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1. Panel stacking is a threat to consensus statement validity

Author

Kepp, K. P., Aavitsland, P., Ballin, M., Balloux, F., Baral, S., Bardosh, K., Bauchner, H., Bendavid, E., Bhopal, R., Blumstein, D. T., Boffetta, P., Bourgeois, F., Brufsky, A., Collignon, P. J., Cripps, S., Cristea, I. A., Curtis, N., Djulbegovic, B., Faude, O., Flacco, M. E., Guyatt, G. H., Hajishengallis, G., Hemkens, L. G., Hoffmann, T., Joffe, A. R., Klassen, T. P., Koletsi, D., Kontoyiannis, D. P., Kuhl, E., La Vecchia, C., Lallukka, T., Lambris, J., Levitt, M., Makridakis, S., Maltezou, H. C., Manzoli, L., Marusic, A., Mavragani, C., Moher, D., Mol, B. W., Muka, T., Naudet, F., Noble, P. W., Nordström, Anna, Nordström, P., Pandis, N., Papatheodorou, S., Patel, C. J., Petersen, I., Pilz, S., Plesnila, N., Ponsonby, A. -L, Rivas, M. A., Saltelli, A., Schabus, M., Schippers, M. C., Schünemann, H., Solmi, M., Stang, A., Streeck, H., Sturmberg, J. P., Thabane, L., Thombs, B. D., Tsakris, A., Wood, S. N., Ioannidis, J. P. A., Kepp, K. P., Aavitsland, P., Ballin, M., Balloux, F., Baral, S., Bardosh, K., Bauchner, H., Bendavid, E., Bhopal, R., Blumstein, D. T., Boffetta, P., Bourgeois, F., Brufsky, A., Collignon, P. J., Cripps, S., Cristea, I. A., Curtis, N., Djulbegovic, B., Faude, O., Flacco, M. E., Guyatt, G. H., Hajishengallis, G., Hemkens, L. G., Hoffmann, T., Joffe, A. R., Klassen, T. P., Koletsi, D., Kontoyiannis, D. P., Kuhl, E., La Vecchia, C., Lallukka, T., Lambris, J., Levitt, M., Makridakis, S., Maltezou, H. C., Manzoli, L., Marusic, A., Mavragani, C., Moher, D., Mol, B. W., Muka, T., Naudet, F., Noble, P. W., Nordström, Anna, Nordström, P., Pandis, N., Papatheodorou, S., Patel, C. J., Petersen, I., Pilz, S., Plesnila, N., Ponsonby, A. -L, Rivas, M. A., Saltelli, A., Schabus, M., Schippers, M. C., Schünemann, H., Solmi, M., Stang, A., Streeck, H., Sturmberg, J. P., Thabane, L., Thombs, B. D., Tsakris, A., Wood, S. N., and Ioannidis, J. P. A.

Abstract

Consensus statements can be very influential in medicine and public health. Some of these statements use systematic evidence synthesis but others fail on this front. Many consensus statements use panels of experts to deduce perceived consensus through Delphi processes. We argue that stacking of panel members toward one particular position or narrative is a major threat, especially in absence of systematic evidence review. Stacking may involve financial conflicts of interest, but nonfinancial conflicts of strong advocacy can also cause major bias. Given their emerging importance, we describe here how such consensus statements may be misleading, by analyzing in depth a recent high-impact Delphi consensus statement on COVID-19 recommendations as a case example. We demonstrate that many of the selected panel members and at least 35% of the core panel members had advocated toward COVID-19 elimination (Zero-COVID) during the pandemic and were leading members of aggressive advocacy groups. These advocacy conflicts were not declared in the Delphi consensus publication, with rare exceptions. Therefore, we propose that consensus statements should always require rigorous evidence synthesis and maximal transparency on potential biases toward advocacy or lobbyist groups to be valid. While advocacy can have many important functions, its biased impact on consensus panels should be carefully avoided.

Published
2024
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6. Does reproductive stage impact cardiovascular disease risk factors? Results from a population-based cohort in Lausanne (CoLaus study)

Author

Raguindin, P.F. Cardona, I. Muka, T. Lambrinoudaki, I. Gebhard, C. Franco, O.H. Marques-Vidal, P. Glisic, M.

Abstract

Context: Menopause has been associated with adverse cardiovascular disease (CVD) risk profile, yet it is unclear whether the changes in CVD risk factors differ by reproductive stage independently of underlying ageing trajectories. Design: The CoLaus study is a prospective population-based cohort study in Lausanne, Switzerland. Patients: We used data from women at baseline and follow-up (mean: 5.6 ± 0.5 years) from 2003 to 2012 who did not use hormone therapy. We classified women into (i) premenopausal, (ii) menopausal transition, (iii) early (≤5 years) and (iv) late (>5 years) postmenopausal by comparing their menstruation status at baseline and follow-up. Measurements: We measured fasting lipids, glucose and cardiovascular inflammatory markers. We used repeated measures (linear mixed models) for longitudinal analysis, using premenopausal women as a reference category. We adjusted analyses for age, medications and lifestyle factors. Results: We used the data from 1710 women aged 35–75 years. Longitudinal analysis showed that the changes in CVD risk factors were not different in the other three menopausal categories compared to premenopausal women. When age was used as a predictor variable and adjusted for menopause status, most CVD risk factors increased, while interleukin-6 and interleukin-1β decreased with advancing age. Conclusion: The current study suggests that women have a worsening cardiovascular risk profile as they age, and although menopausal women may have higher levels of cardiovascular risk factors compared to premenopausal women at any given time, the 5-year changes in cardiovascular risk factors may not depend on the reproductive stage. © 2022 The Authors. Clinical Endocrinology published by John Wiley & Sons Ltd.

