclusion: In cross-sectional analyses, worse pulmonary function is associated with smaller brain volumes and higher white matter hyperintensities burden.
Published: 2022

15. 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. 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Casajús, Guang Ning, Lutgart Braeckman, Dirk Vanderschueren, Jochanan Stessman, Ivana Radic, Yi Zeng, Hans Concin, Damaskini Valvi, Sari Hantunen, Catherine Kyobutungi, Diego Augusto Santos Silva, Wenhua Zhao, Sok King Ong, Anne W. Taylor, Iraj Nabipour, Justyna Godos, Cyrus Cooper, Mattias Johansson, Samuel C. Dumith, Magdalena Muc, Sabine Schipf, Idowu O Senbanjo, Jim Mann, Rajaa Al-Raddadi, Yih Chung Tham, Kay-Tee Khaw, Joseph Cacciottolo, Ana Henriques, Sahar Saeedi Moghaddam, Reza Mohammadpourhodki, 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, Camilla T. Damsgaard, Takafumi Ishida, Ekaterina Chikova-Iscener, Mirjam M. Heinen, Tazeen H. Jafar, Semánová Csilla, Constance Schultsz, Santiago F. Gomez, Raija Korpelainen, Edward W. Gregg, Laura Gutierrez, Pierre Traissac, Victor M. Herrera, Aristides M. 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. 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Ltd, Orebro University, University of London, Universitas Indonesia, Institute of Food and Nutrition Development of Ministry of Agriculture and Rural Affairs, Children’s Hospital of Fudan University, University of Cyprus, Niigata University, International Medical University, Iran University of Medical Sciences, Center for Diabetes and Endocrine Care, Peking University First Hospital, Jiangsu Provincial Center for Disease Control and Prevention, Sun Yat-sen University, West Kazakhstan Medical University, Inner Mongolia Medical University, University of Ghana, Maria Lc Iurilli , Bin Zhou , James E Bennett , Rodrigo M Carrillo-Larco , Marisa K Sophiea , Andrea Rodriguez-Martinez , Honor Bixby , Bethlehem D Solomon , Cristina Taddei , Goodarz Danaei , Mariachiara Di Cesare , Gretchen A Stevens , Leanne M Riley , Stefan Savin , Melanie J Cowan , Pascal Bovet , Albertino Damasceno , Adela Chirita-Emandi , Alison J Hayes , Nayu Ikeda , Rod T Jackson , Young-Ho Khang , Avula Laxmaiah , Jing Liu , J Jaime Miranda , Olfa Saidi , Sylvain Sebert , Maroje Sorić , Gregor Starc , Edward W Gregg , Leandra Abarca-Gómez , Ziad A Abdeen , Shynar Abdrakhmanova , Suhaila Abdul Ghaffar , Hanan F Abdul Rahim , Niveen M Abu-Rmeileh , Jamila Abubakar Garba , Benjamin Acosta-Cazares , Robert J Adams , Wichai Aekplakorn , Kaosar Afsana , Shoaib Afzal , Imelda A Agdeppa , Javad Aghazadeh-Attari , Carlos A Aguilar-Salinas , Charles Agyemang , Mohamad Hasnan Ahmad , Noor Ani Ahmad , Ali Ahmadi , Naser Ahmadi , Soheir H Ahmed , Wolfgang Ahrens , Gulmira Aitmurzaeva , Kamel Ajlouni , Hazzaa M Al-Hazzaa , Badreya Al-Lahou , Rajaa Al-Raddadi , Monira Alarouj , Fadia AlBuhairan , Shahla AlDhukair , Mohamed M Ali , Abdullah Alkandari , Ala'a Alkerwi , Kristine Allin , Mar Alvarez-Pedrerol , Eman Aly , Deepak N Amarapurkar , Parisa Amiri , Norbert Amougou , Philippe Amouyel , Lars Bo Andersen , Sigmund A Anderssen , Lars Ängquist , Ranjit Mohan Anjana , Alireza Ansari-Moghaddam , Hajer Aounallah-Skhiri , Joana Araújo , Inger Ariansen , Tahir Aris , Raphael E Arku , Nimmathota Arlappa , Krishna K Aryal , Thor Aspelund , Felix K Assah , Maria Cecília F Assunção , May Soe Aung , Juha Auvinen , Mária Avdicová , Shina Avi , Ana Azevedo , Mohsen Azimi-Nezhad , Fereidoun Azizi , Mehrdad Azmin , Bontha V Babu , Maja Bæksgaard Jørgensen , Azli Baharudin , Suhad Bahijri , Jennifer L Baker , Nagalla Balakrishna , Mohamed Bamoshmoosh , Maciej Banach , Piotr Bandosz , José R Banegas , Joanna Baran , Barbagallo CM, Alberto Barceló , Amina Barkat , Aluisio Jd Barros , Mauro Virgílio Gomes Barros , Abdul Basit , Joao Luiz D Bastos , Iqbal Bata , Anwar M Batieha , Rosangela L Batista , Zhamilya Battakova , Assembekov Batyrbek , Louise A Baur , Robert Beaglehole , Silvia Bel-Serrat , Antonisamy Belavendra , Habiba Ben Romdhane , Judith Benedics , Mikhail Benet , Ingunn Holden Bergh , Salim Berkinbayev , Antonio Bernabe-Ortiz , Gailute Bernotiene , Heloísa Bettiol , Jorge Bezerra , Aroor Bhagyalaxmi , Sumit Bharadwaj , Santosh K Bhargava , Zulfiqar A Bhutta , Hongsheng Bi , Yufang Bi , Daniel Bia , Elysée Claude Bika Lele, Mukharram M Bikbov , Bihungum Bista , Dusko J Bjelica , Peter Bjerregaard , Espen Bjertness , Marius B Bjertness , Cecilia Björkelund , Katia V Bloch , Anneke Blokstra , Simona Bo , Martin Bobak , Lynne M Boddy , Bernhard O Boehm , Heiner Boeing , Jose G Boggia , Elena Bogova , Carlos P Boissonnet , Stig E Bojesen , Marialaura Bonaccio , Vanina Bongard , Alice Bonilla-Vargas , Matthias Bopp , Herman Borghs , Lien Braeckevelt , Lutgart Braeckman , Marjolijn Ce Bragt , Imperia Brajkovich , Francesco Branca , Juergen Breckenkamp , João Breda , Hermann Brenner , Lizzy M Brewster , Garry R Brian , Lacramioara Brinduse , Sinead Brophy , Graziella Bruno , H Bas Bueno-de-Mesquita , Anna Bugge , Marta Buoncristiano , Genc Burazeri , Con Burns , Antonio Cabrera de León , Joseph Cacciottolo , Hui Cai , Tilema Cama , Christine Cameron , José Camolas , Günay Can , Ana Paula C Cândido , Felicia Cañete , Mario V Capanzana , Nadežda Capková , Eduardo Capuano , Vincenzo Capuano , Marloes Cardol , Viviane C Cardoso , Axel C Carlsson , Esteban Carmuega , Joana Carvalho , José A Casajús , Felipe F Casanueva , Ertugrul Celikcan , Laura Censi , Marvin Cervantes-Loaiza , Juraci A Cesar , Snehalatha Chamukuttan , Angelique W Chan , Queenie Chan , Himanshu K Chaturvedi , Nish Chaturvedi , Norsyamlina Che Abdul Rahim , Miao Li Chee , Chien-Jen Chen , Fangfang Chen , Huashuai Chen , Shuohua Chen , Zhengming Chen , Ching-Yu Cheng , Bahman Cheraghian , Angela Chetrit , Ekaterina Chikova-Iscener , Arnaud Chiolero , Shu-Ti Chiou , María-Dolores Chirlaque , Belong Cho , Kaare Christensen , Diego G Christofaro , Jerzy Chudek , Renata Cifkova , Michelle Cilia , Eliza Cinteza , Frank Claessens , Janine Clarke , Els Clays , Emmanuel Cohen , Hans Concin , Susana C Confortin , Cyrus Cooper , Tara C Coppinger , Eva Corpeleijn , Simona Costanzo , Dominique Cottel , Chris Cowell , Cora L Craig , Amelia C Crampin , Ana B Crujeiras , Semánová Csilla , Alexandra M Cucu , Liufu Cui , Felipe V Cureau , Ewelina Czenczek-Lewandowska , Graziella D'Arrigo , Eleonora d'Orsi , Liliana Dacica , María Ángeles Dal Re Saavedra , Jean Dallongeville , Camilla T Damsgaard , Rachel Dankner , Thomas M Dantoft , Parasmani Dasgupta , Saeed Dastgiri , Luc Dauchet , Kairat Davletov , Guy De Backer , Dirk De Bacquer , Giovanni de Gaetano , Stefaan De Henauw , Paula Duarte de Oliveira , David De Ridder , Karin De Ridder , Susanne R de Rooij , Delphine De Smedt , Mohan Deepa , Alexander D Deev , Vincent Jr DeGennaro , Abbas Dehghan , Hélène Delisle , Francis Delpeuch , Stefaan Demarest , Elaine Dennison , Katarzyna Dereń , Valérie Deschamps , Meghnath Dhimal , Augusto F Di Castelnuovo , Juvenal Soares Dias-da-Costa , María Elena Díaz-Sánchez , Alejandro Diaz , Zivka Dika , Shirin Djalalinia , Visnja Djordjic , Ha Tp Do , Annette J Dobson , Maria Benedetta Donati , Chiara Donfrancesco , Silvana P Donoso , Angela Döring , Maria Dorobantu , Ahmad Reza Dorosty , Kouamelan Doua , Nico Dragano , Wojciech Drygas , Jia Li Duan , Charmaine A Duante , Priscilla Duboz , Rosemary B Duda , Vesselka Duleva , Virginija Dulskiene , Samuel C Dumith , Anar Dushpanova , Vilnis Dzerve , Elzbieta Dziankowska-Zaborszczyk , Ricky Eddie , Ebrahim Eftekhar , Eruke E Egbagbe , Robert Eggertsen , Sareh Eghtesad , Gabriele Eiben , Ulf Ekelund , Mohammad El-Khateeb , Jalila El Ati , Denise Eldemire-Shearer , Marie Eliasen , Paul Elliott , Reina Engle-Stone , Macia Enguerran , Rajiv T Erasmus , Raimund Erbel , Cihangir Erem , Louise Eriksen , Johan G Eriksson , Jorge Escobedo-de la Peña , Saeid Eslami , Ali Esmaeili , Alun Evans , David Faeh , Albina A Fakhretdinova , Caroline H Fall , Elnaz Faramarzi , Mojtaba Farjam , Victoria Farrugia Sant'Angelo , Farshad Farzadfar , Mohammad Reza Fattahi , Asher Fawwad , Francisco J Felix-Redondo , Trevor S Ferguson , Romulo A Fernandes , Daniel Fernández-Bergés , Daniel Ferrante , Thomas Ferrao , Marika Ferrari , Marco M Ferrario , Catterina Ferreccio , Eldridge Ferrer , Jean Ferrieres , Thamara Hubler Figueiró , Anna Fijalkowska , Günther Fink , Krista Fischer , Leng Huat Foo , Maria Forsner , Heba M Fouad , Damian K Francis , Maria do Carmo Franco , Ruth Frikke-Schmidt , Guillermo Frontera , Flavio D Fuchs , Sandra C Fuchs , Isti I Fujiati , Yuki Fujita , Matsuda Fumihiko , Takuro Furusawa , Zbigniew Gaciong , Mihai Gafencu , Andrzej Galbarczyk , Henrike Galenkamp , Daniela Galeone , Myriam Galfo , Fabio Galvano , Jingli Gao , Manoli Garcia-de-la-Hera , Marta García-Solano , Dickman Gareta , Sarah P Garnett , Jean-Michel Gaspoz , Magda Gasull , Adroaldo Cesar Araujo Gaya , Anelise Reis Gaya , Andrea Gazzinelli , Ulrike Gehring , Harald Geiger , Johanna M Geleijnse , Ali Ghanbari , Erfan Ghasemi , Oana-Florentina Gheorghe-Fronea , Simona Giampaoli , Francesco Gianfagna , Tiffany K Gill , Jonathan Giovannelli , Glen Gironella , Aleksander Giwercman , Konstantinos Gkiouras , Justyna Godos , Sibel Gogen , Marcel Goldberg , Rebecca A Goldsmith , David Goltzman , Santiago F Gómez , Aleksandra Gomula , Bruna Goncalves Cordeiro da Silva , Helen Gonçalves , David A Gonzalez-Chica , Marcela Gonzalez-Gross , Margot González-Leon , Juan P González-Rivas , Clicerio González-Villalpando , María-Elena González-Villalpando , Angel R Gonzalez , Frederic Gottrand , Antonio Pedro Graça , Sidsel Graff-Iversen , Dušan Grafnetter , Aneta Grajda , Maria G Grammatikopoulou , Ronald D Gregor , Tomasz Grodzicki , Else Karin Grøholt , Anders Grøntved , Giuseppe Grosso , Gabriella Gruden , Dongfeng Gu , Emanuela Gualdi-Russo , Pilar Guallar-Castillón , Andrea Gualtieri , Elias F Gudmundsson , Vilmundur Gudnason , Ramiro Guerrero , Idris Guessous , Andre L Guimaraes , Martin C Gulliford , Johanna Gunnlaugsdottir , Marc J Gunter , Xiu-Hua Guo , Yin Guo , Prakash C Gupta , Rajeev Gupta , Oye Gureje , Beata Gurzkowska , Enrique Gutiérrez-González , Laura Gutierrez , Felix Gutzwiller , Seongjun Ha , Farzad Hadaegh , Charalambos A Hadjigeorgiou , Rosa Haghshenas , Hamid Hakimi , Jytte Halkjær , Ian R Hambleton , Behrooz Hamzeh , Dominique Hange , Abu Am Hanif , Sari Hantunen , Jie Hao , Rachakulla Hari Kumar , Seyed Mohammad Hashemi-Shahri , Maria Hassapidou , Jun Hata , Teresa Haugsgjerd , Jiang He , Yuan He , Yuna He , Regina Heidinger-Felso , Mirjam Heinen , Tatjana Hejgaard , Marleen Elisabeth Hendriks , Rafael Dos Santos Henrique , Ana Henriques , Leticia Hernandez Cadena , Sauli Herrala , Victor M Herrera , Isabelle Herter-Aeberli , Ramin Heshmat , Allan G Hill , Sai Yin Ho , Suzanne C Ho , Michael Hobbs , Michelle Holdsworth , Reza Homayounfar , Clara Homs , Wilma M Hopman , Andrea Rvr Horimoto , Claudia M Hormiga , Bernardo L Horta , Leila Houti , Christina Howitt , Thein Thein Htay , Aung Soe Htet , Maung Maung Than Htike , Yonghua Hu , José María Huerta , Ilpo Tapani Huhtaniemi , Laetitia 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 Teresa A Olinto , Isabel O Oliveira , Mohd Azahadi Omar , Altan Onat , Sok King Ong , Lariane M Ono , Pedro Ordunez , Rui Ornelas , Ana P Ortiz , Pedro J Ortiz , Merete Osler , Clive Osmond , Sergej M Ostojic , Afshin Ostovar , Johanna A Otero , Kim Overvad , Ellis Owusu-Dabo , Fred Michel Paccaud , Cristina Padez , Ioannis Pagkalos , Elena Pahomova , Karina Mary de Paiva , Andrzej Pajak , Domenico Palli , Alberto Palloni , Luigi Palmieri , Wen-Harn Pan , Songhomitra Panda-Jonas , Arvind Pandey , Francesco Panza , Dimitrios Papandreou , Soon-Woo Park , Suyeon Park , Winsome R Parnell , Mahboubeh Parsaeian , Ionela M Pascanu , Patrick Pasquet , Nikhil D Patel , Ivan Pecin , Mangesh S Pednekar , Nasheeta Peer , Gao Pei , Sergio Viana Peixoto , Markku Peltonen , Alexandre C Pereira , Marco A Peres , Napoleón Pérez-Farinós , Cynthia M Pérez , Valentina Peterkova , Annette Peters , Astrid Petersmann , Janina Petkeviciene , Ausra Petrauskiene , Emanuela Pettenuzzo , Niloofar Peykari , Son Thai Pham , Rafael N Pichardo , Daniela Pierannunzio , Iris Pigeot , Hynek Pikhart , Aida Pilav , Lorenza Pilotto , Francesco Pistelli , Freda Pitakaka , Aleksandra Piwonska , Andreia N Pizarro , Pedro Plans-Rubió , Bee Koon Poh , Hermann Pohlabeln , Raluca M Pop , Stevo R Popovic , Miquel Porta , Georg Posch , Anil Poudyal , Dimitrios Poulimeneas , Hamed Pouraram , Farhad Pourfarzi , Akram Pourshams , Hossein Poustchi , Rajendra Pradeepa , Alison J Price , Jacqueline F Price , Rui Providencia , Jardena J Puder , Iveta Pudule , Soile E Puhakka , Maria Puiu , Margus Punab , Radwan F Qasrawi , Mostafa Qorbani , Tran Quoc Bao , Ivana Radic , Ricardas Radisauskas , Salar Rahimikazerooni , Mahfuzar Rahman , Mahmudur Rahman , Olli Raitakari , Manu Raj , Ellina Rakhimova , Sherali Rakhmatulloev , Ivo Rakovac , Sudha Ramachandra Rao , Ambady Ramachandran , Jacqueline Ramke , Elisabete Ramos , Rafel Ramos , Lekhraj Rampal , Sanjay Rampal , Vayia Rarra , Ramon A Rascon-Pacheco , Mette Rasmussen , Cassiano Ricardo Rech , Josep Redon , Paul Ferdinand M Reganit , Valéria Regecová , Luis Revilla , Abbas Rezaianzadeh , Lourdes Ribas-Barba , Robespierre Ribeiro , Elio Riboli , Adrian Richter , Fernando Rigo , Natascia Rinaldo , Tobias F Rinke de Wit , Ana Rito , Raphael M Ritti-Dias , Juan A Rivera , Cynthia Robitaille , Romana Roccaldo , Daniela Rodrigues , Fernando Rodríguez-Artalejo , María Del Cristo Rodriguez-Perez , Laura A Rodríguez-Villamizar , Ulla Roggenbuck , Rosalba Rojas-Martinez , Nipa Rojroongwasinkul , Dora Romaguera , Elisabetta L Romeo , Rafaela V Rosario , Annika Rosengren , Ian Rouse , Joel Gr Roy , Adolfo Rubinstein , Frank J Rühli , Jean-Bernard Ruidavets , Blanca Sandra Ruiz-Betancourt , Maria Ruiz-Castell , Emma Ruiz Moreno , Iuliia A Rusakova , Kenisha Russell Jonsson , Paola Russo , Petra Rust , Marcin Rutkowski , Charumathi Sabanayagam , Elena Sacchini , Harshpal S Sachdev , Alireza Sadjadi , Ali Reza Safarpour , Saeid Safiri , Nader Saki , Benoit Salanave , Eduardo Salazar Martinez , Diego Salmerón , Veikko Salomaa , Jukka T Salonen , Massimo Salvetti , Margarita Samoutian , Jose Sánchez-Abanto , Sandjaja , Susana Sans , Loreto Santa Marina , Diana A Santos , Ina S Santos , Lèlita C Santos , Maria Paula Santos , Osvaldo Santos , Rute Santos , Sara Santos Sanz , Jouko L Saramies , Luis B Sardinha , Nizal Sarrafzadegan , Thirunavukkarasu Sathish , Kai-Uwe Saum , Savvas Savva , Mathilde Savy , Norie Sawada , Mariana Sbaraini , Marcia Scazufca , Beatriz D Schaan , Angelika Schaffrath Rosario , Herman Schargrodsky , Anja Schienkiewitz , Sabine Schipf , Carsten O Schmidt , Ida Maria Schmidt , Peter Schnohr , Ben Schöttker , Sara Schramm , Stine Schramm , Helmut Schröder , Constance Schultsz , Aletta E Schutte , Aye Aye Sein , Rusidah Selamat , Vedrana Sember , Abhijit Sen , Idowu O Senbanjo , Sadaf G Sepanlou , Victor Sequera , Luis Serra-Majem , Jennifer Servais , Ludmila Ševcíková , Svetlana A Shalnova , Teresa Shamah-Levy , Morteza Shamshirgaran , Coimbatore Subramaniam Shanthirani , Maryam Sharafkhah , Sanjib K Sharma , Jonathan E Shaw , Amaneh Shayanrad , Ali Akbar Shayesteh , Lela Shengelia , Zumin Shi , Kenji Shibuya , Hana Shimizu-Furusawa , Dong Wook Shin , Majid Shirani , Rahman Shiri , Namuna Shrestha , Khairil Si-Ramlee , Alfonso Siani , Rosalynn Siantar , Abla M Sibai , Antonio M Silva , Diego Augusto Santos Silva , Mary Simon , Judith Simons , Leon A Simons , Agneta Sjöberg , Michael Sjöström , Gry Skodje , Jolanta Slowikowska-Hilczer , Przemyslaw Slusarczyk , Liam Smeeth , Hung-Kwan So , Fernanda Cunha Soares , Grzegorz Sobek , Eugène Sobngwi , Morten Sodemann , Stefan Söderberg , Moesijanti Ye Soekatri , Agustinus Soemantri , Reecha Sofat , Vincenzo Solfrizzi , Mohammad Hossein Somi , Emily Sonestedt , Yi Song , Thorkild Ia Sørensen , Elin P Sørgjerd , Charles Sossa Jérome , Victoria E Soto-Rojas , Aïcha Soumaré , Slavica Sovic , Bente Sparboe-Nilsen , Karen Sparrenberger , Angela Spinelli , Igor Spiroski , Jan A Staessen , Hanspeter Stamm , Maria G Stathopoulou , Kaspar Staub , Bill Stavreski , Jostein Steene-Johannessen , Peter Stehle , Aryeh D Stein , George S Stergiou , Jochanan Stessman , Ranko Stevanovic , Jutta Stieber , Doris Stöckl , Tanja Stocks , Jakub Stokwiszewski , Ekaterina Stoyanova , Gareth Stratton , Karien Stronks , Maria Wany Strufaldi , Lela Sturua , Ramón Suárez-Medina , Machi Suka , Chien-An Sun , Johan Sundström , Yn-Tz Sung , Jordi Sunyer , Paibul Suriyawongpaisal , Boyd A Swinburn , Rody G Sy , Holly E Syddall , René Charles Sylva , Moyses Szklo , Lucjan Szponar , E Shyong Tai , Mari-Liis Tammesoo , Abdonas Tamosiunas , Eng Joo Tan , Xun Tang , Maya Tanrygulyyeva , Frank Tanser , Yong Tao , Mohammed Rasoul Tarawneh , Jakob Tarp , Carolina B Tarqui-Mamani , Radka Taxová Braunerová , Anne Taylor , Julie Taylor , Félicité Tchibindat , William R Tebar , Grethe S Tell , Tania Tello , Yih Chung Tham , K R Thankappan , Holger Theobald , Xenophon Theodoridis , Lutgarde Thijs , Nihal Thomas , Betina H Thuesen , Lubica Tichá , Erik J Timmermans , Anne Tjonneland , Hanna K Tolonen , Janne S Tolstrup , Murat Topbas , Roman Topór-Madry , Liv Elin Torheim , María José Tormo , Michael J Tornaritis , Maties Torrent , Laura Torres-Collado , Stefania Toselli , Giota Touloumi , Pierre Traissac , Thi Tuyet-Hanh Tran , Dimitrios Trichopoulos , Antonia Trichopoulou , Oanh Th Trinh , Atul Trivedi , Lechaba Tshepo , Maria Tsigga , Shoichiro Tsugane , Azaliia M Tuliakova , Marshall K Tulloch-Reid , Fikru Tullu , Tomi-Pekka Tuomainen , Jaakko Tuomilehto , Maria L Turley , Gilad Twig , Per Tynelius , Themistoklis Tzotzas , Christophe Tzourio , Peter Ueda , Eunice Ugel , Flora Am Ukoli , Hanno Ulmer , Belgin Unal , Zhamyila Usupova , Hannu Mt Uusitalo , Nalan Uysal , Justina Vaitkeviciute , Gonzalo Valdivia , Susana Vale , Damaskini Valvi , Rob M van Dam , Johan Van der Heyden , Yvonne T van der Schouw , Koen Van Herck , Hoang Van Minh , Natasja M 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Weghuber , Wenbin Wei , Aneta Weres , Bo Werner , Peter H Whincup , Kurt Widhalm , Indah S Widyahening , Andrzej Wiecek , Rainford J Wilks , Johann Willeit , Peter Willeit , Julianne Williams , Tom Wilsgaard , Bogdan Wojtyniak , Roy A Wong-McClure , Andrew Wong , Jyh Eiin Wong , Tien Yin Wong , Jean Woo , Mark Woodward , Frederick C Wu , Jianfeng Wu , Li Juan Wu , Shouling Wu , Haiquan Xu , Liang Xu , Nor Azwany Yaacob , Uruwan Yamborisut , Weili Yan , Ling Yang , Xiaoguang Yang , Yang Yang , Nazan Yardim , Mehdi Yaseri , Tabara Yasuharu , Xingwang Ye , Panayiotis K Yiallouros , Moein Yoosefi , Akihiro Yoshihara , Qi Sheng You , San-Lin You , Novie O Younger-Coleman , Safiah Md Yusof , Ahmad Faudzi Yusoff , Luciana Zaccagni , Vassilis Zafiropulos , Ahmad A Zainuddin , Seyed Rasoul Zakavi , Farhad Zamani , Sabina Zambon , Antonis Zampelas , Hana Zamrazilová , Maria Elisa Zapata , Abdul Hamid Zargar , Ko Ko Zaw , Tomasz Zdrojewski , Kristyna Zejglicova , Tajana Zeljkovic Vrkic , Yi Zeng 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Lundqvist, Robert, Lunet, Nuno, Lunogelo, Charle, Lustigová, Michala, Łuszczki, Edyta, Ma, Guansheng, Ma, Jun, Ma, Xu, Machado-Coelho, George LL, Machado-Rodrigues, Aristides M, Macieira, Luisa M, Madar, Ahmed A, Maggi, Stefania, Magliano, Dianna J, Magnacca, Sara, Magriplis, Emmanuella, Mahasampath, Gowri, Maire, Bernard, Majer, Marjeta, Makdisse, Marcia, Mäki, Päivi, Malekzadeh, Fatemeh, Malekzadeh, Reza, Malhotra, Rahul, Rao, Kodavanti Mallikharjuna, Malyutina, Sofia K, Maniego, Lynell V, Manios, Yanni, Mann, Jim I, Mansour-Ghanaei, Fariborz, Manzato, Enzo, Margozzini, Paula, Markaki, Anastasia, Markey, Oonagh, Ioannidou, Eliza Markidou, Marques-Vidal, Pedro, Marques, Larissa Pruner, Marrugat, Jaume, Martin-Prevel, Yve, Martin, Rosemarie, Martorell, Reynaldo, Martos, Eva, Maruszczak, Katharina, Marventano, Stefano, Mascarenhas, Luis P, Masoodi, Shariq R, Mathiesen, Ellisiv B, Mathur, Prashant, Matijasevich, Alicia, Matsha, Tandi E, Mavrogianni, Christina, Mazur, Artur, Mbanya, Jean Claude N, McFarlane, Shelly R, McGarvey, Stephen T, McKee, Martin, McLachlan, Stela, McLean, Rachael M, McLean, Scott B, McNulty, Breige A, Benchekor, Sounnia Mediene, Medzioniene, Jurate, Mehdipour, Parinaz, Mehlig, Kirsten, Mehrparvar, Amir Houshang, Meirhaeghe, Aline, Meisfjord, Jørgen, Meisinger, Christa, Menezes, Ana Maria B, Menon, Geetha R, Mensink, Gert BM, Menzano, Maria Teresa, Mereke, Alibek, Meshram, Indrapal I, Metspalu, Andre, Meyer, Haakon E, Mi, Jie, Michaelsen, Kim F, Michels, Nathalie, Mikkel, Kairit, Milkowska, Karolina, Miller, Jody C, Minderico, Cláudia S, Mini, GK, Miquel, Juan Francisco, Mirjalili, Mohammad Reza, Mirkopoulou, Daphne, Mirrakhimov, Erkin, Mišigoj-Durakovic, Marjeta, Mistretta, Antonio, Mocanu, Veronica, Modesti, Pietro A, Moghaddam, Sahar Saeedi, Mohajer, Bahram, Mohamed, Mostafa K, Mohamed, Shukri F, Mohammad, Kazem, Mohammadi, Zahra, Mohammadifard, Noushin, Mohammadpourhodki, Reza, Mohan, Viswanathan, Mohanna, Salim, Yusoff, Muhammad Fadhli Mohd, Mohebbi, Iraj, Mohebi, Farnam, Moitry, Marie, Molbo, Drude, Møllehave, Line T, Møller, Niels C, Molnár, Déne, Momenan, Amirabba, Mondo, Charles K, Monroy-Valle, Michele, Monterrubio-Flores, Eric, Monyeki, Kotsedi Daniel K, Moon, Jin Soo, Moosazadeh, Mahmood, Moreira, Leila B, Morejon, Alain, Moreno, Luis A, Morgan, Karen, Morin, Suzanne N, Mortensen, Erik Lykke, Moschonis, George, Mossakowska, Malgorzata, Mostafa, Aya, Mota-Pinto, Anabela, Mota, Jorge, Motlagh, Mohammad Esmaeel, Motta, Jorge, Moura-dos-Santos, Marcos André, Mridha, Malay K, Msyamboza, Kelias P, Mu, Thet Thet, Muc, Magdalena, Mugoša, Boban, Muiesan, Maria L, Mukhtorova, Parvina, Müller-Nurasyid, Martina, Murphy, Neil, Mursu, Jaakko, Murtagh, Elaine M, Musa, Kamarul Imran, Milanovic, Sanja Music, Musil, Vera, Mustafa, Norlaila, Nabipour, Iraj, Naderimagham, Shohreh, Nagel, Gabriele, Naidu, Balkish M, Najafi, Farid, Nakamura, Harunobu, Námešná, Jana, Ei K Nang, Ei, Nangia, Vinay B, Nankap, Martin, Narake, Sameer, Nardone, Paola, Nauck, Matthia, Neal, William A, Nejatizadeh, Azim, Nekkantti, Chandini, Nelis, Keiu, Nelis, Lii, Nenko, Ilona, Neovius, Martin, Nervi, Flavio, Nguyen, Chung T, Nguyen, Nguyen D, Nguyen, Quang Ngoc, Nieto-Martínez, Ramfis E, Nikitin, Yury P, Ning, Guang, Ninomiya, Toshiharu, Nishtar, Sania, Noale, Marianna, Noboa, Oscar A, Nogueira, Helena, Norat, Teresa, Nordendahl, Maria, Nordestgaard, Børge G, Noto, Davide, Nowak-Szczepanska, Natalia, Al Nsour, Mohannad, Nuhoglu, Irfan, Nurk, Eha, O'Neill, Terence W, O'Reilly, Dermot, Obreja, Galina, Ochimana, Caleb, Ochoa-Avilés, Angélica M, Oda, Eiji, Oh, Kyungwon, Ohara, Kumiko, Ohlsson, Clae, Ohtsuka, Ryutaro, Olafsson, Örn, Olinto, Maria Teresa A, Oliveira, Isabel O, Omar, Mohd Azahadi, Onat, Altan, Ong, Sok King, Ono, Lariane M, Ordunez, Pedro, Ornelas, Rui, Ortiz, Ana P, Ortiz, Pedro J, Osler, Merete, Osmond, Clive, Ostojic, Sergej M, Ostovar, Afshin, Otero, Johanna A, Overvad, Kim, Owusu-Dabo, Elli, Paccaud, Fred Michel, Padez, Cristina, Pagkalos, Ioanni, Pahomova, Elena, de Paiva, Karina Mary, Pajak, Andrzej, Palli, Domenico, Palloni, Alberto, Palmieri, Luigi, Pan, Wen-Harn, Panda-Jonas, Songhomitra, Pandey, Arvind, Panza, Francesco, Papandreou, Dimitrio, Park, Soon-Woo, Park, Suyeon, Parnell, Winsome R, Parsaeian, Mahboubeh, Pascanu, Ionela M, Pasquet, Patrick, Patel, Nikhil D, Pecin, Ivan, Pednekar, Mangesh S, Peer, Nasheeta, Pei, Gao, Peixoto, Sergio Viana, Peltonen, Markku, Pereira, Alexandre C, Peres, Marco A, Pérez-Farinós, Napoleón, Pérez, Cynthia M, Peterkova, Valentina, Peters, Annette, Petersmann, Astrid, Petkeviciene, Janina, Petrauskiene, Ausra, Pettenuzzo, Emanuela, Peykari, Niloofar, Pham, Son Thai, Pichardo, Rafael N, Pierannunzio, Daniela, Pigeot, Iri, Pikhart, Hynek, Pilav, Aida, Pilotto, Lorenza, Pistelli, Francesco, Pitakaka, Freda, Piwonska, Aleksandra, Pizarro, Andreia N, Plans-Rubió, Pedro, Poh, Bee Koon, Pohlabeln, Hermann, Pop, Raluca M, Popovic, Stevo R, Porta, Miquel, Posch, Georg, Poudyal, Anil, Poulimeneas, Dimitrio, Pouraram, Hamed, Pourfarzi, Farhad, Pourshams, Akram, Poustchi, Hossein, Pradeepa, Rajendra, Price, Alison J, Price, Jacqueline F, Providencia, Rui, Puder, Jardena J, Pudule, Iveta, Puhakka, Soile E, Puiu, Maria, Punab, Margu, Qasrawi, Radwan F, Qorbani, Mostafa, Bao, Tran Quoc, Radic, Ivana, Radisauskas, Ricarda, Rahimikazerooni, Salar, Rahman, Mahfuzar, Rahman, Mahmudur, Raitakari, Olli, Raj, Manu, Rakhimova, Ellina, Rakhmatulloev, Sherali, Rakovac, Ivo, Rao, Sudha Ramachandra, Ramachandran, Ambady, Ramke, Jacqueline, Ramos, Elisabete, Ramos, Rafel, Rampal, Lekhraj, Rampal, Sanjay, Rarra, Vayia, Rascon-Pacheco, Ramon A, Rasmussen, Mette, Rech, Cassiano Ricardo, Redon, Josep, Reganit, Paul Ferdinand M, Regecová, Valéria, Revilla, Lui, Rezaianzadeh, Abba, Ribas-Barba, Lourde, Ribeiro, Robespierre, Riboli, Elio, Richter, Adrian, Rigo, Fernando, Rinaldo, Natascia, de Wit, Tobias F Rinke, Rito, Ana, Ritti-Dias, Raphael M, Rivera, Juan A, Robitaille, Cynthia, Roccaldo, Romana, Rodrigues, Daniela, Rodríguez-Artalejo, Fernando, del Cristo Rodriguez-Perez, María, Rodríguez-Villamizar, Laura A, Roggenbuck, Ulla, Rojas-Martinez, Rosalba, Rojroongwasinkul, Nipa, Romaguera, Dora, Romeo, Elisabetta L, Rosario, Rafaela V, Rosengren, Annika, Rouse, Ian, Roy, Joel GR, Rubinstein, Adolfo, Rühli, Frank J, Ruidavets, Jean-Bernard, Ruiz-Betancourt, Blanca Sandra, Ruiz-Castell, Maria, Moreno, Emma Ruiz, Rusakova, Iuliia A, Jonsson, Kenisha Russell, Russo, Paola, Rust, Petra, Rutkowski, Marcin, Sabanayagam, Charumathi, Sacchini, Elena, Sachdev, Harshpal S, Sadjadi, Alireza, Safarpour, Ali Reza, Safiri, Saeid, Saki, Nader, Salanave, Benoit, Martinez, Eduardo Salazar, Salmerón, Diego, Salomaa, Veikko, Salonen, Jukka T, Salvetti, Massimo, Samoutian, Margarita, Sánchez-Abanto, Jose, Sandjaja, null, Sans, Susana, Marina, Loreto Santa, Santos, Diana A, Santos, Ina S, Santos, Lèlita C, Santos, Maria Paula, Santos, Osvaldo, Santos, Rute, Sanz, Sara Santo, Saramies, Jouko L, Sardinha, Luis B, Sarrafzadegan, Nizal, Sathish, Thirunavukkarasu, Saum, Kai-Uwe, Savva, Savva, Savy, Mathilde, Sawada, Norie, Sbaraini, Mariana, Scazufca, Marcia, Schaan, Beatriz D, Rosario, Angelika Schaffrath, Schargrodsky, Herman, Schienkiewitz, Anja, Schipf, Sabine, Schmidt, Carsten O, Schmidt, Ida Maria, Schnohr, Peter, Schöttker, Ben, Schramm, Sara, Schramm, Stine, Schröder, Helmut, Schultsz, Constance, Schutte, Aletta E, Sein, Aye Aye, Selamat, Rusidah, Sember, Vedrana, Sen, Abhijit, Senbanjo, Idowu O, Sepanlou, Sadaf G, Sequera, Victor, Serra-Majem, Lui, Servais, Jennifer, Ševcíková, Ludmila, Shalnova, Svetlana A, Shamah-Levy, Teresa, Shamshirgaran, Morteza, Shanthirani, Coimbatore Subramaniam, Sharafkhah, Maryam, Sharma, Sanjib K, Shaw, Jonathan E, Shayanrad, Amaneh, Shayesteh, Ali Akbar, Shengelia, Lela, Shi, Zumin, Shibuya, Kenji, Shimizu-Furusawa, Hana, Shin, Dong Wook, Shirani, Majid, Shiri, Rahman, Shrestha, Namuna, Si-Ramlee, Khairil, Siani, Alfonso, Siantar, Rosalynn, Sibai, Abla M, Silva, Antonio M, Silva, Diego Augusto Santo, Simon, Mary, Simons, Judith, Simons, Leon A, Sjöberg, Agneta, Sjöström, Michael, Skodje, Gry, Slowikowska-Hilczer, Jolanta, Slusarczyk, Przemyslaw, Smeeth, Liam, So, Hung-Kwan, Soares, Fernanda Cunha, Sobek, Grzegorz, Sobngwi, Eugène, Sodemann, Morten, Söderberg, Stefan, Soekatri, Moesijanti YE, Soemantri, Agustinu, Sofat, Reecha, Solfrizzi, Vincenzo, Somi, Mohammad Hossein, Sonestedt, Emily, Song, Yi, Sørensen, Thorkild IA, Sørgjerd, Elin P, Jérome, Charles Sossa, Soto-Rojas, Victoria E, Soumaré, Aïcha, Sovic, Slavica, Sparboe-Nilsen, Bente, Sparrenberger, Karen, Spinelli, Angela, Spiroski, Igor, Staessen, Jan A, Stamm, Hanspeter, Stathopoulou, Maria G, Staub, Kaspar, Stavreski, Bill, Steene-Johannessen, Jostein, Stehle, Peter, Stein, Aryeh D, Stergiou, George S, Stessman, Jochanan, Stevanovic, Ranko, Stieber, Jutta, Stöckl, Dori, Stocks, Tanja, Stokwiszewski, Jakub, Stoyanova, Ekaterina, Stratton, Gareth, Stronks, Karien, Strufaldi, Maria Wany, Sturua, Lela, Suárez-Medina, Ramón, Suka, Machi, Sun, Chien-An, Sundström, Johan, Sung, Yn-Tz, Sunyer, Jordi, Suriyawongpaisal, Paibul, Swinburn, Boyd A, Sy, Rody G, Syddall, Holly E, Sylva, René Charle, Szklo, Moyse, Szponar, Lucjan, Tai, E Shyong, Tammesoo, Mari-Lii, Tamosiunas, Abdona, Tan, Eng Joo, Tang, Xun, Tanrygulyyeva, Maya, Tanser, Frank, Tao, Yong, Tarawneh, Mohammed Rasoul, Tarp, Jakob, Tarqui-Mamani, Carolina B, Braunerová, Radka Taxová, Taylor, Anne, Taylor, Julie, Tchibindat, Félicité, Tebar, William R, Tell, Grethe S, Tello, Tania, Tham, Yih Chung, Thankappan, KR, Theobald, Holger, Theodoridis, Xenophon, Thijs, Lutgarde, Thomas, Nihal, Thuesen, Betina H, Tichá, Lubica, Timmermans, Erik J, Tjonneland, Anne, Tolonen, Hanna K, Tolstrup, Janne S, Topbas, Murat, Topór-Madry, Roman, Torheim, Liv Elin, Tormo, María José, Tornaritis, Michael J, Torrent, Matie, Torres-Collado, Laura, Toselli, Stefania, Touloumi, Giota, Traissac, Pierre, Tran, Thi Tuyet-Hanh, Trichopoulos, Dimitrio, Trichopoulou, Antonia, Trinh, Oanh TH, Trivedi, Atul, Tshepo, Lechaba, Tsigga, Maria, Tsugane, Shoichiro, Tuliakova, Azaliia M, Tulloch-Reid, Marshall K, Tullu, Fikru, Tuomainen, Tomi-Pekka, Tuomilehto, Jaakko, Turley, Maria L, Twig, Gilad, Tynelius, Per, Tzotzas, Themistokli, Tzourio, Christophe, Ueda, Peter, Ugel, Eunice, Ukoli, Flora AM, Ulmer, Hanno, Unal, Belgin, Usupova, Zhamyila, Uusitalo, Hannu MT, Uysal, Nalan, Vaitkeviciute, Justina, Valdivia, Gonzalo, Vale, Susana, Valvi, Damaskini, van Dam, Rob M, Van der Heyden, Johan, van der Schouw, Yvonne T, Van Herck, Koen, Van Minh, Hoang, Van Schoor, Natasja M, van Valkengoed, Irene GM, Vanderschueren, Dirk, Vanuzzo, Diego, Varbo, Anette, Varela-Moreiras, Gregorio, Varona-Pérez, Patricia, Vasan, Senthil K, Vega, Toma, Veidebaum, Tooma, Velasquez-Melendez, Gustavo, Velika, Biruta, Veronesi, Giovanni, Verschuren, WM Monique, Victora, Cesar G, Viegi, Giovanni, Viet, Lucie, Villalpando, Salvador, Vineis, Paolo, Vioque, Jesu, Virtanen, Jyrki K, Visser, Marjolein, Visvikis-Siest, Sophie, Viswanathan, Bharathi, Vladulescu, Mihaela, Vlasoff, Tiina, Vocanec, Dorja, Vollenweider, Peter, Völzke, Henry, Voutilainen, Ari, Voutilainen, Sari, Vrijheid, Martine, Vrijkotte, Tanja GM, Wade, Alisha N, Wagner, Aline, Waldhör, Thoma, Walton, Janette, Wambiya, Elvis OA, Bebakar, Wan Mohamad Wan, Mohamud, Wan Nazaimoon Wan, de Souza Wanderley Júnior, Rildo, Wang, Ming-Dong, Wang, Ningli, Wang, Qian, Wang, Xiangjun, Wang, Ya Xing, Wang, Ying-Wei, Wannamethee, S Goya, Wareham, Nichola, Weber, Adelheid, Wedderkopp, Niel, Weerasekera, Deepa, Weghuber, Daniel, Wei, Wenbin, Weres, Aneta, Werner, Bo, Whincup, Peter H, Widhalm, Kurt, Widyahening, Indah S, Wiecek, Andrzej, Wilks, Rainford J, Willeit, Johann, Willeit, Peter, Williams, Julianne, Wilsgaard, Tom, Wojtyniak, Bogdan, Wong-McClure, Roy A, Wong, Andrew, Wong, Jyh Eiin, Wong, Tien Yin, Woo, Jean, Woodward, Mark, Wu, Frederick C, Wu, Jianfeng, Wu, Li Juan, Wu, Shouling, Xu, Haiquan, Xu, Liang, Yaacob, Nor Azwany, Yamborisut, Uruwan, Yan, Weili, Yang, Ling, Yang, Xiaoguang, Yang, Yang, Yardim, Nazan, Yaseri, Mehdi, Yasuharu, Tabara, Ye, Xingwang, Yiallouros, Panayiotis K, Yoosefi, Moein, Yoshihara, Akihiro, You, Qi Sheng, You, San-Lin, Younger-Coleman, Novie O, Md Yusof, Safiah, Yusoff, Ahmad Faudzi, Zaccagni, Luciana, Zafiropulos, Vassili, Zainuddin, Ahmad A, Zakavi, Seyed Rasoul, Zamani, Farhad, Zambon, Sabina, Zampelas, Antoni, Zamrazilová, Hana, Zapata, Maria Elisa, Zargar, Abdul Hamid, Ko Zaw, Ko, Zdrojewski, Tomasz, Zejglicova, Kristyna, Vrkic, Tajana Zeljkovic, Zeng, Yi, Zhang, Luxia, Zhang, Zhen-Yu, Zhao, Dong, Zhao, Ming-Hui, Zhao, Wenhua, Zhen, Shiqi, Zheng, Wei, Zheng, Yingfeng, Zholdin, Bekbolat, Zhou, Maigeng, Zhu, Dan, Zins, Marie, Zitt, Emanuel, Zocalo, Yanina, Cisneros, Julio Zuñiga, Zuziak, Monika, Ezzati, Majid, Filippi, Sarah, Cohortes épidémiologiques en population (CONSTANCES), Université de 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