Published
2022

9. Phytochemical characterization of turnip greens (Brassica rapa ssp. rapa): A systematic review

Author

Dejanovic, G.M. (Gordana M.), Asllanaj, E. (Eralda), Gamba, M. (Magda), Raguindin, P. (PeterFrancis), Itodo, O.A. (Oche Adam), Minder, B. (Beatrice), Bussler, W. (Weston), Metzger, B. (Brandon), Muka, T. (Taulant), Glisic, M. (Marija), Kern, H. (Hua), Dejanovic, G.M. (Gordana M.), Asllanaj, E. (Eralda), Gamba, M. (Magda), Raguindin, P. (PeterFrancis), Itodo, O.A. (Oche Adam), Minder, B. (Beatrice), Bussler, W. (Weston), Metzger, B. (Brandon), Muka, T. (Taulant), Glisic, M. (Marija), and Kern, H. (Hua)

Abstract

Objective The Turnip (Brassica rapa L. ssp. rapa) is a leaf and root vegetable grown and consumed worldwide. The consumption of Turnip has been associated with beneficial effects on human health due to their phytochemicals that may control a variety of physiological functions, including antioxidant activity, enzyme regulation, and apoptotic control and the cell cycle. The current systematic review of the literature aims to evaluate both the profile and quantity of phytochemicals commonly found in Turnip greens and to provide perspectives for further investigation. Methods This review was conducted following the PRISMA guidelines. Four bibliographic databases (PubMed, Embase, Web-of-Science and Cochrane Central Register of Controlled Trials) were searched to identify published studies until April 8th, 2020 (date last searched) without data and language restriction. Studies were included if they used samples of Turnip greens (the leaves), and evaluated its phytochemical content. Two reviewers independently evaluated the titles and abstracts according to the selection criteria. For each potentially eligible study, two reviewers assessed the full-texts and independently extracted the data using a predesigned data extraction form. Results Based on the search strategy 5,077 potentially relevant citations were identified and full texts of 37 studies were evaluated, among which 18 studies were eligible to be included in the current review. The majority of included studies were focused on identification of glucosinolates and isothiocyanates (n = 14, 82%), four studies focused on organic acids, and five studies reported phenolic component profile in Turnip greens. Among included studies nine studies (50%) provided information on phytochemic

Published
2021
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10. Phytochemical characterization of turnip greens (Brassica rapa ssp. rapa): A systematic review

Author

Dejanovic, GM, Asllanaj, Eralda, Gamba, M, Raguindin, P, Itodo, OA, Minder, B, Bussler, W, Metzger, B, Muka, T, Glisic, Marija, Kern, H, Dejanovic, GM, Asllanaj, Eralda, Gamba, M, Raguindin, P, Itodo, OA, Minder, B, Bussler, W, Metzger, B, Muka, T, Glisic, Marija, and Kern, H

Abstract

Objective The Turnip (Brassica rapa L. ssp. rapa) is a leaf and root vegetable grown and consumed worldwide. The consumption of Turnip has been associated with beneficial effects on human health due to their phytochemicals that may control a variety of physiological functions, including antioxidant activity, enzyme regulation, and apoptotic control and the cell cycle. The current systematic review of the literature aims to evaluate both the profile and quantity of phytochemicals commonly found in Turnip greens and to provide perspectives for further investigation. Methods This review was conducted following the PRISMA guidelines. Four bibliographic databases (PubMed, Embase, Web-of-Science and Cochrane Central Register of Controlled Trials) were searched to identify published studies until April 8th, 2020 (date last searched) without data and language restriction. Studies were included if they used samples of Turnip greens (the leaves), and evaluated its phytochemical content. Two reviewers independently evaluated the titles and abstracts according to the selection criteria. For each potentially eligible study, two reviewers assessed the full-texts and independently extracted the data using a predesigned data extraction form. Results Based on the search strategy 5,077 potentially relevant citations were identified and full texts of 37 studies were evaluated, among which 18 studies were eligible to be included in the current review. The majority of included studies were focused on identification of glucosinolates and isothiocyanates (n = 14, 82%), four studies focused on organic acids, and five studies reported phenolic component profile in Turnip greens. Among included studies nine studies (50%) provided information on phytochemical’s content. We found 129 phytochemicals (19 glucosinolates, 33 glucosinolate-breakdown products, 10 organic acids and 59 polyphenolic compounds) reported in Turnip greens. Flavonoids were mainly present as quercetin, kaempferol and iso