16. Multiethnic Genome-Wide Association Study of Subclinical Atherosclerosis in Individuals With Type 2 Diabetes

Author: Stefan Weiss, Gauti Kjartan Gislason, Matthew J. Budoff, Valborg Gudmundsdottir, Xiuqing Guo, Lawrence F. Bielak, Joshua C. Bis, Jie Yao, Latchezar Dimitrov, Leslie A. Lange, Patricia A. Peyser, Lingyi Lu, Vilmundur Gudnason, Jerome I. Rotter, Barry I. Freedman, Lihua Wang, M. Arfan Ikram, Mohsen Ghanbari, Yingchang Lu, Jiaxi Zhu, Elias F Gudmundsson, Gerardo Heiss, Yi-Ping Fu, Maryam Kavousi, Shih-Jen Hwang, Sharon L.R. Kardia, Laura M. Raffield, André G. Uitterlinden, Carl D. Langefeld, Donald W. Bowden, Ping An, Daniel Bos, Kent D. Taylor, Ulf Schminke, Albert V. Smith, Bruce M. Psaty, James G. Wilson, Shyh-Huei Chen, Maggie C.Y. Ng, Christopher J. O'Donnell, Mary F. Feitosa, Nora Franceschini, Epidemiology, Radiology & Nuclear Medicine, and Internal Medicine
Subjects: 0301 basic medicine, Aging, Carotid arteries, Genome-wide association study, Type 2 diabetes, 030204 cardiovascular system & hematology, Cardiovascular, Coronary artery disease, 0302 clinical medicine, 2.1 Biological and endogenous factors, Aetiology, Diabetes, General Medicine, Heart Disease, cardiovascular system, Cardiology, medicine.symptom, Type 2, coronary artery disease, medicine.medical_specialty, carotid intima-media thickness, Black People, Asymptomatic, White People, Article, Diabetes Complications, 03 medical and health sciences, SDG 3 - Good Health and Well-being, Internal medicine, Diabetes Mellitus, Genetics, medicine, Humans, Genetic Predisposition to Disease, cardiovascular diseases, Heart Disease - Coronary Heart Disease, genome-wide association study, business.industry, Prevention, Human Genome, nutritional and metabolic diseases, Atherosclerosis, medicine.disease, Good Health and Well Being, 030104 developmental biology, Diabetes Mellitus, Type 2, Genetic Loci, Subclinical atherosclerosis, Coronary artery calcification, business, Genome-Wide Association Study
Abstract: Background: Coronary artery calcification (CAC) and carotid artery intima-media thickness (cIMT) are measures of subclinical atherosclerosis in asymptomatic individuals and strong risk factors for cardiovascular disease. Type 2 diabetes (T2D) is an independent cardiovascular disease risk factor that accelerates atherosclerosis. Methods: We performed meta-analyses of genome-wide association studies in up to 2500 T2D individuals of European ancestry (EA) and 1590 T2D individuals of African ancestry with or without exclusion of prevalent cardiovascular disease, for CAC measured by cardiac computed tomography, and 3608 individuals of EA and 838 individuals of African ancestry with T2D for cIMT measured by ultrasonography within the CHARGE (Cohorts for Heart and Aging Research in Genomic Epidemiology) Consortium. Results: We replicated 2 loci (rs9369640 and rs9349379 near PHACTR1 and rs10757278 near CDKN2B ) for CAC and one locus for cIMT (rs7412 and rs445925 near APOE-APOC1 ) that were previously reported in the general EA populations. We identified one novel CAC locus (rs8000449 near CSNK1A1L/LINC00547/POSTN at 13q13.3) at P =2.0×10 -8 in EA. No additional loci were identified with the meta-analyses of EA and African ancestry. The expression quantitative trait loci analysis with nearby expressed genes derived from arterial wall and metabolic tissues from the Genotype-Tissue Expression project pinpoints POSTN , encoding a matricellular protein involved in bone formation and bone matrix organization, as the potential candidate gene at this locus. In addition, we found significant associations ( P -4 ) for 3 previously reported coronary artery disease loci for these subclinical atherosclerotic phenotypes (rs2891168 near CDKN2B-AS1 and rs11170820 near FLJ12825 for CAC, and rs7412 near APOE for cIMT). Conclusions: Our results provide potential biological mechanisms that could link CAC and cIMT to increased cardiovascular disease risk in individuals with T2D.
Published: 2021

17. A Proteogenomic Signature of Age-related Macular Degeneration in Blood

Author: Valur Emilsson, Fridbert Jonasson, Brynjolfur G. Jonsson, Xin Liu, Valborg Gudmundsdottir, Tony Walshe, Chia-Ling Huang, Thorarinn Jonmundsson, Sandra Jose, Qin Zhang, Barrett Leehy, Yiyun Zhang, Lenore J. Launer, Vilmundur Gudnason, Thor Aspelund, Elias F. Gudmundsson, John Lamb, Michael Twarog, Qian Huang, Nancy Finkel, Lori L. Jennings, Rebecca Pitts, Mary Frances Cotch, Cynthia L. Grosskreutz, Joseph Loureiro, Stephen Poor, Andrew Anh Nguyen, Robert Esterberg, and Sha-Mei Liao
Subjects: education.field_of_study, genetic structures, Population, Genome-wide association study, Disease, Biology, Macular degeneration, medicine.disease, Bioinformatics, eye diseases, Factor H, Mendelian randomization, medicine, sense organs, education, CFHR5, Genetic association
Abstract: Age-related macular degeneration (AMD) is one of the most frequent causes of visual impairment in the elderly population. The overall etiology of AMD is complex and still poorly understood, though age, obesity, smoking, and high-density lipoprotein are known risk factors. In one of the first successful reported genome-wide association studies (GWAS), common genetic variants were strongly associated with AMD, including variants within the complement factor H (CFH) gene. To date, 34 genomic regions have been linked to AMD; however, the genes that mediate the risk remain largely unknown, indicating that novel approaches to identifying causal candidates are needed. Recent advances in proteomic technology have exposed the serum proteome’s depth and complexity. In the Age, Gene/Environment Susceptibility Reykjavik Study (AGES-RS), a broad population-based study of the elderly (N = 5764), levels of 4137 human serum proteins and associated networks were integrated with established genetic risk loci for AMD, revealing many predicted as well as novel proteins and pathways, linked to the disease. Serum proteins were also found to reflect AMD severity independent of genetics and predict progression from early to advanced AMD after five years in this population. A two-sample Mendelian randomization study of five proteins associated with AMD found CFHR1, CFHR5, and FUT5 to be causally related to the disease, all of which were directionally consistent with the observational estimates. This study provides a robust and unique framework for elucidating the pathobiology of AMD.
Published: 2021

18. A genome-wide association study of serum proteins reveals shared loci with common diseases

Author: Alexander Gudjonsson, L. J. Launer, Lamb, Gudnason, Brynjolfur G. Jonsson, Gudmundsdottir, Thor Aspelund, Emilsson, Elias F Gudmundsson, Gisli Thor Axelsson, and Lori L. Jennings
Subjects: Genetics, Genome-wide association study, Disease, Biology, Allele, Protein network, Blood proteins, Phenotype, Loss function, Genetic association
Abstract: With the growing number of genetic association studies, the genotype-phenotype atlas has become increasingly more complex, yet the functional consequences of most disease associated alleles is not understood. The measurement of protein level variation in solid tissues and biofluids integrated with genetic variants offers a path to deeper functional insights. Here we present a large-scale proteogenomic study in 5,368 individuals, revealing 4,113 independent associations between genetic variants and 2,099 serum proteins, of which 37% are previously unreported. The majority of bothcis- andtrans-acting genetic signals are unique for a single protein, although our results also highlight numerous highly pleiotropic genetic effects on protein levels and demonstrate that a protein’s genetic association profile reflects certain characteristics of the protein, including its location in protein networks, tissue specificity and intolerance to loss of function mutations. Integrating protein measurements with deep phenotyping of the cohort, we observe substantial enrichment of phenotype associations for serum proteins regulated by established GWAS loci, and offer new insights into the interplay between genetics, serum protein levels and complex disease.
Published: 2021

19. Imaging Patterns Are Associated with Interstitial Lung Abnormality Progression and Mortality

Author: Hiroto Hatabu, Gary M. Hunninghake, Gisli Thor Axelsson, Tomoyuki Hida, Elias F. Gudmundsson, Vilmundur Gudnason, Gudny Eiriksdottir, Michael H. Cho, Tetsuro Araki, David A. Schwartz, Noriyuki Tomiyama, Masahiro Yanagawa, Hiroshi Honda, Mizuki Nishino, Osamu Honda, Ivan O. Rosas, Rachel K. Putman, Ezra R. Miller, George R. Washko, and Gunnar Gudmundsson
Subjects: Pulmonary and Respiratory Medicine, Pathology, medicine.medical_specialty, Lung, medicine.diagnostic_test, business.industry, Computed tomography, Critical Care and Intensive Care Medicine, medicine.disease, 03 medical and health sciences, Idiopathic pulmonary fibrosis, 0302 clinical medicine, medicine.anatomical_structure, 030228 respiratory system, Pulmonary fibrosis, medicine, 030212 general & internal medicine, Mild form, Abnormality, business
Abstract: Rationale: Interstitial lung abnormalities (ILA) are radiologic abnormalities on chest computed tomography scans that have been associated with an early or mild form of pulmonary fibrosis. Although...
Published: 2019

20. Large-scale plasma proteomic analysis identifies proteins and pathways associated with dementia risk

Author: Valur Emilsson, Ron C. Hoogeveen, Jingning Zhang, Aozhou Wu, Morgan E. Grams, Christie M. Ballantyne, Lori L. Jennings, Yunju Yang, Nilanjan Chatterjee, Peter Ganz, Rebecca F. Gottesman, Jingsha Chen, Vilmundur Gudnason, Myriam Fornage, Eric Boerwinkle, Adrienne Tin, Thomas H. Mosley, Lenore J. Launer, Josef Coresh, Keenan A. Walker, Elias F. Gudmundsson, Linda Zhou, Kevin J. Sullivan, Scott L. Zeger, and Natalie Daya
Subjects: Aging, Neuroscience (miscellaneous), Disease, Neurodegenerative, Alzheimer's Disease, Bioinformatics, Article, Pathogenesis, Atrophy, Immune system, Clinical Research, mental disorders, Mendelian randomization, Acquired Cognitive Impairment, medicine, 2.1 Biological and endogenous factors, Dementia, Aetiology, business.industry, Prevention, Neurosciences, Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD), medicine.disease, Blood proteins, Brain Disorders, Neurological, Cohort, Geriatrics and Gerontology, business, Biotechnology
Abstract: The plasma proteomic changes that precede the onset of dementia could yield insights into disease biology and highlight new biomarkers and avenues for intervention. We quantified 4,877 plasma proteins in nondemented older adults in the Atherosclerosis Risk in Communities cohort and performed a proteome-wide association study of dementia risk over five years (n = 4,110; 428 incident cases). Thirty-eight proteins were associated with incident dementia after Bonferroni correction. Of these, 16 were also associated with late-life dementia risk when measured in plasma collected nearly 20 years earlier, during mid-life. Two-sample Mendelian randomization causally implicated two dementia-associated proteins (SVEP1 and angiostatin) in Alzheimer’s disease. SVEP1, an immunologically relevant cellular adhesion protein, was found to be part of larger dementia-associated protein networks, and circulating levels were associated with atrophy in brain regions vulnerable to Alzheimer’s pathology. Pathway analyses for the broader set of dementia-associated proteins implicated immune, lipid, metabolic signaling and hemostasis pathways in dementia pathogenesis. Walker et al. report a proteome-wide association study that identifies 38 candidate proteins in nondemented older adults that are associated with future dementia risk. Pathway analysis of these proteins implicates immune, lipid, metabolic signaling and hemostasis pathways in dementia pathogenesis.
Published: 2021

21. Progression of traction bronchiectasis/bronchiolectasis in interstitial lung abnormalities is associated with increased all-cause mortality: Age Gene/Environment Susceptibility-Reykjavik Study

Author: Gunnar Gudmundsson, David C. Christiani, Hiroshi Honda, Mizuki Nishino, David A. Lynch, Akinori Hata, Tetsuro Araki, Takuya Hino, Osamu Honda, Vilmundur Gudnason, Noriyuki Tomiyama, Rachel K. Putman, Gary M. Hunninghake, Hiroto Hatabu, Raul San Jose Estepar, Kousei Ishigami, Masahiro Jinzaki, George R. Washko, Masahiro Yanagawa, Takeshi Kamitani, Takeshi Johkoh, Elias F. Gudmundsson, Yoshitake Yamada, Tomoyuki Hida, Vladimir I. Valtchinov, and Junwei Lu
Subjects: medicine.medical_specialty, BMI, body mass index, R895-920, Gastroenterology, Article, Pulmonary fibrosis, 030218 nuclear medicine & medical imaging, OS, overall survival, TB, traction bronchiectasis, TBI-R2, traction bronchiectasis/bronchiolecetasis index on Round 2, Medical physics. Medical radiology. Nuclear medicine, 03 medical and health sciences, 0302 clinical medicine, Usual interstitial pneumonia, Internal medicine, medicine, AGES-Reykjavik Study, Age Gene/Environment Susceptibility-Reykjavik Study, Radiology, Nuclear Medicine and imaging, Honeycombing, Interstitial lung abnormality, Traction bronchiectasis, Age Gene/Environment Susceptibility-Reykjavik Study, Lung, Bronchiectasis, Proportional hazards model, business.industry, Hazard ratio, Interstitial lung disease, medicine.disease, HR, hazard ratio, medicine.anatomical_structure, 030220 oncology & carcinogenesis, TBI, traction bronchiectasis/bronchiolecetasis index, ILD, interstitial lung disease, ILA, interstitial lung abnormalities, business
Abstract: Highlights • TB progressed in 58.4 % (191/327). More than 90 % of participants with TBI = 2 or 3 (51/56) had TB progression. • TB progression was associated with increased mortality (adjusted HR = 1.68, P, Purpose The aim of this study is to assess the role of traction bronchiectasis/bronchiolectasis and its progression as a predictor for early fibrosis in interstitial lung abnormalities (ILA). Methods Three hundred twenty-seven ILA participants out of 5764 in the Age, Gene/Environment Susceptibility (AGES)-Reykjavik Study who had undergone chest CT twice with an interval of approximately five-years were enrolled in this study. Traction bronchiectasis/bronchiolectasis index (TBI) was classified on a four-point scale: 0, ILA without traction bronchiectasis/bronchiolectasis; 1, ILA with bronchiolectasis but without bronchiectasis or architectural distortion; 2, ILA with mild to moderate traction bronchiectasis; 3, ILA and severe traction bronchiectasis and/or honeycombing. Traction bronchiectasis (TB) progression was classified on a five-point scale: 1, Improved; 2, Probably improved; 3, No change; 4, Probably progressed; 5, Progressed. Overall survival (OS) among participants with different TB Progression Score and between the TB progression group and No TB progression group was also investigated. Hazard radio (HR) was estimated with Cox proportional hazards model. Results The higher the TBI at baseline, the higher TB Progression Score (P
Published: 2021

22. 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. McGarvey, Patrick Pasquet, Farnam Mohebi, Nader Saki, Aida Pilav, Azim Nejatizadeh, Marianna Noale, Habiba Ben Romdhane, Luís B. Sardinha, Laura Lauria, Jun Hata, Kodanda R Kanala, Gert B. M. Mensink, Nils Lehmann, Elio Riboli, Carolina Tarqui-Mamani, Rodrigo M. Carrillo-Larco, Rosangela Fernandes Lucena Batista, Victoria E Soto-Rojas, Luis Serra-Majem, Martina Müller-Nurasyid, Felipe Vogt Cureau, Lekhraj Rampal, Zhamilya Battakova, Ludmila Sevcikova, Suhaila Abdul Ghaffar, Fikru Tullu, Aung Soe Htet, Angel R. Gonzalez, Annette J. Dobson, Kavumpurathu Raman Thankappan, Hélène Delisle, Francisco J. Félix-Redondo, Ramón Suárez-Medina, Annika Rosengren, Sania Nishtar, Tanja G. M. Vrijkotte, Wolfgang Ahrens, Osvaldo Santos, Maria Cecília Formoso Assunção, Kazi M. Jamil, Stefano Marventano, Wenbin Wei, Norsyamlina Che Abdul Rahim, Shukri F. Mohamed, Bente Sparboe-Nilsen, Soon-Woo Park, Ana Isabel Rito, David Goltzman, W. M. Monique Verschuren, Catterina Ferreccio, Marta Buoncristiano, Ramón Alberto Rascón-Pacheco, Pradeep Joshi, Edward D Janus, Laetitia Huiart, Ala'a Alkerwi, Lorenza Pilotto, Mohannad Al Nsour, Daan Kromhout, Marius B. Bjertness, Oanh T. H. Trinh, Nico Dragano, Angélica Ochoa-Avilés, Ingunn Holden Bergh, Yuki Fujita, Juraci Almeida Cesar, Hajer Aounallah-Skhiri, Maria Dorobantu, Jordi Sunyer, Wolfgang Kratzer, Susanne R. de Rooij, Drude Molbo, Rebecca Goldsmith, Jean Woo, Mohammad El-khateeb, Tiffany K. Gill, Nish Chaturvedi, Benjamin Acosta-Cazares, Erik Lykke Mortensen, Nikhil D. Patel, Francesco Pistelli, Yuan He, Ivana Radic, Yi Zeng, Ilse Khouw, Reynaldo Martorell, Ching-Yu Cheng, Stine Schramm, Hana Shimizu-Furusawa, Jacek Jóźwiak, Radwan Qasrawi, Isti Ilmiati Fujiati, Charles Sossa Jérome, Ben Schöttker, Mikhail Benet, Anastasia Markaki, Christopher T. Cowell, Bharathi Viswanathan, Renata Kuciene, Jose Eugenio Lozano, Pedro J Ortiz, Delphine De Smedt, Elaine M. Murtagh, Kamel Ajlouni, Carlos A. Aguilar-Salinas, Graziella D'Arrigo, Xiangjun Wang, Lars Lind, Macia Enguerran, Marjeta Mišigoj-Duraković, Bo Werner, Jean-Michel Gaspoz, Kyungwon Oh, Seyed Rasoul Zakavi, Daniel Fernández-Bergés, Felix Kaducu, Ramon O. Jimenez, Jonathan E. Shaw, Nipa Rojroongwasinkul, Aicha Soumare, Astrid Petersmann, Tomasz Grodzicki, Parvina Mukhtorova, Eha Nurk, Bhawesh Koirala, Óscar Lopes, Ana Jelakovic, Karolina Milkowska, Magda Gasull, Regina Heidinger-Felso, Marcela González-Gross, Belong Cho, Daphne Mirkopoulou, Salvador Villalpando, Tran Quoc Bao, José Boggia, Daniela Galeone, Josep Redon, Matthias Bopp, Abbas Rezaianzadeh, Dusko Bjelica, Amir Houshang Mehrparvar, Felipe F. Casanueva, Khairil Si-Ramlee, Soheir H Ahmed, Maria Nordendahl, Luciana Zaccagni, Mahboubeh Parsaeian, Rod Jackson, Jorge Motta, Keiu Nelis, Fernando Rigo, Andrzej Pajak, Christa Meisinger, Clara Homs, Namuna Shrestha, Mar Alvarez-Pedrerol, Xun Tang, Johann Willeit, Motahareh Kheradmand, Jean Dallongeville, Jean-Bernard Ruidavets, Anne Tjønneland, Diana A. Santos, Lynne M. Boddy, Jie Hao, David Alejandro González-Chica, Elin Kolle, Jingli Gao, Małgorzata Mossakowska, Isabel O. Oliveira, Giuseppe Grosso, Seongjun Ha, Olfa Saidi, Albina A Fakhretdinova, Oye Gureje, Raluca Pop, Iulia Jurca Simina, Nuno Lunet, Maria Forsner, Peter Bjerregaard, Rachael McLean, Antonio Cabrera de León, Guy De Backer, José A. Casajús, Guang Ning, Emmanuella Magriplis, Laura Censi, Graziella Bruno, Valentina Peterkova, Angelique Chan, Yvonne T. van der Schouw, Charalambos Hadjigeorgiou, Anjani Kumar Jha, Toomas Veidebaum, Thamara Hubler Figueiró, Jana Kratenova, Michelle Cilia, Ivo Rakovac, Bill Stavreski, Ya Xing Wang, Oscar Noboa, Romana Roccaldo, Sara Magnacca, Johan Sundström, Peter Stehle, Tania Lopez, Francis Delpeuch, Julianne Williams, Ellisiv B. Mathiesen, Leanne M. Riley, Claudia M. Hormiga, Joanne Katz, Ekaterina Stoyanova, Heloisa Bettiol, Gabriele Nagel, Alireza Khosravi, Lars Bo Andersen, João Breda, Jørgen Meisfjord, Ahmad Faudzi Yusoff, Marjeta Majer, Robert Beaglehole, Caleb Ochimana, Shynar Abdrakhmanova, George S. Stergiou, Blanca Sandra Ruiz-Betancourt, Leon A. Simons, Eng Joo Tan, Victoria Farrugia Sant'Angelo, Gry Skodje, Maryam Keramati, Liv Elin Torheim, Seppo Koskinen, Assembekov Batyrbek, Jaakko Tuomilehto, Marjo-Riitta Järvelin, Ming-Hui Zhao, Krista Fischer, Tobias F. Rinke de Wit, Agnès Le Port, Reza Homayounfar, James E. Bennett, Yuna He, Matsuda Fumihiko, Qi Sheng You, Angela Spinelli, Scott B. McLean, Shirin Djalalinia, Thet Thet Mu, Yves Martin-Prével, Rafael N. Pichardo, Gailute Bernotiene, Pietro Amedeo Modesti, Frederick C. W. Wu, Chandini Nekkantti, Daniela Rodrigues, Tandi E. Matsha, Mihai Gafencu, Xingwang Ye, Salar Rahimikazerooni, Trevor S. Ferguson, Christophe Tzourio, Marie Zins, Fernando Rodríguez-Artalejo, Xu Ma, Elin Pettersen Sørgjerd, Lourdes Ribas-Barba, Nalan Uysal, Salim Berkinbayev, Enisa Kujundzic, Sari Voutilainen, Iraj Mohebbi, Heiner Boeing, Jorge Mota, Jana Námešná, Maria Tsigga, Zivka Dika, Gulmira Aitmurzaeva, Xu Lin, Valéria Regecová, Herman Schargrodsky, Stevo Popovic, Amelia C. Crampin, Hannu Uusitalo, André Luiz Sena Guimarães, Ali Esmaeili, Catherine Kyobutungi, Virginija Dulskiene, Diego Augusto Santos Silva, David De Ridder, Lizzy M. Brewster, Hashem Jaddou, Eunice Ugel, José Camolas, Azli Baharudin, Idris Guessous, Sok King Ong, Tabara Yasuharu, Ali Ghanbari, Anne W. Taylor, Iraj Nabipour, Justyna Godos, Cyrus Cooper, Bruna Gonçalves Cordeiro da Silva, Gonzalo Valdivia, Gyulli M. Kazakbaeva, Takuro Furusawa, Pawel Kurjata, Diego Vanuzzo, Marvin Cervantes-Loaiza, Karen Morgan, Mostafa Qorbani, Rute Santos, Marika Ferrari, Diego Salmerón, Ida Maria Schmidt, Gao Pei, Abu Am Hanif, Balkish M. Naidu, Maria Wany Louzada Strufaldi, Moesijanti Soekatri, Marcia Scazufca, Katharina Maruszczak, Jacqueline Ramke, Elvis Oa Wambiya, Kairit Mikkel, Napoleón Pérez-Farinós, Natalia Nowak-Szczepanska, Miao Li Chee, Jose Sanchez-Abanto, Rajaa Al-Raddadi, Michel Joffres, Vayia Rarra, Ningli Wang, Charmaine A. Duante, Sheikh Mohammed Shariful Islam, Manoli Garcia-de-la-Hera, Weili Yan, Dong Wook Shin, Rômulo Araújo Fernandes, Ilona Nenko, Sanjib Kumar Sharma, Alfonso Siani, Indrapal I. Meshram, Imelda A. Agdeppa, Ei Ei K. Nang, Ian Rouse, Avula Laxmaiah, Ana M. B. Menezes, Yih Chung Tham, Ebrahim Eftekhar, María José Tormo, Felicia Cañete, Marie Eliasen, Lutgart Braeckman, Dirk Vanderschueren, Genc Burazeri, Kari Kuulasmaa, Jesús Vioque, Marisa K. Sophiea, Agneta Sjöberg, Katarzyna Dereń, Albertino Damasceno, Jochanan Stessman, Stig E. Bojesen, Aline Meirhaeghe, Else Karin Grøholt, Flávio Danni Fuchs, Robert Lundqvist, Frédéric Gottrand, Jeongseon Kim, Helmut Schröder, Joanna Baran, Karina Mary de Paiva, Yousef Khader, Eric Monterrubio-Flores, Aneta Weres, Hans Concin, Damaskini Valvi, Sari Hantunen, Machi Suka, Elena Sacchini, Norbert Amougou, Ursula Kiechl-Kohlendorfer, Edwige Landais, Viktoria Anna Kovacs, Rosemarie Martin, Kenneth James, Amaneh Shayanrad, Grethe S. Tell, Norazizah Ibrahim Wong, Vedrana Sember, Anelise Reis Gaya, Konrad Jamrozik, Thorkild I. A. Sørensen, Martin Neovius, Urho M. Kujala, Nathalie Michels, Marcel Goldberg, Alexandra Cucu, Liliana Dacica, Adelheid Weber, Hermann Pohlabeln, Sandjaja, Jukka T. Salonen, Patricia Varona-Pérez, Tiina Laatikainen, Jolanta Słowikowska-Hilczer, Ana Paula Carlos Cândido, Julie Taylor, Anabela Mota-Pinto, Cora L. Craig, Teresa Shamah-Levy, María Dolores Chirlaque, Mohd Azahadi Omar, Dominique Cottel, Charumathi Sabanayagam, Andrea Gazzinelli, Mieczysław Litwin, Sadaf G. Sepanlou, Adolfo Rubinstein, Abbas Dehghan, Rildo de Souza Wanderley Júnior, Wenhua Zhao, Aleksandra Piwońska, Yong Tao, Bontha V. Babu, Marc J. Gunter, Harunobu Nakamura, Wojciech Drygas, Eiji Oda, Jia Li Duan, Stefan Söderberg, Anthony Kafatos, Lynell V Maniego, Els Clays, Wei-Yen Lim, Marshall K. Tulloch-Reid, Mariachiara Di Cesare, Mattias Johansson, Simona Costanzo, Margot González-León, Matthias Nauck, Henry Völzke, George Luiz Lins Machado-Coelho, Annette Peters, Rajiv T Erasmus, Juan Francisco Miquel, Andrea Gualtieri, Abdul Hamid Zargar, Kaare Christensen, Peter Willeit, Tanja Stocks, Christine Cameron, Samuel C. Dumith, Janina Petkeviciene, Boyd Swinburn, Magdalena Muc, Sabine Schipf, Tajana Zeljkovic Vrkic, Martin Bobak, Damian K Francis, Veronica Mocanu, Karien Stronks, Antonisamy Belavendra, Artur Mazur, Nagalla Balakrishna, Jardena J. Puder, Mehrdad Azmin, Shelly R. McFarlane, Sara Santos Sanz, Yang Yang, Anneke Blokstra, Rafel Ramos, Ertugrul Celikcan, Jody C Miller, Jesús Ibarluzea, Svetlana A. Shalnova, Maria Elisa Zapata, Guansheng Ma, Fereidoun Azizi, Beatriz D'Agord Schaan, Pedro Marques-Vidal, William A. Neal, Ana B. Crujeiras, Zhenyu Zhang, Naser Ahmadi, Abdullatif Husseini, Alun Evans, Jiang He, Edyta Łuszczki, Maria G. 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