Published
2021

11. Genomic analysis of diet composition finds novel loci and associations with health and lifestyle

Author

Meddens, S.F.W. (Fleur), Vlaming, R. (Ronald) de, Bowers, P. (Peter), Burik, C.A.P. (Casper A. P.), Linnér, R.K. (Richard Karlsson), Lee, C. (Chanwook), Okbay, A. (Aysu), Turley, P. (Patrick), Rietveld, C.A. (Cornelius A.), Fontana, M.A. (Mark Alan), Ghanbari, M. (Mohsen), Imamura, F. (Fumiaki), McMahon, G. (George), Most, P.J. (Peter) van der, Voortman, R.G. (Trudy), Wade, K.H. (Kaitlin H.), Anderson, E.L. (Emma L.), Braun, K.V.E. (Kim), Emmett, P.M. (Pauline M.), Esko, T. (Tõnu), Gonzalez, J.R. (Juan), Kiefte-de Jong, J.C. (Jessica), Langenberg, C. (Claudia), Luan, J. (Jian’an), Muka, T. (Taulant), Ring, S.M. (Susan), Rivadeneira, F. (Fernando), Snieder, H. (Harold), Rooij, F.J.A. (Frank) van, Wolffenbuttel, B.H.R. (Bruce), Smith, G.D. (George Davey), Franco, O.H. (Oscar H.), Forouhi, N.G. (Nita), Ikram, M.A. (Arfan), Uitterlinden, A.G. (André), van Vliet-Ostaptchouk, J.V. (Jana V.), Wareham, N.J. (Nick), Cesarini, D. (David), Harden, K.P. (K. Paige), Lee, J.J. (James J.), Benjamin, D.J. (Daniel J.), Chow, C.C. (Carson C.), Koellinger, P.D. (Philipp D.), Meddens, S.F.W. (Fleur), Vlaming, R. (Ronald) de, Bowers, P. (Peter), Burik, C.A.P. (Casper A. P.), Linnér, R.K. (Richard Karlsson), Lee, C. (Chanwook), Okbay, A. (Aysu), Turley, P. (Patrick), Rietveld, C.A. (Cornelius A.), Fontana, M.A. (Mark Alan), Ghanbari, M. (Mohsen), Imamura, F. (Fumiaki), McMahon, G. (George), Most, P.J. (Peter) van der, Voortman, R.G. (Trudy), Wade, K.H. (Kaitlin H.), Anderson, E.L. (Emma L.), Braun, K.V.E. (Kim), Emmett, P.M. (Pauline M.), Esko, T. (Tõnu), Gonzalez, J.R. (Juan), Kiefte-de Jong, J.C. (Jessica), Langenberg, C. (Claudia), Luan, J. (Jian’an), Muka, T. (Taulant), Ring, S.M. (Susan), Rivadeneira, F. (Fernando), Snieder, H. (Harold), Rooij, F.J.A. (Frank) van, Wolffenbuttel, B.H.R. (Bruce), Smith, G.D. (George Davey), Franco, O.H. (Oscar H.), Forouhi, N.G. (Nita), Ikram, M.A. (Arfan), Uitterlinden, A.G. (André), van Vliet-Ostaptchouk, J.V. (Jana V.), Wareham, N.J. (Nick), Cesarini, D. (David), Harden, K.P. (K. Paige), Lee, J.J. (James J.), Benjamin, D.J. (Daniel J.), Chow, C.C. (Carson C.), and Koellinger, P.D. (Philipp D.)

Abstract

We conducted genome-wide association studies (GWAS) of relative intake from the macronutrients fat, protein, carbohydrates, and sugar in over 235,000 individuals of European ancestries. We identified 21 unique, approximately independent lead SNPs. Fourteen lead SNPs are uniquely associated with one macronutrient at genome-wide significance (P < 5 × 10−8), while five of the 21 lead SNPs reach suggestive significance (P < 1 × 10−5) for at least one other macronutrient. While the phenotypes are genetically correlated, each phenotype carries a partially unique genetic architecture. Relative protein intake exhibits the strongest relationships with poor health, including positive genetic associations with obesity, type 2 diabetes, and heart disease (rg ≈ 0.15–0.5). In contrast, relative carbohydrate and sugar intake have negative genetic correlations with waist circumference, waist-hip ratio, and neighborhood deprivation (|rg| ≈ 0.1–0.3) and positive genetic correlations with physical activity (rg ≈ 0.1 and 0.2). Relative fat intake has no consistent pattern of genetic correlations with poor health but has a negative genetic correlation with educational attainment (rg ≈−0.1). Although our analyses do not allow us to draw causal conclusions, we find no evidence of negative health consequences associated with relative carbohydrate, sugar, or fat intake. However, our results are consistent with the hypothesis that relative protein intake plays a role in the etiology of metabolic dysfunction.

Published
2020
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12. Fetal sex and maternal pregnancy outcomes: a systematic review and meta-analysis

Author

Broere-Brown, Z.A. (Zoe), Adank, M.A. (Muriel), Benschop, H.A.M. (Laura), Tielemans, M.J. (Myrte), Muka, T. (Taulant), Gonçalves, R. (Romy), Bramer, W.M. (Wichor), Schoufour, J.D. (Josje), Voortman, R.G. (Trudy), Steegers, E.A.P. (Eric), Franco, O.H. (Oscar H.), Schalekamp-Timmermans, S. (Sarah), Broere-Brown, Z.A. (Zoe), Adank, M.A. (Muriel), Benschop, H.A.M. (Laura), Tielemans, M.J. (Myrte), Muka, T. (Taulant), Gonçalves, R. (Romy), Bramer, W.M. (Wichor), Schoufour, J.D. (Josje), Voortman, R.G. (Trudy), Steegers, E.A.P. (Eric), Franco, O.H. (Oscar H.), and Schalekamp-Timmermans, S. (Sarah)

Abstract

BACKGROUND: Since the placenta also has a sex, fetal sex-specific differences in the occurrence of placenta-mediated complications could exist. OBJECTIVE: To determine the association of fetal sex with multiple maternal pregnancy complications. SEARCH STRATEGY: Six electronic databases Ovid MEDLINE, EMBASE, Cochrane Central, Web-of-Science, PubMed, and Google Scholar were systematically searched to identify eligible studies. Reference lists of the included studies and contact with experts were also used for identification of studies. SELECTION CRITERIA: Observational studies that assessed fetal sex and the presence of maternal pregnancy complications within singleton pregnancies. DATA COLLECTION AND ANALYSES: Data were extracted by 2 independent reviewers using a predesigned data collection form. MAIN RESULTS: From 6522 original references, 74 studies were selected, including over 12,5 million women. Male fetal sex was associated with term pre-eclampsia (pooled OR 1.07 [95%CI 1.06 to 1.09]) and gestational diabetes (pooled OR 1.04 [1.02 to 1.07]). All other pregnancy complications (i.e., gestational hypertension, total pre-eclampsia, eclampsia, placental abruption, and post-partum hemorrhage) tended to be associated with male fetal sex, except for preterm pre-eclampsia, which was more associated with female fetal sex. Overall quality of the included studies was good. Between-study heterogeneity was high due to differences in study population and outcome definition. CONCLUSION: This meta-analysis suggests that the occurrence of pregnancy complications differ according to fetal sex with a higher cardiovascular and

Published
2020
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13. Prevalence of overweight and metabolic syndrome, and associated sociodemographic factors among adult Ecuadorian populations: the ENSANUT-ECU study

Author

Pérez-Galarza, J. (J.), Baldeón, L. (L.), Franco, O.H. (O. H.), Muka, T. (Taulant), Drexhage, H.A. (Hemmo), Voortman, R.G. (Trudy), Freire, W.B. (W. B.), Pérez-Galarza, J. (J.), Baldeón, L. (L.), Franco, O.H. (O. H.), Muka, T. (Taulant), Drexhage, H.A. (Hemmo), Voortman, R.G. (Trudy), and Freire, W.B. (W. B.)