23. Molecular screening of familial hypercholesterolemia in Icelanders

Author: Vilmundur Gudnason, Valur Emilsson, Oscar Puig, Matthew Akana, Rebecca Fox, Malgorzata Jaremko, Chihyu Chang, Ying Cai, Bolli Thorsson, Robert Wisotzkey, Michael Jansen, Greg Kellogg, Andrew Pollock, Elias F. Gudmundsson, and Bonny Patel
Subjects: 0301 basic medicine, Pediatrics, medicine.medical_specialty, Clinical Biochemistry, Iceland, Familial hypercholesterolemia, 030204 cardiovascular system & hematology, Monogenic disease, Hyperlipoproteinemia Type II, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Loss of Function Mutation, Medicine, Humans, Genetic Predisposition to Disease, Genetic Testing, Prospective Studies, Early onset, Genetic testing, Molecular screening, medicine.diagnostic_test, business.industry, Cholesterol, food and beverages, High-Throughput Nucleotide Sequencing, General Medicine, medicine.disease, Coronary heart disease, 030104 developmental biology, chemistry, Mutation, lipids (amino acids, peptides, and proteins), business
Abstract: Familial hypercholesterolemia (FH) is a monogenic disease characterized by a lifelong exposure to high LDL-C levels that can lead to early onset coronary heart disease (CHD). The main causes of FH identified to date include loss-of-function mutations in
Published: 2020

24. Antihypertensive medication uses and serum ACE2 levels: ACEIs/ARBs treatment does not raise serum levels of ACE2

Author: Valur, Emilsson, Elias F, Gudmundsson, Thor, Aspelund, Brynjolfur G, Jonsson, Alexander, Gudjonsson, Lenore J, Launer, Lori L, Jennings, Valborg, Gudmundsdottir, and Vilmundur, Gudnason
Subjects: cardiovascular diseases, hormones, hormone substitutes, and hormone antagonists, Article
Abstract: Importance Recent reports have shown that hypertension is the most common comorbidity associated with mortality in the current coronavirus disease 2019 (COVID-19). This has been related to the use of angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin II receptor blockers (ARBs) as animal studies indicate that these medications increase levels of ACE2, the cellular entry point for the coronavirus SARS-CoV-2. This has prompted clinicians to recommend discontinuing ACEIs and ARBs. Objective To examine the effect of ACEIs or ARBs treatment on serum levels of ACE2 and other key enzymes in the renin-angiotensin system (RAS). Design, Setting, and Participants A single center population-based study of 5457 Icelanders from the Age, Gene/Environment Susceptibility Reykjavik Study (AGES-RS) of the elderly (mean age 75±6 years) stratified by ACEIs (N = 699) or ARBs (N = 753) treatment. Main Outcomes and Measures The AGES-RS study population was stratified by ACEIs and ARBs medication use and compared for age, body mass index (BMI) (kg/m2), hypertension and type 2 diabetes (T2D) as well as serum levels of renin, ACE and ACE2. Results While renin and ACE levels were significantly raised in serum of individuals on ACEIs or ARBs treatments, the ACE2 levels remained unaffected. Conclusions and Relevance Treatment with ACEIs or ARBs does not raise ACE2 levels in serum. Therefore, the present study does not support the proposed discontinuation of these medications among patients affected with COVID-19.
Published: 2020

25. ACE2 levels are altered in comorbidities linked to severe outcome in COVID-19

Author: Vilmundur Gudnason, Brynjolfur G. Jonsson, Lori L. Jennings, Lenore J. Launer, Valborg Gudmundsdottir, Alexander Gudjonsson, Elias F. Gudmundsson, John Lamb, Thor Aspelund, and Valur Emilsson
Subjects: education.field_of_study, medicine.medical_specialty, Coronavirus disease 2019 (COVID-19), business.industry, Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), Population, Type 2 diabetes, Single Center, medicine.disease, Obesity, Coronary heart disease, Article, Internal medicine, medicine, education, business, Kidney disease
Abstract: AimsSeverity of outcome in COVID-19 is disproportionately higher among the obese, males, smokers, those suffering from hypertension, kidney disease, coronary heart disease (CHD) and/or type 2 diabetes (T2D). We examined if serum levels of ACE2, the cellular entry point for the coronavirus SARS-CoV-2, were altered in these high-risk groups.MethodsAssociations of serum ACE2 levels to hypertension, T2D, obesity, CHD, smokers and males in a single center population-based study of 5457 Icelanders from the Age, Gene/Environment Susceptibility Reykjavik Study (AGES-RS) of the elderly (mean age 75±6 years).ResultsSmokers, males, and individuals with T2D or obesity have altered serum levels of ACE2 that may influence productive infection of SARS-CoV-2 in these high-risk groups.ConclusionACE2 levels are upregulated in some patient groups with comorbidities linked to COVID-19 and as such may have an emerging role as outcome in COVID-19. a circulating biomarker for severity of severity of outcome in COVID-19.Key PointsQuestionSeverity of outcome in COVID-19 is disproportionately higher among the obese, males, smokers, those suffering from hypertension, kidney disease, coronary heart disease (CHD) and/or type 2 diabetes (T2D). Thus, we asked if the coronavirus SARS-CoV-2 receptor ACE2 was altered in the sera from these high-risk groups?FindingsIn a single center population-based study of 5457 Icelanders, the Age, Gene/Environment Susceptibility Reykjavik Study (AGES-RS), we find that ACE2 levels are significantly elevated in serum from smokers, obese and diabetic individuals, while reduced in males.MeaningThese results demonstrate that individuals with comorbidities associated with infection of SARS-CoV-2 in these individuals. severe outcome in COVID-19 have altered serum levels of ACE2 that may influence productive
Published: 2020

26. Coding and regulatory variants affect serum protein levels and common disease

Author: Nicholas M. Morton, Alexander Gudjonsson, Thor Aspelund, Elias F. Gudmundsson, Vilmundur Gudnason, Valur Emilsson, Mohd Anisul Karim, James R Staley, Brynjolfur G. Jonsson, Lenore J. Launer, Marjan Ilkov, John Lamb, Jan H.N. Lindeman, Valborg Gudmundsdottir, and Lori L. Jennings
Subjects: Genetics, Common disease, Cohort, Complex disease, Serum protein, medicine, Cancer, Biology, Affect (psychology), medicine.disease, Blood proteins, Exome
Abstract: Circulating proteins are prognostic for human outcomes including cancer, heart failure, brain trauma and brain amyloid plaque burden. A deep serum proteome survey recently revealed close associations of serum protein networks and common diseases. The present study reveals unprecedented number of individual serum proteins that overlap genetic signatures of diseases emanating from different tissues of the body. Here, 54,469 low-frequency and common exome-array variants were compared with 4782 protein measurements in the serum of 5343 individuals of the deeply annotated AGES Reykjavik cohort. Using a study-wide significant threshold, 2019 independent exome array variants affecting levels of 2135 serum proteins were identified. These variants overlapped genetic loci for hundreds of complex disease traits, emphasizing the emerging role for serum proteins as biomarkers of and potential causative agents of multiple diseases.
Published: 2020

27. Circulating protein signatures and causal candidates for type 2 diabetes

Author: Vilmundur Gudnason, Lori L Jennings, Karsten Suhre, John R Lamb, Nuno R Zilhão, Stefan M Jonsson, Elias F Gudmundsson, Marjan Ilkov, Thor Aspelund, Valur Emilsson, Shaza B Zaghlool, Valborg Gudmundsdottir, and Ada Admin
Abstract: The increasing prevalence of type 2 diabetes poses a major challenge to societies worldwide. Blood-based factors like serum proteins are in contact with every organ in the body to mediate global homeostasis and may thus directly regulate complex processes such as aging and the development of common chronic diseases. We applied a data-driven proteomics approach, measuring serum levels of 4,137 proteins in 5,438 elderly Icelanders and identified 536 proteins associated with prevalent and/or incident type 2 diabetes. We validated a subset of the observed associations in an independent case-control study of type 2 diabetes. These protein associations provide novel biological insights into the molecular mechanisms that are dysregulated prior to and following the onset of type 2 diabetes and can be detected in serum. A bi-directional two-sample Mendelian randomization analysis indicated that serum changes of at least 23 proteins are downstream of the disease or its genetic liability, while 15 proteins were supported as having a causal role in type 2 diabetes.
Published: 2020

28. A pooled-analysis of age and sex based coronary artery calcium scores percentiles

Author: Vilmundur Gudnason, Aeilko H. Zwinderman, Paulo A. Lotufo, Elias F. Gudmundsson, Maurice W J de Ronde, Paolo Raggi, Bruce Cooil, Isabela M. Benseñor, Sara-Joan Pinto-Sietsma, Thor Aspelund, Matthew J. Budoff, S. Matthijs Boekholdt, Yuki Ohmoto-Sekine, Mariette Biemond, R. Nils Planken, Amir M. Khoshiwal, Gastroenterology and Hepatology, Graduate School, Radiology and Nuclear Medicine, ACS - Pulmonary hypertension & thrombosis, Cardiology, ACS - Atherosclerosis & ischemic syndromes, Epidemiology and Data Science, APH - Methodology, and ACS - Heart failure & arrhythmias
Subjects: Adult, Male, Percentile, Computed Tomography Angiography, Population, MEDLINE, Coronary Artery Disease, 030204 cardiovascular system & hematology, Percentile nomogram, Coronary Angiography, Asymptomatic, 030218 nuclear medicine & medical imaging, Coronary artery disease, 03 medical and health sciences, 0302 clinical medicine, Age Distribution, Sex Factors, Predictive Value of Tests, Risk Factors, Multidetector Computed Tomography, medicine, Humans, Radiology, Nuclear Medicine and imaging, cardiovascular diseases, Sex Distribution, education, Vascular Calcification, Computed tomography, Aged, Aged, 80 and over, education.field_of_study, business.industry, Age Factors, nutritional and metabolic diseases, Nomogram, Middle Aged, medicine.disease, Calcium score, Race Factors, Nomograms, Sample size determination, Female, medicine.symptom, Cardiology and Cardiovascular Medicine, business, Risk assessment, Demography
Abstract: Background Age and sex based coronary artery calcium score (CAC) percentiles have been used to improve coronary artery disease (CAD) risk prediction. However, the main limitation of the CACs percentiles currently in use is that they are often based on single studies. We performed a pooled analysis of all available studies that reported on CAC percentiles, in order to develop more generalizable age and sex nomograms. Methods PubMed/Medline and Embase were searched for studies that reported nomograms of age and sex-based CACs percentiles. Studies were included if they reported data collected among asymptomatic individuals without a history of cardiovascular disease. Absolute CACs for each specific percentile stratum were pooled and new percentiles were generated taking into account the sample size of the study. Results We found 831 studies, of which 12 met the inclusion criteria. Data on CACs percentiles of 134,336 Western and 33,488 Asians were pooled separately, rendering a weighted CACs percentile nomogram available at https://www.calciumscorecalculator.com . Our weighted percentiles differed by up to 24% from the nomograms in use today. Conclusions Our pooled age and sex based CACs percentiles based on over 155,000 individuals should provide a measure of risk that is more applicable to a wider population than the ones currently in use and hopefully will lead to better risk assessment and treatment decisions.
Published: 2020