Abstract

Background: Obesity and metabolic syndrome (MetS) are key risk factors for type 2 diabetes and cardiovascular disease. Little information exists on the prevalence of obesity and MetS in Latin America and specifically in Ecuador. We aimed to estimate the prevalence of overweight, obesity, and MetS among adults in Ecuador. Methods: We analyzed data from a nation-wide population-based survey in Ecuador (ENSANUT-ECU) among 10,318 participants (3684 men, 6634 women; age range: 18–59 years) conducted in 2012. Data related to residential location (urban versus rural), altitude (< 500, 500–1500 or > 1500 m above sea level (MASL)), region (highland, coast, amazon, or Galápagos), and socioeconomic status were collected. BMI, waist circumference, blood lipids, glucose, and blood pressure were measured by trained fieldworkers following standardized procedures. Results: The age-standardized prevalence of overweight was 39.5%; 22.3% was obese; and 31.2% had MetS. The prevalence of obesity, low HDL-cholesterol, and abdominal obesity were higher in women than in men, whereas men had a higher prevalence of hypertension (p < 0.05). Sex differences were not observed regarding the prevalence of combined MetS. Prevalence of both obesity and MetS was higher in urban areas, at low altitude regions (coast and Galapagos), and at high socioeconomic status (all p < 0.05). Conclusions: Prevalence of obesity and MetS in Ecuador are high. There are important demographic differences in the prevalence of MetS between Ecuadorian subpopulations that requires targeted research and prevention efforts, to hold and reduce the current public health problem of metabolic disorders.

Published
2020
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14. Trajectories of BMI Before Diagnosis of Type 2 Diabetes: The Rotterdam Study

Author

Nano, J. (Jana), Dhana, K. (Klodian), Asllanaj, E. (Eralda), Sijbrands, E. (Eric), Ikram, M.A. (Arfan), Dehghan, A. (Abbas), Muka, T. (Taulant), Franco, O.H. (Oscar H.), Nano, J. (Jana), Dhana, K. (Klodian), Asllanaj, E. (Eralda), Sijbrands, E. (Eric), Ikram, M.A. (Arfan), Dehghan, A. (Abbas), Muka, T. (Taulant), and Franco, O.H. (Oscar H.)

Abstract

Objective: People with diabetes show great variability in weight gain and duration of obesity at the time of diagnosis. BMI trajectories and other cardiometabolic risk factors prior to type 2 diabetes were investigated. Methods: A total of 6,223 participants from the Rotterdam Study cohort were included. BMI patterns before diagnosis of diabetes were identified through latent class trajectories. Results: During a mean follow-up of 13.7 years, 565 participants developed type 2 diabetes. Three distinct trajectories of BMI were identified, including the “progressive overweight” group (n = 481, 85.1%), “progressive weight loss” group (n = 59, 10.4%), and “persistently high BMI” group (n = 25, 4.4%). The majority, the progressive overweight group, was characterized by a steady increase of BMI in the overweight range 10 years before diabetes diagnosis. The progressive weight loss group had fluctuations of glucose and marked beta cell function loss. The persistently high BMI group was characterized by a slight increase in insulin levels and sharp increase of insulin resistance accompanied by a rapid decrease of beta cell function. Conclusions : Heterogeneity of BMI changes prior to type 2 diabetes was found in a middle-aged and elderly white population. Prevention strategies should be tailored rather than focusing only on high-risk individuals.

Published
2020
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15. Sexually dimorphic DNA-methylation in cardiometabolic health: A systematic review

Author

Asllanaj, Eralda, Zhang, Xiaofang, Ochoa Rosales, Carolina, Nano, Jana, Bramer, WM (Wichor), Portilla Fernández, Eliana, Braun, Kim, Gonzalez Jaramillo, Valentina, Ahrens, W, Ikram, Arfan, Ghanbari, Mohsen, Voortman, Trudy, Franco Duran, OH, Muka, T, Glisic, Marija, Asllanaj, Eralda, Zhang, Xiaofang, Ochoa Rosales, Carolina, Nano, Jana, Bramer, WM (Wichor), Portilla Fernández, Eliana, Braun, Kim, Gonzalez Jaramillo, Valentina, Ahrens, W, Ikram, Arfan, Ghanbari, Mohsen, Voortman, Trudy, Franco Duran, OH, Muka, T, and Glisic, Marija

Published
2020

16. Muscle mass heavily influences creatinine-based renal function estimation: a 12-year longitudinal general population-based cohort study

Author

Groothof, D, primary, Post, A, additional, Polinder-Bos, H.A, additional, Kieneker, L.M, additional, Flores-Guerrero, J.L, additional, Kootstra-Ros, J.E, additional, De Borst, M.H, additional, Gansevoort, R.T, additional, Spycher, B.D, additional, Erler, N.S, additional, Bano, A, additional, Muka, T, additional, Franco, O.H, additional, and Bakker, S.J.L, additional

Published
2020
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18. Dietary Factors and Modulation of Bacteria Strains of Akkermansia muciniphila and Faecalibacterium prausnitzii: A Systematic Review

Author

Verhoog, S., Taneri, P.E., Roa Díaz, Z.M., Marques-Vidal, P., Troup, J.P., Bally, L., Franco, O.H., Glisic, M., and Muka, T.

Subjects
Diet, Faecalibacterium prausnitzii/drug effects, Gastrointestinal Microbiome, Humans, Verrucomicrobia/drug effects, Akkermansia muciniphila, Faecalibacterium prausnitzii, dietary interventions, microbiome, randomized controlled trials, systematic review
Abstract

Akkermansia muciniphila and Faecalibacterium prausnitzii are highly abundant human gut microbes in healthy individuals, and reduced levels are associated with inflammation and alterations of metabolic processes involved in the development of type 2 diabetes. Dietary factors can influence the abundance of A. muciniphila and F. prausnitzii, but the evidence is not clear. We systematically searched PubMed and Embase to identify clinical trials investigating any dietary intervention in relation to A. muciniphila and F. prausnitzii. Overall, 29 unique trials were included, of which five examined A. muciniphila, 19 examined F. prausnitzii, and six examined both, in a total of 1444 participants. A caloric restriction diet and supplementation with pomegranate extract, resveratrol, polydextrose, yeast fermentate, sodium butyrate, and inulin increased the abundance of A. muciniphila, while a diet low in fermentable oligosaccharides, disaccharides, monosaccharides, and polyols decreased the abundance of A. muciniphila. For F. prausnitzii, the main studied intervention was prebiotics (e.g. fructo-oligosaccharides, inulin type fructans, raffinose); seven studies reported an increase after prebiotic intervention, while two studies reported a decrease, and four studies reported no difference. Current evidence suggests that some dietary factors may influence the abundance of A. muciniphila and F. prausnitzii. However, more research is needed to support these microflora strains as targets of microbiome shifts with dietary intervention and their use as medical nutrition therapy in prevention and management of chronic disease.

Published
2019

19. Socioeconomic position, lifestyle habits and biomarkers of epigenetic aging: a multi-cohort analysis

Author

Fiorito, G., Mccrory, C., Robinson, O., Carmeli, C., Rosales, C. O., Zhang, Y., Colicino, E., Dugue, P. -A., Artaud, F., Mckay, G. J., Jeong, A., Mishra, P. P., Nost, T. H., Krogh, V., Panico, S., Sacerdote, C., Tumino, R., Palli, D., Matullo, G., Guarrera, S., Gandini, M., Bochud, M., Dermitzakis, E., Muka, T., Schwartz, J., Vokonas, P. S., Just, A., Hodge, A. M., Giles, G. G., Southey, M. C., Hurme, M. A., Young, I., Mcknight, A. J., Kunze, S., Waldenberger, M., Peters, A., Schwettmann, L., Lund, E., Baccarelli, A., Milne, R. L., Kenny, R. A., Elbaz, A., Brenner, H., Kee, F., Voortman, T., Probst-Hensch, N., Lehtimaki, T., Elliot, P., Stringhini, S., Vineis, P., Polidoro, S., Alberts, J., Alenius, H., Avendano, M., Baltar, V., Bartley, M., Barros, H., Bellone, M., Berger, E., Blane, D., Candiani, G., Carra, L., Castagne, R., Chadeau-Hyam, M., Cima, S., Clavel-Chapelon, F., Costa, G., Courtin, E., Delpierre, C., D'Errico, A., Dermitzakis, M., Elovainio, M., Elliott, P., Fagherazzi, G., Fraga, S., Gares, V., Gerbouin-Rerolle, P., Giles, G., Goldberg, M., Greco, D., Guessous, I., Haba-Rubio, J., Heinzer, R., Hodge, A., Joost, S., Karimi, M., Kelly-Irving, M., Kahonen, M., Karisola, P., Khenissi, L., Kivimaki, M., Laine, J., Lang, T., Laurent, A., Layte, R., Lepage, B., Lorsch, D., Macguire, F., Machell, G., Mackenbach, J., Marmot, M., de Mestral, C., Miller, C., Milne, R., Muennig, P., Nusselder, W., Petrovic, D., Pilapil, L., Preisig, M., Pulkki-Raback, L., Raitakari, O., Ribeiro, A. I., Ricceri, F., Recalcati, P., Reinhard, E., Valverde, J. R., Saba, S., Santegoets, F., Satolli, R., Simmons, T., Severi, G., Shipley, M. J., Tabak, A., Terhi, V., Tieulent, J., Vaccarella, S., Vigna-Taglianti, F., Vollenweider, P., Vuilleumier, N., Zins, M., Medical Research Council (MRC), Commission of the European Communities, BIOS Consortium, Lifepath consortium, Epidemiology, Dermitzakis, Emmanouil, and Stringhini, Silvia

Subjects
Male, Aging, Geriatrics & Gerontology, Disease, epigenetic clocks, Bioinformatics, 0601 Biochemistry and Cell Biology, DISEASE, Epigenesis, Genetic, Cohort Studies, 0302 clinical medicine, Risk Factors, DNA METHYLATION, media_common, 0303 health sciences, education, Lifepath consortium, VDP::Medisinske Fag: 700::Helsefag: 800::Samfunnsmedisin, sosialmedisin: 801, CARDIOVASCULAR RISK, Aged, Aging/genetics, Aging/psychology, DNA Methylation, Educational Status, Female, Humans, Life Style, Mutation, Social Class, biological aging, socioeconomic position, Longevity, ASSOCIATION, Biological aging, Education, Epigenetic clocks, Socioeconomic position, 3. Good health, WIDE METHYLATION, Aging/genetics/psychology, DNA methylation, Biomarker (medicine), HEALTH, BIOS Consortium, Life Sciences & Biomedicine, Research Paper, Cohort study, VDP::Medisinske Fag: 700::Basale medisinske, odontologiske og veterinærmedisinske fag: 710::Medisinsk genetikk: 714, media_common.quotation_subject, CANCER-RISK, 610 Medicine & health, VDP::Medical disciplines: 700::Basic medical, dental and veterinary science disciplines: 710::Medical genetics: 714, Biology, PERIPHERAL-BLOOD, 03 medical and health sciences, SDG 3 - Good Health and Well-being, Genetic, 360 Social problems & social services, 1112 Oncology and Carcinogenesis, Epigenetics, ddc:613, 030304 developmental biology, Science & Technology, Mechanism (biology), MUTATIONS, dNaM, Socioeconomic Position, Biological Aging, Epigenetic Clocks, Cell Biology, 0606 Physiology, DRIFT, VDP::Medical disciplines: 700::Health sciences: 800::Community medicine, Social medicine: 801, 030217 neurology & neurosurgery, Epigenesis
Abstract