29. The risk of developing a mismatch repair deficient colorectal cancer after undergoing cholecystectomy

Author: Thor Aspelund, Jon G. Jonasson, Matthías Halldórsson, Michael Hauptmann, Sigurdis Haraldsdottir, Kristín Huld Haraldsdóttir, Vilmundur Gudnason, Petur Snaebjornsson, and Elias F. Gudmundsson
Subjects: Male, congenital, hereditary, and neonatal diseases and abnormalities, Colorectal cancer, DNA repair, medicine.medical_treatment, Iceland, MLH1, DNA Mismatch Repair, Risk Assessment, 03 medical and health sciences, 0302 clinical medicine, medicine, Humans, Cholecystectomy, Epigenetics, neoplasms, Gene, Aged, Aged, 80 and over, business.industry, Gastroenterology, Microsatellite instability, Middle Aged, medicine.disease, Immunohistochemistry, digestive system diseases, Logistic Models, Case-Control Studies, 030220 oncology & carcinogenesis, Cancer research, Female, Microsatellite Instability, 030211 gastroenterology & hepatology, DNA mismatch repair, Colorectal Neoplasms, business
Abstract: Mismatch repair deficient (dMMR) colorectal cancer (CRC) is caused by inactivation of the MMR DNA repair system, most commonly via epigenetic inactivation of the MLH1 gene, and these tumors occur most frequently in the right colon. The objective was to determine whether cholecystectomy (CCY) increases the risk of a dMMR CRC by comparing CCY incidence in patients with dMMR CRC and proficient MMR (pMMR) CRC to unaffected controls.All patients diagnosed with CRC in Iceland from 2000 to 2009 (n = 1171) were included. They had previously been screened for dMMR by immunohistochemistry (n = 129 were dMMR). Unaffected age- and sex-matched controls (n = 17,460) were obtained from large Icelandic cohort studies. Subjects were cross-referenced with all pathology databases in Iceland to establish who had undergone CCY. Odds ratios were calculated using unconditional logistic regression.Eighteen (13.7%) dMMR CRC cases and 90 (8.7%) pMMR CRC cases had undergone CCY compared to 1532 (8.8%) controls. CCY-related odds ratios (OR) were 1.06 (95% CI 0.90-1.26, p = .577) for all CRC, 1.16 (95% CI 0.66-2.05 p = .602) for dMMR CRCand 1.04 (95% CI 0.83-1.29, p = .744) for pMMR CRC. Furthermore, OR for dMMR CRC was 0.51 (95% CI 0.16-1.67, p = .266), 2.04 (95% CI 0.92-4.50, p = .080) and 1.08 (95% CI 0.40-2.89, p = .875) 10 years, 10-20 years and 20 years after a CCY, respectively.There was no evidence of increased risk of developing dMMR CRC after CCY although a borderline significantly increased 2-fold risk was observed 10-20 years after CCY. Larger studies are warranted to examine this further.
Published: 2018

30. Circulating Protein Signatures and Causal Candidates for Type 2 Diabetes

Author: Elias F. Gudmundsson, Nuno R. Zilhão, Lori L. Jennings, Valur Emilsson, Stefan M Jonsson, Vilmundur Gudnason, Shaza B. Zaghlool, Valborg Gudmundsdottir, Marjan Ilkov, John Lamb, Thor Aspelund, and Karsten Suhre
Subjects: 0301 basic medicine, Male, Genotype, Endocrinology, Diabetes and Metabolism, 030209 endocrinology & metabolism, Type 2 diabetes, Disease, Proteomics, Bioinformatics, Polymorphism, Single Nucleotide, 03 medical and health sciences, 0302 clinical medicine, Polymorphism (computer science), Diabetes mellitus, Internal Medicine, medicine, Humans, Genetic Predisposition to Disease, Aged, Aged, 80 and over, business.industry, Case-control study, Mendelian Randomization Analysis, Genetics/Genomes/Proteomics/Metabolomics, medicine.disease, Blood proteins, 030104 developmental biology, Diabetes Mellitus, Type 2, Case-Control Studies, Female, business
Abstract: The increasing prevalence of type 2 diabetes poses a major challenge to societies worldwide. Blood-based factors like serum proteins are in contact with every organ in the body to mediate global homeostasis and may thus directly regulate complex processes such as aging and the development of common chronic diseases. We applied a data-driven proteomics approach, measuring serum levels of 4,137 proteins in 5,438 elderly Icelanders, and identified 536 proteins associated with prevalent and/or incident type 2 diabetes. We validated a subset of the observed associations in an independent case-control study of type 2 diabetes. These protein associations provide novel biological insights into the molecular mechanisms that are dysregulated prior to and following the onset of type 2 diabetes and can be detected in serum. A bidirectional two-sample Mendelian randomization analysis indicated that serum changes of at least 23 proteins are downstream of the disease or its genetic liability, while 15 proteins were supported as having a causal role in type 2 diabetes.
Published: 2019

31. Deep serum proteomics reveal biomarkers and causal candidates for type 2 diabetes

Author: John Lamb, Marjan Ilkov, Thor Aspelund, Elias F. Gudmundsson, Vilmundur Gudnason, Valur Emilsson, Valborg Gudmundsdottir, Nuno R. Zilhão, and Lori L. Jennings
Subjects: Serum proteomics, endocrine system diseases, business.industry, Type 2 Diabetes Mellitus, Mendelian Randomization Analysis, Computational biology, Type 2 diabetes, Proteomics, Precision medicine, Logistic regression, medicine.disease, Blood proteins, Medicine, business
Abstract: The prevalence of type 2 diabetes mellitus (T2DM) is expected to increase rapidly in the next decades, posing a major challenge to societies worldwide. The emerging era of precision medicine calls for the discovery of biomarkers of clinical value for prediction of disease onset, where causal biomarkers can furthermore provide actionable targets. Blood-based factors like serum proteins are in contact with every organ in the body to mediate global homeostasis and may thus directly regulate complex processes such as aging and the development of common chronic diseases. We applied a data-driven proteomics approach measuring serum levels of 4,137 proteins in 5,438 Icelanders to discover novel biomarkers for incident T2DM and describe the serum protein profile of prevalent T2DM. We identified 536 proteins associated with incident or prevalent T2DM. Through LASSO penalized logistic regression analysis combined with bootstrap resampling, a panel of 20 protein biomarkers that accurately predicted incident T2DM was identified with a significant incremental improvement over traditional risk factors. Finally, a Mendelian randomization analysis provided support for a causal role of 48 proteins in the development of T2DM, which could be of particular interest as novel therapeutic targets.
Published: 2019
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32. Traction Bronchiectasis/Bronchiolectasis is Associated with Interstitial Lung Abnormality Mortality

Author: Elias F. Gudmundsson, David A. Lynch, Tetsuro Araki, Hiroto Hatabu, Noriyuki Tomiyama, George R. Washko, Yoshitake Yamada, Rachel K. Putman, Gary M. Hunninghake, Gunnar Gudmundsson, Masahiro Yanagawa, Takuya Hino, David C. Christiani, Raúl San José Estépar, Vladimir I. Valtchinov, Masahiro Jinzaki, Takeshi Johkoh, Akinori Hata, Osamu Honda, Tomoyuki Hida, Vilmundur Gudnason, Hiroshi Honda, Mizuki Nishino, and Junwei Lu
Subjects: Male, medicine.medical_specialty, Iceland, Severity of Illness Index, Gastroenterology, Article, 030218 nuclear medicine & medical imaging, Cohort Studies, 03 medical and health sciences, 0302 clinical medicine, Usual interstitial pneumonia, Internal medicine, Pulmonary fibrosis, medicine, Humans, Radiology, Nuclear Medicine and imaging, Longitudinal Studies, Honeycombing, Traction bronchiectasis, Lung, Aged, Proportional Hazards Models, Aged, 80 and over, Bronchiectasis, business.industry, Proportional hazards model, General Medicine, medicine.disease, Survival Analysis, medicine.anatomical_structure, 030220 oncology & carcinogenesis, Female, Abnormality, Lung Diseases, Interstitial, Tomography, X-Ray Computed, business
Abstract: PURPOSE: To investigate if the presence and severity of traction bronchiectasis/bronchiolectasis are associated with poorer survival in subjects with ILA. METHOD: The study included 3,594 subjects (378 subjects with ILA and 3,216 subjects without ILA) in AGES-Reykjavik Study. Chest CT scans of 378 subjects with ILA were evaluated for traction bronchiectasis/bronchiolectasis, defined as dilatation of bronchi/bronchioles within areas demonstrating ILA. Traction bronchiectasis/bronchiolectasis Index (TBI) was assigned as: TBI=0, ILA without traction bronchiectasis/bronchiolectasis: TBI=1, ILA with bronchiolectasis but without bronchiectasis or architectural distortion: TBI=2, ILA with mild to moderate traction bronchiectasis: TBI=3, ILA and severe traction bronchiectasis and/or honeycombing. Overall survival (OS) was compared among the subjects in different TBI groups and those without ILA. RESULTS: The median OS was 12.93 years (95%CI; 12.67 – 13.43) in the subjects without ILA; 11.95 years (10.03 – not reached) in TBI-0 group; 8.52 years (7.57 – 9.30) in TBI-1 group; 7.63 years (6.09 – 9.10) in TBI-2 group; 5.40 years (1.85 – 5.98) in TBI-3 group. The multivariable Cox models demonstrated significantly shorter OS of TBI-1, TBI-2, and TBI-3 groups compared to subjects without ILA (P
Published: 2020

33. The Associations of Interstitial Lung Abnormalities with Cancer Diagnoses and Mortality

Author: Hiroto Hatabu, Gunnar Gudmundsson, Elias F. Gudmundsson, Vilmundur Gudnason, Gary M. Hunninghake, Gisli Thor Axelsson, Thor Aspelund, Mizuki Nishino, Tetsuro Araki, Rachel K. Putman, and Tomayuki Hida
Subjects: Adult, Pulmonary and Respiratory Medicine, Oncology, medicine.medical_specialty, Lung Neoplasms, Population, Iceland, Article, 03 medical and health sciences, Idiopathic pulmonary fibrosis, 0302 clinical medicine, Internal medicine, medicine, Humans, Cumulative incidence, 030212 general & internal medicine, Risk factor, Lung cancer, education, Lung, Early Detection of Cancer, Proportional Hazards Models, education.field_of_study, business.industry, Cancer, respiratory system, medicine.disease, respiratory tract diseases, medicine.anatomical_structure, 030228 respiratory system, Tomography, X-Ray Computed, business, Lung cancer screening
Abstract: An increased incidence of lung cancer is well-known among patients with idiopathic pulmonary fibrosis. It is unknown whether interstitial lung abnormalities, early fibrotic changes of the lung, are a risk factor for lung cancer in the general population.The study's objective was to assess whether interstitial lung abnormalities were associated with diagnoses of, and mortality from, lung cancer and other cancers. Data from the AGES-Reykjavik study, a cohort of 5764 elderly Icelanders, were used. Outcome data were ascertained from electronic medical records. Gray's tests, Cox proportional hazards models and proportional subdistribution hazards models were used to analyse associations of interstitial lung abnormalities with lung cancer diagnoses and lung cancer mortality as well as diagnoses and mortality from all cancers.Participants with interstitial lung abnormalities had greater cumulative incidence of lung cancer diagnoses (pPeople with interstitial lung abnormalities are at increased risk of lung cancer and lung cancer mortality, but not of other cancers. This implies that an association between fibrotic and neoplastic lung diseases of the lung exists from the early stages of lung fibrosis and suggests interstitial lung abnormalities as a risk factor in lung cancer screening efforts.
Published: 2020

34. Molecular Screening of Familial Hypercholesterolemia in the Icelandic Population

Author: Valur Emilsson, Greg Kellogg, Bonny Patel, Rebecca Fox, Malgorzata Jaremko, Vilmundur Gudnason, Ying Cai, Bolli Thorsson, Matthew Akana, Robert Wisotzkey, Michael Jansen, Chihyu Chang, Oscar Puig, Andrew Pollock, and Elias F. Gudmundsson
Subjects: education.field_of_study, Apolipoprotein B, biology, medicine.diagnostic_test, Molecular screening, business.industry, PCSK9, Population, Familial hypercholesterolemia, Bioinformatics, medicine.disease, Culprit, LDL receptor, biology.protein, medicine, education, business, Genetic testing
Abstract: Familial hypercholesterolemia (FH) is a monogenic disease characterized by a lifelong exposure to high LDL-C levels that can lead to early onset coronary heart disease (CHD). The main causes of FH identified to date include loss-of-function mutations in LDLR or APOB, or gain-of-function mutations in PCSK9. Early diagnosis and genetic testing of FH suspects is critical for improved prognosis of affected individuals as lipid lowering treatments are effective in preventing CHD related morbidity and mortality. In the present manuscript, we developed a comprehensive next generation sequencing (NGS) panel which we applied on two different resources of FH in the Icelandic population: 62 subjects from 23 FH families with known or unknown culprit mutations, and a population-based sampling of 315 subjects selected for total cholesterol levels above the 95th percentile cut-point. The application of the NGS panel revealed significant diagnostic yields in identifying pathogenic LDLR mutations in both family and population-based genetic testing.
Published: 2018
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35. Associations of interstitial lung abnormalities with physical function measures

Author: Ezra R. Miller, Gary M. Hunninghake, Vilmundur Gudnason, Gunnar Gudmundsson, Hiroto Hatabu, Kristin Siggeirsdottir, Tetsuro Araki, Rachel K. Putman, Gudny Eiriksdottir, Tamara B. Harris, Sigurdur Sigurdsson, Elias F. Gudmundsson, Lenore J. Launer, Gisli Thor Axelsson, and Thor Aspelund
Subjects: medicine.medical_specialty, Lung, business.industry, Physical function, medicine.disease, Logistic regression, Grip strength, medicine.anatomical_structure, Fibrosis, Internal medicine, Pulmonary fibrosis, medicine, Cardiology, Stage (cooking), business, Cohort study
Abstract: Interstitial lung abnormalities (ILA) are radiological features resembling an early stage of pulmonary fibrosis. ILA has been associated with many risks factors of fibrosis, as well as increased mortality, poorer subjectively assessed health and reduced exercise capacity. It remains unclear whether ILA is related to reductions in a wider range of physical capabilities. The aim of the study was to find out whether objective measures of physical function were associated with ILA. Data from the AGES-Reykjavik study, an Icelandic cohort study of 5,764 elderly men and women, were used. ILA status was assessed from thoracic CT scans. Objective measurements of five measures of physical function were used; grip strength, knee extension strength, the timed-up-and-go test, usual gait speed and thigh muscle mass. Associations of these markers with ILA were explored using logistic regression modelling adjusting for relevant covariates. Four measures of physical function were significantly associated with increased ILA risk. These measures were grip strength (OR=1.21 per a reduction of 100 N, p-value=0.024), knee extension strength (OR=1.23 per a reduction of 100 N, p-value=0.0036), usual gait speed (OR=1.06 per a test time increase of 1 second, p-value=0.026), and thigh muscle mass (OR=1.14 per a reduction of 10 cm2, p-value=0.0008). In the study, reductions in objective measures of physical function were associated with an increased risk of interstitial lung abnormalities. These novel findings indicate that ILA is related to a greater spectrum of physical decline than previously thought and have implications for further research.
Published: 2018

36. Interstitial lung abnormalities and physical function

Author: Vilmundur Gudnason, Gary M. Hunninghake, Rachel K. Putman, Tamara B. Harris, Kristin Siggeirsdottir, Hiroto Hatabu, Lenore J. Launer, Gisli Thor Axelsson, Elias F. Gudmundsson, Gunnar Gudmundsson, Thor Aspelund, Sigurdur Sigurdsson, Gudny Eiriksdottir, Tetsuro Araki, and Ezra R. Miller
Subjects: Pulmonary and Respiratory Medicine, Pathology, medicine.medical_specialty, Lung, business.industry, Original Research Letters, MEDLINE, respiratory system, Physical function, 3. Good health, 03 medical and health sciences, 0302 clinical medicine, Text mining, medicine.anatomical_structure, 030228 respiratory system, medicine, 030212 general & internal medicine, business
Abstract: The term interstitial lung abnormalities (ILA) was coined to define a precursory stage of idiopathic pulmonary fibrosis and encompasses a set of radiological changes seen in interstitial lung diseases (ILD) but are often of lesser magnitude [1]. ILA have been associated with age, many environmental and genetic risk factors and pulmonary symptoms of idiopathic pulmonary fibrosis [1, 2]. ILA have also been associated with reduced exercise capacity and self-reported health and function [3–5]., Reductions in objectively measured physical function are associated with interstitial lung abnormalities http://ow.ly/azAW30kMhqv
Published: 2018