Source at https://doi.org/10.18632/aging.101900. Differences in health status by socioeconomic position (SEP) tend to be more evident at older ages, suggesting the involvement of a biological mechanism responsive to the accumulation of deleterious exposures across the lifespan. DNA methylation (DNAm) has been proposed as a biomarker of biological aging that conserves memory of endogenous and exogenous stress during life. We examined the association of education level, as an indicator of SEP, and lifestyle-related variables with four biomarkers of age-dependent DNAm dysregulation: the total number of stochastic epigenetic mutations (SEMs) and three epigenetic clocks (Horvath, Hannum and Levine), in 18 cohorts spanning 12 countries. The four biological aging biomarkers were associated with education and different sets of risk factors independently, and the magnitude of the effects differed depending on the biomarker and the predictor. On average, the effect of low education on epigenetic aging was comparable with those of other lifestyle-related risk factors (obesity, alcohol intake), with the exception of smoking, which had a significantly stronger effect. Our study shows that low education is an independent predictor of accelerated biological (epigenetic) aging and that epigenetic clocks appear to be good candidates for disentangling the biological pathways underlying social inequalities in healthy aging and longevity.

Published
2019

20. Associations of autozygosity with a broad range of human phenotypes

Author

Clark, D.W. (David W), Okada, Y. (Yukinori), Moore, K.H.S. (Kristjan H S), Mason, D. (Dan), Pirastu, N. (Nicola), Gandin, I. (Ilaria), Mattsson, H. (Hannele), Barnes, C.L.K. (Catriona L K), Lin, K. (Kuang), Zhao, J.H. (Jing Hua), Deelen, P. (Patrick), Rohde, R. (Rebecca), Schurmann, C. (Claudia), Guo, X. (Xiuqing), Giulianini, F. (Franco), Zhang, W. (Weihua), Medina-Gomez, M.C. (Carolina), Karlsson, R. (Robert), Bao, Y. (Yanchun), Bartz, T.M. (Traci M), Baumbach, C. (Clemens), Biino, G. (Ginevra), Bixley, M.J. (Matthew J), Brumat, M. (Marco), Chai, J.-F. (Jin-Fang), Corre, T. (Tanguy), Cousminer, D.L. (Diana), Dekker, A.M. (Annelot M), Eccles, D.A. (David A), Eijk, K.R. (Kristel) van, Fuchsberger, C. (Christian), Gao, H. (He), Germain, M. (Marine), Gordon, S.D. (Scott D.), de Haan, H.G. (Hugoline G), Harris, S.E. (Sarah), Hofer, E. (Edith), Huerta-Chagoya, A. (Alicia), Igartua, C. (Catherine), Jansen, I. (Iris), Jia, Y. (Yucheng), Kacprowski, T. (Tim), Karlsson, T. (Torgny), Kleber, M.E. (Marcus), Li, S.A. (Shengchao Alfred), Li-Gao, R. (Ruifang), Mahajan, A. (Anubha), Matsuda, K. (Koichi), Meidtner, K. (Karina), Meng, W. (Weihua), Montasser, M.E. (May E.), Most, P.J. (Peter) van der, Munz, M. (Matthias), Nutile, T. (Teresa), Palviainen, T. (Teemu), Prasad, G. (Gauri), Prasad, R.B. (Rashmi B), Priyanka, T.D.S. (Tallapragada Divya Sri), Rizzi, F. (Federica), Salvi, E. (Erika), Sapkota, B.R. (Bishwa R), Shriner, D. (Daniel), Skotte, L. (Line), Smart, M.C. (Melissa C), Smith, A.V. (Albert), Spek, A. (Ashley) van der, Spracklen, C.N. (Cassandra N), Strawbridge, R.J. (Rona), Tajuddin, S.M. (Salman M), Trompet, S. (Stella), Turman, C. (Constance), Verweij, N. (Niek), Viberti, C. (Clara), Wang, L. (Lihua), Warren, H. (Helen), Wootton, R.E. (Robyn E), Yanek, L.R. (Lisa), Yao, J. (Jie), Yousri, N.A. (Noha A), Zhao, W. (Wei), Adeyemo, A.A. (Adebowale A), Afaq, S. (Saima), Aguilar-Salinas, C.A. (Carlos Alberto), Akiyama, M. (Masato), Albert, M.L. (Matthew L), Allison, M.A. (Matthew A), Alver, M. (Maris), Aung, T. (Tin), Azizi, J. (Joshan), Bentley, A.R. (Amy), Boeing, H. (Heiner), Boerwinkle, E.A. (Eric), Borja, J.B. (Judith B), Borst, G.J. (Gert) de, Bottinger, E.P. (Erwin), Broer, L. (Linda), Campbell, H. (Harry), Chanock, S.J. (Stephen), Chee, M.-L. (Miao-Li), Chen, G. (Guanjie), Chen, Y.-D.I. (Yii-Der I), Chen, Z. (Zhengming), Chiu, Y.