37. Population distribution of traditional and the emerging cardiovascular risk factors carotid plaque and IMT : The REFINE-Reykjavik study with comparison with the Tromsø study

Author: Gudny Eiriksdottir, Ellisiv B. Mathiesen, Bolli Thorsson, Vilmundur Gudnason, Kjell Arne Arntzen, Thor Aspelund, Sigurdur Sigurdsson, M. L. Bots, Elias F. Gudmundsson, Læknadeild (HÍ), Faculty of Medicine (UI), Heilbrigðisvísindasvið (HÍ), School of Health Sciences (UI), Háskóli Íslands, and University of Iceland
Subjects: Carotid Artery Diseases, Male, Carotid arteries, Iceland, Disease, Cardiovascular Medicine, 030204 cardiovascular system & hematology, Carotid Intima-Media Thickness, Body Mass Index, 0302 clinical medicine, Risk Factors, Epidemiology, Prevalence, 030212 general & internal medicine, VDP::Medisinske Fag: 700::Klinisk medisinske fag: 750::Kardiologi: 771, Aged, 80 and over, Medicine(all), education.field_of_study, Kransæðasjúkdómar, Norway, General Medicine, ultrasonography, Middle Aged, Plaque, Atherosclerotic, Ómskoðun, Carotid Arteries, Cardiovascular Diseases, Female, epidemiology, Adult, medicine.medical_specialty, Cardiovascular risk factors, Population, 03 medical and health sciences, Sex Factors, Internal medicine, medicine, Humans, coronary heart disease, education, Aged, VDP::Medical disciplines: 700::Clinical medical disciplines: 750::Cardiology: 771, Faraldsfræði, business.industry, Research, Atherosclerosis, Blood pressure, business, Body mass index
Abstract: Publisher's version (útgefin grein)., Objectives Population statistics for carotid plaque and cardiovascular risk factors reported in scientific journals are usually presented as averages for the population or age and sex adjusted, rather than sex and age groups. Important population differences about atherosclerosis and cardiovascular risk factors may thus be missed. We compare the distribution of cardiovascular risk factors, carotids plaque and carotid intima-media thickness (CIMT) in two population-based studies. Methods Carotid artery atherosclerotic plaque prevalence and risk factors levels for cardiovascular disease by sex in 5-year age groups from the Risk Evaluation For Infarct Estimates Reykjavik study (REFINE-Reykjavik study) were compared with data from the Tromsø 6 study. Results The threshold of carotid plaque presence in the Tromsø 6 study fell between minimal and moderate plaque defined in the REFINE-Reykjavik study reflecting carotid plaque prevalence. The prevalence of minimal carotid plaque in the REFINE-Reykjavik study was 47% in men (40-69 years old) and 38% in women and 11% in men and 7% in women of moderate plaque. The prevalence of any plaque in the Tromsø 6 study was 35% in men and 27% in women. The mean (CIMT) was similar in the studies. In the Tromsø 6 study mean systolic blood pressure was 8 mm Hg higher in men and 10 mm Hg higher in women, mean low-density lipoprotein was 0.5 mmol/L higher in men and 0.3 mmol/L higher in women and the prevalence of smoking was 4% higher in men and 9% higher in women. However, body mass index was 0.8 kg/m 2 higher in men and 0.9 kg/m 2 in women in the REFINE-Reykjavik study. Conclusion Comparison between Iceland and Norway revealed differences in the prevalence of carotid plaque, which was assumed to be due to different definition of plaque. However, clinically significant differences in conventional cardiovascular risk factors were seen. This underscores the importance of detailed comparison of population data across different populations., The authors would like to thank the participants in the REFINE-Reykjavik study for their valuable contribution. Contributors: Conception and design of study: BT, VG, TA, SS and GE; acquisition of data: BT, SS, EFG, KAA and EBM; analysis and/or interpretation of data: all authors; drafting the manuscript: BT, GE, SS, TA and VG; revising the manuscript critically for important intellectual content: GE, SS, MLB, TA, EBM and VG. All authors approved of the version of the manuscript to be published. Funding: This work was supported by grants from RANNÍS (The Icelandic Centre for Research 090452) and Hjartavernd (Icelandic Heart Association).
Published: 2018

38. Interstitial lung abnormalities and self-reported health and functional status

Author: Ezra R. Miller, Rachel K. Putman, Elias F. Gudmundsson, Sigurdur Sigurdsson, Vilmundur Gudnason, Tetsuro Araki, Tamara B. Harris, Hiroto Hatabu, Gunnar Gudmundsson, Gisli Thor Axelsson, Gudny Eiriksdottir, Gary M. Hunninghake, Lenore J. Launer, and Thor Aspelund
Subjects: Pulmonary and Respiratory Medicine, Male, medicine.medical_specialty, Activities of daily living, Health Status, Physical activity, Logistic regression, Article, 03 medical and health sciences, Idiopathic pulmonary fibrosis, 0302 clinical medicine, Internal medicine, Activities of Daily Living, Medicine, Humans, 030212 general & internal medicine, Self report, Exercise, Aged, Lung, business.industry, Reproducibility of Results, medicine.disease, medicine.anatomical_structure, Logistic Models, 030228 respiratory system, Functional status, Female, General health, Self Report, business, Lung Diseases, Interstitial
Abstract: We investigated the association between interstitial lung abnormalities (ILA) and self-reported measures of health and functional status in 5764 participants from the Age, Gene/Environment Susceptibility-Reykjavik study. The associations of ILA to activities of daily living (ADLs), general health status and physical activity were explored using logistic regression models. Participants with ILA were less likely to be independent in ADLs (OR 0.70; 95% CI 0.55 to 0.90) to have good or better self-reported health (OR 0.66; 95% CI 0.52 to 0.82) and to participate in physical activity (OR 0.72; CI 0.56 to 0.91). The results demonstrate ILA’s association with worsening self-reported health and functional status.
Published: 2018

39. Co-regulatory networks of human serum proteins link genetics to disease

Author: Elias F. Gudmundsson, Jun Zhu, Rebecca Pitts, Xia Yang, Tamara B. Harris, Lori L. Jennings, Orn Olafsson, Marjan Ilkov, Vladimir Trifonov, Valur Emilsson, Vilmundur Gudnason, Lenore J. Launer, Anthony P. Orth, Le Shu, Jia Zhang, John Lamb, Sigurdur Sigurdsson, Valborg Gudmundsdottir, Jeremy To, Thor Aspelund, Gudny Eiriksdottir, Scott A. Lesley, Andrei Manolescu, Johanna Jakobsdottir, Bin Zhang, Shane R. Horman, Heather Hoover, and Nancy Finkel
Subjects: 0301 basic medicine, Pairwise correlation, Proteomics, Extracellular proteins, Proteome, Complex disease, Iceland, Disease, Biology, Article, 03 medical and health sciences, 0302 clinical medicine, Metabolic Diseases, Genetic variation, Humans, Genetic Predisposition to Disease, Metabolic disease, Protein modules, Genetics, Multidisciplinary, Genetic Variation, Blood Proteins, Aptamers, Nucleotide, Blood proteins, Blood, 030104 developmental biology, Cardiovascular Diseases, 030217 neurology & neurosurgery, Metabolic Networks and Pathways
Abstract: The blood proteome in disease Understanding the function of human blood serum proteins in disease has been limited by difficulties in monitoring their production, accumulation, and distribution. Emilsson et al. investigated human serum proteins of more than 5000 Icelanders over the age of 65. The composition of blood serum includes a complex regulatory network of proteins that are globally coordinated across most or all tissues. The authors identified modules and functional groups associated with disease and health outcomes and were able to link genetic variants to complex diseases. Science , this issue p. 769
Published: 2017

40. Incidence of Brain Infarcts, Cognitive Change, and Risk of Dementia in the General Population The AGES-Reykjavik Study (Age Gene/Environment Susceptibility-Reykjavik Study)

Author: Sigurdur Sigurdsson, Elias F. Gudmundsson, Thor Aspelund, Vilmundur Gudnason, Lenore J. Launer, P.V. Jonsson, Mark A. van Buchem, Olafur Kjartansson, Maria K. Jonsdottir, and Gudny Eiriksdottir
Subjects: Brain Infarction, Male, cognition, medicine.medical_specialty, Population, Iceland, Neuropsychological Tests, 030204 cardiovascular system & hematology, Article, 03 medical and health sciences, 0302 clinical medicine, cohort studies, Cerebellum, Internal medicine, medicine, Humans, Dementia, Cognitive Dysfunction, Longitudinal Studies, cardiovascular diseases, Cognitive decline, Psychiatry, education, Stroke, Aged, risk, Aged, 80 and over, Cerebral Cortex, Advanced and Specialized Nursing, education.field_of_study, business.industry, Incidence (epidemiology), medicine.disease, Magnetic Resonance Imaging, Confidence interval, Relative risk, cardiovascular system, Cardiology, incidence, Female, Neurology (clinical), Cardiology and Cardiovascular Medicine, business, 030217 neurology & neurosurgery, Cohort study, dementia
Abstract: Background and Purpose— The differentiation of brain infarcts by region is important because their cause and clinical implications may differ. Information on the incidence of these lesions and association with cognition and dementia from longitudinal population studies is scarce. We investigated the incidence of infarcts in cortical, subcortical, cerebellar, and overall brain regions and how prevalent and incident infarcts associate with cognitive change and incident dementia. Methods— Participants (n=2612, 41% men, mean age 74.6±4.8) underwent brain magnetic resonance imaging for the assessment of infarcts and cognitive testing at baseline and on average 5.2 years later. Incident dementia was assessed according to the international guidelines. Results— Twenty-one percent of the study participants developed new infarcts. The risk of incident infarcts in men was higher than the risk in women (1.8; 95% confidence interval, 1.5–2.3). Persons with both incident and prevalent infarcts showed steeper cognitive decline and had almost double relative risk of incident dementia (1.7; 95% confidence interval, 1.3–2.2) compared with those without infarcts. Persons with new subcortical infarcts had the highest risk of incident dementia compared with those without infarcts (2.6; 95% confidence interval, 1.9–3.4). Conclusions— Men are at greater risk of developing incident brain infarcts than women. Persons with incident brain infarcts decline faster in cognition and have an increased risk of dementia compared with those free of infarcts. Incident subcortical infarcts contribute more than cortical and cerebellar infarcts to incident dementia which may indicate that infarcts of small vessel disease origin contribute more to the development of dementia than infarcts of embolic origin in larger vessels.
Published: 2017

41. Vitamin D and mortality: Individual participant data meta-analysis of standardized 25-hydroxyvitamin D in 26916 individuals from a European consortium

Author: Christopher T. Sempos, Stefan Pilz, Lars Rejnmark, Thor Aspelund, Tom Wilsgaard, Kirsten G. Dowling, Femke Rutters, Ragnar Martin Joakimsen, Natasja M. van Schoor, Winfried März, Maja-Lisa Løchen, Paul Lips, Kevin D. Cashman, Giel Nijpels, Ellisiv B. Mathiesen, Zuzana Škrabáková, Ramon Durazo-Arvizu, Vilmundur Gudnason, Martin Gaksch, Inger Njølstad, Esther van 't Riet, Mairead Kiely, Michael Thamm, Karin M. A. Swart, Diana Grove-Laugesen, Henrik Schirmer, Christa Scheidt-Nave, Ingeborg A. Brouwer, Tamara B. Harris, Marcus E. Kleber, Elias F. Gudmundsson, Gert B. M. Mensink, Guri Grimnes, Markus A. Busch, Gudny Eiriksdottir, Rolf Jorde, Andreas Tomaschitz, Mary Frances Cotch, Jacqueline M. Dekker, Martin R. Grübler, Joline W.J. Beulens, Epidemiology and Data Science, APH - Health Behaviors & Chronic Diseases, General practice, APH - Societal Participation & Health, APH - Aging & Later Life, Internal medicine, APH - Personalized Medicine, ACS - Diabetes & metabolism, ACS - Heart failure & arrhythmias, Læknadeild (HÍ), Faculty of Medicine (UI), Heilbrigðisvísindasvið (HÍ), School of Health Sciences (UI), Háskóli Íslands, University of Iceland, Nutrition and Health, and APH - Mental Health
Subjects: Gerontology, Male, Dánartíðni, D vítamín, Organic chemistry, lcsh:Medicine, Blood Pressure, Cardiovascular Medicine, Vascular Medicine, Cohort Studies, 0302 clinical medicine, Mathematical and Statistical Techniques, Endocrinology, Medicine and Health Sciences, 030212 general & internal medicine, Prospective Studies, Blóðrásarsjúkdómar, Vitamin D, Prospective cohort study, lcsh:Science, 2. Zero hunger, education.field_of_study, Public health, Multidisciplinary, Death rates, VDP::Medical disciplines: 700::Clinical medical disciplines: 750, Mortality rate, Hazard ratio, VDP::Medisinske Fag: 700::Klinisk medisinske fag: 750, Vitamins, Middle Aged, Reference Standards, 3. Good health, Europe, Survival Rate, Physical sciences, Chemistry, Nutritional deficiencies, Cardiovascular diseases, Cardiovascular Diseases, Research Design, Hypertension, Deficiency, Female, Statistics (Mathematics), Research Article, medicine.medical_specialty, Death Rates, Endocrine Disorders, Population, 030209 endocrinology & metabolism, Research and Analysis Methods, vitamin D deficiency, 03 medical and health sciences, Chemical compounds, SDG 3 - Good Health and Well-being, Internal medicine, Organic compounds, medicine, Vitamin D and neurology, Diabetes Mellitus, Journal Article, Humans, Risk factor, Statistical Methods, Mortality, education, Survival rate, Aged, Demography, Nutrition, Vitamin D deficiency, Biology and life sciences, business.industry, lcsh:R, Rannsóknir, medicine.disease, Metabolic Disorders, People and Places, 570 Life sciences, biology, lcsh:Q, business, Mathematics, Meta analysis, Meta-Analysis
Abstract: Background Vitamin D deficiency may be a risk factor for mortality but previous meta-analyses lacked standardization of laboratory methods for 25-hydroxyvitamin D (25[OH]D) concentrations and used aggregate data instead of individual participant data (IPD). We therefore performed an IPD meta-analysis on the association between standardized serum 25(OH)D and mortality. Methods In a European consortium of eight prospective studies, including seven general population cohorts, we used the Vitamin D Standardization Program (VDSP) protocols to standardize 25(OH)D data. Meta-analyses using a one step procedure on IPD were performed to study associations of 25(OH)D with all-cause mortality as the primary outcome, and with cardiovascular and cancer mortality as secondary outcomes. This meta-analysis is registered at ClinicalTrials.gov, number NCT02438488. Findings We analysed 26916 study participants (median age 61.6 years, 58% females) with a median 25(OH)D concentration of 53.8 nmol/L. During a median follow-up time of 10.5 years, 6802 persons died. Compared to participants with 25(OH)D concentrations of 75 to 99.99 nmol/L, the adjusted hazard ratios (with 95% confidence interval) for mortality in the 25(OH)D groups with 40 to 49.99, 30 to 39.99, and, This project has received funding from the European Community’s Seventh Framework Programme (FP7/2007-2013) under Grant Agreement 613977 for the ODIN Integrated Project [Food-based solutions for optimal vitamin D nutrition and health through the life cycle http://www.odin-vitd.eu/]. Funding for the individual studies contributing data to this effort can be found in Appendix (S1 File), section 11.
Published: 2017

42. Interstitial lung abnormalities in the AGES-Reykjavik study

Author: Vilmundur Gudnason, Gunnar Gudmundsson, David A. Schwartz, Hiroto Hatabu, Lenore J. Launer, Tetsuro Araki, Rachel K. Putman, Mishuki Nishino, Tamara B. Harris, Sigurdur Sigurdsson, Gary M. Hunninghake, Ivan O. Rosas, Elias F. Gudmundsson, Thor Aspelund, and Gudny Eiriksdottir
Subjects: medicine.medical_specialty, Pathology, Lung, business.industry, Hazard ratio, Promoter polymorphism, Odds ratio, Confidence interval, Minor allele frequency, medicine.anatomical_structure, Increased risk, Internal medicine, Cohort, medicine, business
Abstract: Background: Interstitial lung abnormalities (ILA) have been associated with physiologic and genetic abnormalities but these associations, and the association between ILA and mortality, have not been previously evaluated in older adults. Objectives: To explore the associations between important predictors and outcomes of ILA in a cohort of older adults from the Age/Gene Environment Susceptibility (AGES) Reykjavik Study. Methods: ILA were visually assessed in chest CT scans from 5,320 AGES-Reykjavik participants. Results: ILA were present in 378 (7%), 1726 (32%) had indeterminate ILA status and 3216 (61%) had no ILA. Compared to those without ILA, those with ILA were more likely to be older and male, and had increased tobacco smoke exposure. After adjustment for covariates, ILA were also associated with an increased risk of all-cause mortality (Hazard Ratio 1.3, 95% CI 1.2-1.4, P MUC5B promoter polymorphism (odds ratio [OR] 2.7, 95% Confidence Interval [CI] 2.2, 3.2, P MUC5B promoter polymorphism was independently associated with all subtypes of ILA with the exception of those characterized by centrilobular nodules alone. Conclusions: Comparable to previous studies, those with ILA in the AGES-Reykjavik, were more likely to be older, to have increased tobacco exposure, and to have increasing copies of the minor allele of the MUC5B promoter polymorphism. Older adults with ILA in the AGES-Reykjavik had an increased rate of mortality.
Published: 2016