-F. (Yen-Feng), Cocca, M. (Massimiliano), Collins, F.S. (Francis), Concas, M.P. (Maria Pina), Corley, J. (Janie), Cugliari, G. (Giovanni), Dam, R.M. (Rob) van, Damulina, A. (Anna), Daneshpour, M.S. (Maryam S), Day, F.R. (Felix), Delgado, G., Dhana, K. (Klodian), Doney, A.S.F. (Alex), Dörr, M. (Marcus), Doumatey, A. (Ayo), Dzimiri, N. (Nduna), Ebenesersdóttir, S.S. (S Sunna), Elliott, J. (Joshua), Elliott, P. (Paul), Ewert, R. (Ralf), Felix, J.F. (Janine), Fischer, K. (Krista), Freedman, B.I. (Barry), Girotto, S., Goel, A. (Anuj), Gögele, M. (Martin), Goodarzi, M. (Mark), Graff, M.J. (Maud J.L.), Granot-Hershkovitz, E. (Einat), Grodstein, F. (Francine), Guarrera, S. (Simonetta), Gudbjartsson, D.F. (Daniel), Guity, K. (Kamran), Gunnarsson, B. (Bjarni), Guo, Y. (Yu), Hagenaars, S.P. (Saskia P), Haiman, C.A. (Christopher), Halevy, A. (Avner), Harris, T.B. (Tamara B), Hedayati, M. (Mehdi), Heel, D.A. (David) van, Hirata, M. (Makoto), Höfer, I. (Imo), Hsiung, C.A. (Chao Agnes), Huang, J. (Jinyan), Hung, Y.-J. (Yi-Jen), Ikram, M.A. (Arfan), Jagadeesan, A. (Anuradha), Jousilahti, P. (Pekka), Kamatani, Y. (Yoichiro), Kanai, M. (Masahiro), Kerrison, N.D. (Nicola D), Kessler, T. (Thorsten), Khaw, K.-T. (Kay-Tee), Khor, C.C., Kleijn, D.P.V. (Dominique) de, Koh, W.-P. (Woon-Puay), Kolcic, I. (Ivana), Kraft, P. (Peter), Krämer, B.K. (Bernhard), Kutalik, Z. (Zoltán), Kuusisto, J. (Johanna), Langenberg, C. (Claudia), Launer, L.J. (Lenore), Lawlor, D.A. (Debbie), Lee, I.-T. (I-Te), Lee, W.-J. (Wen-Jane), Lerch, M. (M.), Li, L. (Liming), Liu, J. (Jianjun), Loh, M. (Marie), London, S.J. (Stephanie J), Loomis, S.J. (Stephanie J.), Lu, Y. (Yingchang), Luan, J. (Jian’an), Mägi, R. (Reedik), Manichaikul, A.W. (Ani W), Manunta, P. (Paolo), Masson, G. (Gisli), Matoba, N. (Nana), Mei, X.W. (Xue W), Meisinger, C. (Christa), Meitinger, T. (Thomas), Mezzavilla, M. (Massimo), Milani, L. (Lili), Millwood, I.Y. (Iona), Momozawa, Y. (Yukihide), Moore, A. (Amy), Morange, P.-E. (P.), Moreno-Macías, H. (Hortensia), Mori, T.A. (Trevor A), Morrison, A.C. (Alanna), Muka, T. (Taulant), Murakami, Y. (Yoshinori), Murray, A.D. (Alison D), Mutsert, R. (Reneé) de, Mychaleckyj, J.C. (Josyf), Nalls, M.A. (Michael), Nauck, M. (Matthias), Neville, M.J. (Matthew), Nolte, I.M. (Ilja), Ong, K.K. (Ken K), Orozco, L. (Lorena), Padmanabhan, S. (Sandosh), Pálsson, G. (Gunnar), Palmer, C.N.A. (Colin), Penninx, B.W.J.H., Pattie, A. (Alison), Polasek, O. (Ozren), Poulter, N.R. (Neil), Pramstaller, P.P. (Peter P), Quintana-Murci, L. (Lluis), Räikkönen, K. (Katri), Ralhan, S. (Sarju), Rao, D.C. (Dabeeru C), Rheenen, W. (Wouter) van, Rich, S.S. (Stephen), Ridker, P.M. (Paul M), Rietveld, C.A. (Cornelius A), Robino, A. (Antonietta), Rooij, F.J.A. (Frank) van, Ruggiero, D., Saba, Y. (Yasaman), Sabanayagam, C. (Charumathi), Sabater-Lleal, M. (Maria), Sala, C. (Cinzia), Salomaa, V. (Veikko), Sandow, K. (Kevin), Schmidt, H. (Helena), Scott, L.J. (Laura J), Scott, W.R. (William R), Sedaghati-Khayat, B. (Bahareh), Sennblad, B. (Bengt), Setten, J. (Jessica) van, Sever, P.J. (Peter J), Sheu, W.H.-H. (Wayne H-H), Shi, Y. (Yuan), Shrestha, S. (Smeeta), Shukla, S.R. (Sharvari Rahul), Sigurdsson, J.K. (Jon K), Sikka, T.T. (Timo Tonis), Singh, J.R. (Jai Rup), Smith, B.H. (Blair), Stancáková, A. (Alena), Stanton, A. (Alice), Starr, J.M. (John), Stefansdottir, L. (Lilja), Straker, L. (Leon), Sulem, P. (Patrick), Sveinbjornsson, G. (Gardar), Swertz, M.A. (Morris A), Taylor, A.M. (Adele M), Taylor, K.D. (Kent), Terzikhan, N. (Natalie), Tham, Y.-C. (Yih-Chung), Thorleifsson, G. (Gudmar), Thorsteinsdottir, U. (Unnur), Tillander, A. (Annika), Tracy, R.P. (Russell), Tusié-Luna, T. (Teresa), Tzoulaki, I., Vaccargiu, S. (Simona), Vangipurapu, J. (Jagadish), Veldink, J.H. (Jan), Vitart, V. (Veronique), Völker, U. (Uwe), Vuoksimaa, E. (Eero), Wakil, S.M. (Salma M), Waldenberger, M. (Melanie), Wander, G.S. (Gurpreet S), Wang, Y.X. (Ya Xing), Wareham, N.J. (Nick), Wild, S.H. (Sarah), Yajnik, C.S. (Chittaranjan S), Yuan, J.