43. Obstructive sleep apnea and cancer- A nationwide epidemiological survey

Author: Elias F. Gudmundsson and Thorarinn Gislason
Subjects: medicine.medical_specialty, business.industry, Incidence (epidemiology), Cancer, medicine.disease, Surgery, Obstructive sleep apnea, Prostate cancer, Breast cancer, Standardized mortality ratio, Internal medicine, Epidemiology, medicine, business, Body mass index
Abstract: Background. Several epidemiological studies have reported an increased cancer incidence among subjects with obstructive sleep apnea (OSA) and in animal models intermittent hypoxia has been related to markers of cancer activity. Aims. To report nationwide data on the prevalence and incidence of cancer among all diagnosed Icelandic OSA patients (total population 320,000) Methods. Altogether 8.833 Icelanders 20 years and older (6311 males and 2522 females) had ever been diagnosed with clinically significant OSA from 1987 until December 2014. All subjects ever diagnosed with cancer in this group until 2014, were identified in the Icelandic cancer register. Standardized incidence ratio (SIR) was estimated. Results. The average age at OSA-diagnosis for males and females was 52.8 and 56.2 years, and for incident cancer 68.1 and. 66.6 years, respectively Among the OSA patients altogether 512 had been diagnosed with cancer when they were diagnosed with OSA. In the 88.542 person years of follow-up after OSA diagnosis there were 869 incident cancer cases (10.4) The most common incident cancer in females was breast cancer (n=68, 28%) and prostate cancer in males (n=200, 32%). OSA patients with cancer had similar body mass index, OSA severity and age at OSA diagnosis as those not diagnosed. In the ongoing age and gender specific risk analysis subjects under 65 years of age were at increased cancer risk (SIR: 1.2(1.1;1.3)), especially melanoma that accounted for 3% of incident cases in females and males (8/19 cases, SIR: 2.2(1.2;4.10) and 3.2(1.5;6.7),respectively) Conclusions. Nationwide Icelandic data show that OSA has a moderate risk association with some cancer types among subjects less than 65 years of age.
Published: 2016

44. High serum miRNA 550a-5p levels are risk factors for incident fractures in older postmenopausal women with type 2 diabetes

Author: Thomas M. Link, Tamara B. Harris, Elias F. Gudmundsson, Vilmundur Gudnasson, Ann V. Schwartz, Klemens Vierlinger, Gudny Eiriksdottir, Johannes Grillari, Thor Aspelund, Ursula Heilmeier, Fabian Schroeder, Susanna Skalicky, Iryna Lobach, Sylvia Weilner, and Matthias Hackl
Subjects: Oncology, medicine.medical_specialty, Postmenopausal women, Endocrinology, business.industry, Internal medicine, microRNA, High serum, medicine, General Medicine, Type 2 diabetes, medicine.disease, business
Published: 2016

45. Association Between Interstitial Lung Abnormalities and All-Cause Mortality

Author: Vilmundur Gudnason, Gregory L. Kinney, John E. Hokanson, Wei Gao, Rachel K. Putman, Elias F. Gudmundsson, Mizuki Nishino, Raúl San José Estépar, Edwin K. Silverman, Gary M. Hunninghake, Tamara B. Harrris, Hiroto Hatabu, Alejandro A. Diaz, Udo Hoffmann, Michelle C. Williams, Lenore J. Launer, Harvey O. Coxson, Oscar E. Zazueta, Josée Dupuis, Ivan O. Rosas, Yuka Okajima, Gudny Eiriksdottir, Souheil El-Chemaly, Thor Aspelund, Gunnar Gudmundsson, Sigurdur Sigurdsson, Matthew J. Budoff, Tetsuro Araki, George R. Washko, William MacNee, Jeanne C. Latourelle, Bartolome R. Celli, Isis E. Fernandez, Michael H. Cho, Rola Harmouche, John T. Murchison, George T. O'Connor, James C. Ross, and Christopher J. O'Donnell
Subjects: Male, medicine.medical_specialty, Population, Coronary Artery Disease, Gastroenterology, Article, Cohort Studies, 03 medical and health sciences, Idiopathic pulmonary fibrosis, Pulmonary Disease, Chronic Obstructive, 0302 clinical medicine, Framingham Heart Study, Internal medicine, Cause of Death, Neoplasms, Pulmonary fibrosis, medicine, Prevalence, Humans, Lung volumes, 030212 general & internal medicine, Prospective Studies, education, Prospective cohort study, Proportional Hazards Models, COPD, education.field_of_study, business.industry, Smoking, General Medicine, medicine.disease, Surgery, Radiography, 030228 respiratory system, Pulmonary Emphysema, Cohort, Female, business
Abstract: IMPORTANCE Interstitial lung abnormalities have been associated with lower 6-minute walk distance, diffusion capacity for carbon monoxide, and total lung capacity. However, to our knowledge, an association with mortality has not been previously investigated. OBJECTIVE To investigate whether interstitial lung abnormalities are associated with increased mortality. DESIGN, SETTING, AND POPULATION Prospective cohort studies of 2633 participants from the FHS (Framingham Heart Study;computed tomographic [CT] scans obtained September 2008-March 2011), 5320 from the AGES-Reykjavik Study (Age Gene/Environment Susceptibility;recruited January 2002-February 2006), 2068 from the COPDGene Study (Chronic Obstructive Pulmonary Disease;recruited November 2007-April 2010), and 1670 from ECLIPSE (Evaluation of COPD Longitudinally to Identify Predictive Surrogate Endpoints;between December 2005 -December 2006). EXPOSURES Interstitial lung abnormality status as determined by chest CT evaluation. MAIN OUTCOMES AND MEASURES All-cause mortality over an approximate 3- to 9-year median follow-up time. Cause-of-death information was also examined in the AGES-Reykjavik cohort. RESULTS Interstitial lung abnormalities were present in 177 (7%) of the 2633 participants from FHS, 378 (7%) of 5320 from AGES-Reykjavik, 156 (8%) of 2068 from COPDGene, and in 157 (9%) of 1670 from ECLIPSE. Over median follow-up times of approximately 3 to 9 years, there were more deaths (and a greater absolute rate of mortality) among participants with interstitial lung abnormalities when compared with those who did not have interstitial lung abnormalities in the following cohorts: 7% vs 1% in FHS (6% difference [95% CI, 2% to 10%]), 56% vs 33% in AGES-Reykjavik (23% difference [95% CI, 18% to 28%]), and 11% vs 5% in ECLIPSE (6% difference [95% CI, 1% to 11%]). After adjustment for covariates, interstitial lung abnormalities were associated with a higher risk of death in the FHS (hazard ratio [HR], 2.7 [95% CI, 1]to 6.5];P = .03), AGES-Reykjavik (HR, 1.3 [95% CI, 1.2 to 1.4];P < .001), COPDGene (HR, 1.8 [95% CI, 1.1to 2.8];P = .01), and ECLIPSE (HR, 1.4 [95% CI, 1]to 2.0];P = .02) cohorts. In the AGES-Reykjavik cohort, the higher rate of mortality could be explained by a higher rate of death due to respiratory disease, specifically pulmonary fibrosis. CONCLUSIONS AND RELEVANCE In 4 separate research cohorts, interstitial lung abnormalities were associated with a greater risk of all-cause mortality. The clinical implications of this association require further investigation.
Published: 2016

46. Coronary artery calcium distributions in older persons in the AGES-Reykjavik study

Author: Sigurdur Sigurdsson, Thor Aspelund, Vilmundur Gudnason, Elias F. Gudmundsson, Lenore J. Launer, and Tamara B. Harris
Subjects: Male, medicine.medical_specialty, Epidemiology, Cross-sectional study, Iceland, Negative binomial distribution, Coronary Artery Disease, Risk Assessment, Article, Coronary artery disease, Age Distribution, Sex Factors, Risk Factors, Internal medicine, Linear regression, Prevalence, medicine, Humans, cardiovascular diseases, Risk factor, Aged, Aged, 80 and over, business.industry, Calcinosis, nutritional and metabolic diseases, Regression analysis, Middle Aged, Atherosclerosis, medicine.disease, Surgery, Quantile regression, Cross-Sectional Studies, cardiovascular system, Cardiology, population characteristics, Regression Analysis, Female, Tomography, X-Ray Computed, business, Risk assessment
Abstract: Coronary Artery Calcium (CAC) is a sign of advanced atherosclerosis and an independent risk factor for cardiac events. Here, we describe CAC-distributions in an unselected aged population and compare modelling methods to characterize CAC-distribution. CAC is difficult to model because it has a skewed and zero inflated distribution with over-dispersion. Data are from the AGES-Reykjavik sample, a large population based study [2002-2006] in Iceland of 5,764 persons aged 66-96 years. Linear regressions using logarithmic- and Box-Cox transformations on CAC+1, quantile regression and a Zero-Inflated Negative Binomial model (ZINB) were applied. Methods were compared visually and with the PRESS-statistic, R(2) and number of detected associations with concurrently measured variables. There were pronounced differences in CAC according to sex, age, history of coronary events and presence of plaque in the carotid artery. Associations with conventional coronary artery disease (CAD) risk factors varied between the sexes. The ZINB model provided the best results with respect to the PRESS-statistic, R(2), and predicted proportion of zero scores. The ZINB model detected similar numbers of associations as the linear regression on ln(CAC+1) and usually with the same risk factors.
Published: 2012

47. Carotid Plaque is a Strong Surrogate Marker for CAC and Subclinical CHD in the General Population

Author: Vilmundur Gudnason, Sigurdur Sigurdsson, Elias F. Gudmundsson, Gudlaug Bjornsdottir, Gudny Eiriksdottir, Bolli Thorsson, and Thor Aspelund
Subjects: medicine.medical_specialty, education.field_of_study, business.industry, Surrogate endpoint, Population, 030209 endocrinology & metabolism, General Medicine, 030204 cardiovascular system & hematology, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, Internal Medicine, Cardiology, Medicine, Cardiology and Cardiovascular Medicine, business, education, Subclinical infection
Published: 2018

48. Cavi an Independent Predictor of CHD

Author: Bolli Thorsson, Elias F. Gudmundsson, Vilmundur Gudnason, Orn Olafsson, and Thor Aspelund
Subjects: medicine.medical_specialty, business.industry, Internal medicine, Internal Medicine, medicine, Cardiology, General Medicine, Cardiology and Cardiovascular Medicine, business, Independent predictor
Published: 2018

49. Prevalence and complications of chronic kidney disease in a representative elderly population in Iceland

Author: Hocine Tighiouart, Elias F. Gudmundsson, Hrefna Gudmundsdottir, Lesley A. Inker, Olafur S. Indridason, Andrew S. Levey, Gudny Eiriksdottir, Aghogho Okparavero, Vilmundur Gudnason, and Meredith C. Foster
Subjects: Male, medicine.medical_specialty, Population, 030232 urology & nephrology, Iceland, Renal function, Cutting-Edge Renal Science, urologic and male genital diseases, Gastroenterology, 03 medical and health sciences, Hyperphosphatemia, 0302 clinical medicine, Metabolic Diseases, Interquartile range, Risk Factors, Internal medicine, medicine, Prevalence, Humans, 030212 general & internal medicine, Hypoalbuminemia, Renal Insufficiency, Chronic, education, Aged, 80 and over, Transplantation, education.field_of_study, biology, business.industry, Age Factors, Anemia, medicine.disease, female genital diseases and pregnancy complications, Endocrinology, Cross-Sectional Studies, Cystatin C, Nephrology, Cardiovascular Diseases, Albuminuria, biology.protein, Female, medicine.symptom, business, Kidney disease, Glomerular Filtration Rate
Abstract: BACKGROUND Chronic kidney disease (CKD) is common in the elderly, but data are limited on the distribution of glomerular filtration rate (GFR) and albuminuria and the prevalence of CKD and related complications in this population. METHODS A cross-sectional study of 3173 older Icelandic adults [42% men; mean (standard deviation, SD) age of 80 (5) years] was performed to examine the distribution of estimated glomerular filtration rate (eGFR) from creatinine and cystatin C, the albumin-to-creatinine ratio (ACR), and CKD-related metabolic complications (hyperparathyroidism, anemia, hypoalbuminemia, increased anion gap, acidosis, hyperphosphatemia and hyperkalemia). RESULTS There was substantial variability in eGFR [mean (SD) 64 (18) mL/min/1.73 m(2)] and ACR [median (interquartile range) 8 (5, 17) mg/g]. The prevalence (95% confidence interval) of reduced eGFR ( 30 mg/g) and CKD (either reduced eGFR or albuminuria) was 40% (38-41), 14% (12-15) and 45% (43-47), respectively. The prevalence of complications was higher among those with versus without CKD: hyperparathyroidism (38 versus 15%), anemia (26 versus 14%), hypoalbuminemia (19 versus 13%), increased anion gap (9 versus 5%), acidosis (5 versus 1%); (P ≤ 0.02 for all), except hyperphosphatemia (1 versus 1%) and hyperkalemia (0% overall). CONCLUSIONS The burden of CKD and CKD-related complications is high among community dwelling elderly Icelandic adults. The wide range of eGFR and ACR suggests heterogeneity in processes leading to CKD and that factors beyond aging contribute to the development of CKD in the elderly.
Published: 2015

50. The MUC5B promoter polymorphism is associated with specific interstitial lung abnormality subtypes

Author: Masahiro Yanagawa, Gudny Eiriksdottir, David A. Schwartz, Mizuki Nishino, Gary M. Hunninghake, Tetsuro Araki, Gunnar Gudmundsson, Michael H. Cho, Hiroto Hatabu, Noriyuki Tomiyama, Benjamin A. Raby, Yoshitake Yamada, Souheil El-Chemaly, Rachel K. Putman, James C. Ross, Tamara B. Harris, Edwin K. Silverman, Sigurdur Sigurdsson, Thor Aspelund, George R. Washko, Lenore J. Launer, Ivan O. Rosas, Ezra R. Miller, Elias F. Gudmundsson, Vilmundur Gudnason, and Raúl San José Estépar
Subjects: Male, Pulmonary and Respiratory Medicine, Pathology, medicine.medical_specialty, Genotype, Population, Iceland, Promoter polymorphism, Gastroenterology, Article, 03 medical and health sciences, 0302 clinical medicine, Usual interstitial pneumonia, Polymorphism (computer science), Internal medicine, medicine, Humans, Longitudinal Studies, 030212 general & internal medicine, Promoter Regions, Genetic, education, Genotyping, Aged, Aged, 80 and over, education.field_of_study, Polymorphism, Genetic, Lung, business.industry, medicine.disease, Mucin-5B, Logistic Models, medicine.anatomical_structure, ROC Curve, 030228 respiratory system, Female, Abnormality, Lung Diseases, Interstitial, Tomography, X-Ray Computed, business
Abstract: The MUC5B promoter polymorphism (rs35705950) has been associated with interstitial lung abnormalities (ILA) in white participants from the general population; whether these findings are replicated and influenced by the ILA subtype is not known. We evaluated the associations between the MUC5B genotype and ILA in cohorts with extensive imaging characterisation.We performed ILA phenotyping and MUC5B promoter genotyping in 5308 and 9292 participants from the AGES-Reykjavik and COPDGene cohorts, respectively.We found that ILA was present in 7% of participants from the AGES-Reykjavik, 8% of non-Hispanic white participants from COPDGene and 7% of African-American participants from COPDGene. Although the MUC5B genotype was strongly associated (after correction for multiple testing) with ILA (OR 2.1, 95% CI 1.8-2.4, p=1×10-26), there was evidence of significant heterogeneity between cohorts (I2=81%). When narrowed to specific radiologic subtypes, (e.g. subpleural ILA), the MUC5B genotype remained strongly associated (OR 2.6, 95% CI 2.2-3.1, p=1×10-30) with minimal heterogeneity (I2=0%). Although there was no evidence that the MUC5B genotype influenced survival, there was evidence that MUC5B genotype improved risk prediction for possible usual interstitial pneumonia (UIP) or a UIP pattern in non-Hispanic white populations.The MUC5B promoter polymorphism is strongly associated with ILA and specific radiologic subtypes of ILA, with varying degrees of heterogeneity in the underlying populations.
Published: 2017

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