-M. (Jian-Min), Zeng, L. (Lingyao), Zhang, L. (Liang), Zhou, J. (Jie), Amin, N. (Najaf), Asselbergs, F.W. (Folkert), Bakker, S.J.L. (Stephan), Becker, D.M. (Diane), Lehne, B. (Benjamin), Bennett, D.A. (David), Berg, L.H. (Leonard) van den, Berndt, S.I. (Sonja), Bharadwaj, D. (Dwaipayan), Bielak, L.F. (Lawrence F.), Bochud, M. (Murielle), Boehnke, M. (Michael), Bouchard, C. (Claude), Bradfield, J.P. (Jonathan), Brody, J.A. (Jennifer A), Campbell, A. (Archie), Carmi, S. (Shai), Caulfield, M. (Mark), Cesarini, D. (David), Chambers, J.C. (John C), Chandak, G.R. (Giriraj), Cheng, C.-Y. (Ching-Yu), Ciullo, M. (Marina), Warrington, N.M. (Nicole), Cusi, D. (Daniele), Smith, G.D. (George Davey), Deary, I.J. (Ian J), Dorajoo, R. (Rajkumar), Duijn, C.M. (Cornelia) van, Ellinghaus, D. (David), Erdmann, J. (Jeanette), Hagen, K. (Knut), Evangelou, E. (Evangelos), Evans, M.K. (Michele), Faul, J.D. (Jessica D), Feenstra, B. (Bjarke), Feitosa, M.F. (Mary Furlan), Foisy, S. (Sylvain), Franke, A. (Andre), Friedlander, Y. (Yechiel), Gasparini, P. (Paolo), Gieger, C. (Christian), Gonzalez, C. (Clicerio), Goyette, P. (Philippe), Grant, S.F.A. (Struan), Griffiths, L.R. (Lyn R), Groop, L. (Leif), Gudnason, V. (Vilmundur), Gyllensten, U. (Ulf), Hakonarson, H. (Hakon), Hamsten, A. (Anders), Harst, P. (Pim) van der, Heng, C.K. (Chew-Kiat), Hicks, A.A. (Andrew A), Hochner, H., Huikuri, H.V. (Heikki), Hunt, S.C. (Steven), Jaddoe, V.W.V. (Vincent), De Jager, P., Johannesson, M. (Magnus), Johansson, A. (Åsa), Jonas, J.B. (Jost B), Jukema, J.W. (Jan Wouter), Junttila, M.J. (Juhani), Kaprio, J. (Jaakko), Kardia, S.L.R. (Sharon), Karpe, F. (Fredrik), Kumari, M. (Meena), Laakso, M. (Markku), van der Laan, S.W. (Sander W), Lahti, J. (Jari), Laudes, M. (Matthias), Lea, R.A. (Rodney A), Lieb, W. (Wolfgang), Lumley, T. (Thomas), Martin, N.G. (Nicholas), Ye, S. (Shu), Matullo, G., McCarthy, M.I. (Mark), Medland, S.E. (Sarah), Merriman, A., Metspalu, A. (Andres), Meyer, B.F. (Brian F), Mohlke, K.L. (Karen L), Montgomery, G.W. (Grant), Mook-Kanamori, D. (Dennis), Munroe, P. (Patricia), North, K.E. (Kari), Nyholt, D.R. (Dale), O’connell, J.R. (Jeffery R), Ober, C. (Carole), Oldehinkel, A.J. (Albertine), Palmas, W. (Walter), Pasterkamp, G.G. (Gerard G), Patin, E. (Etienne), Pennell, C.E. (Craig), Perusse, L. (Louis), Peyser, P.A. (Patricia A.), Pirastu, M. (Mario), Polderman, T.J.C. (Tinca), Porteous, D.J. (David J.), Posthuma, D. (Danielle), Psaty, B.M. (Bruce M), Rioux, J.D. (John), Rivadeneira, F. (Fernando), Rotimi, C. (Charles), Rotter, J.I. (Jerome I.), Rudan, I. (Igor), Ruijter, H.M. (Hester ) den, Sanghera, D.K. (Dharambir K), Sattar, N. (Naveed), Schmidt, R. (Reinhold), Schulze, M.B. (Matthias), Schunkert, H. (Heribert), Scott, R.A. (Robert), Shuldiner, A.R. (Alan R), Sim, X. (Xueling), Small, N. (Neil), Smith, J.A. (Jennifer A), Sotoodehnia, N. (Nona), Tai, E.-S. (E-Shyong), Teumer, A. (Alexander), Timpson, N.J. (Nicholas), Toniolo, D. (Daniela), Tregouet, D.-A. (David-Alexandre), Tuomi, T. (Tiinamaija), Vollenweider, P. (Peter), Wang, C.A. (Carol A), Weir, D.R. (David R), Whitfield, J. (John), Wijmenga, C. (Cisca), Wong, T.-Y. (Tien-Yin), Wright, J. (John), Yang, J. (Jingyun), Yu, L. (Lei), Zemel, B.S. (Babette S.), Zonderman, A.B. (Alan B), Perola, M. (Markus), Magnusson, P.K. (Patrik), Uitterlinden, A.G. (André), Kooner, J.S. (Jaspal S.), Chasman, D.I. (Daniel), Loos, R.J.F. (Ruth), Franceschini, N. (Nora), Franke, L. (Lude), Haley, C. (Chris), Hayward, C. (Caroline), Walters, R.G. (Robin G), Perry, J.R.B. (John R. B.), Esko, T. (Tõnu), Helgason, A. (Agnar), Zwart, J-A. (John-Anker), Joshi, P.K. (Peter), Kubo, M. (Michiaki), Wilson, J.F. (James), Clark, D.W. (David W), Okada, Y. (Yukinori), Moore, K.H.S. (Kristjan H S), Mason, D. (Dan), Pirastu, N. (Nicola), Gandin, I. (Ilaria), Mattsson, H. (Hannele), Barnes, C.L.K. (Catriona L K), Lin, K. (Kuang), Zhao, J.H. (Jing Hua), Deelen, P. (Patrick), Rohde, R. (Rebecca), Schurmann, C. (Claudia), Guo, X. (Xiuqing), Giulianini, F. (Franco), Zhang, W. (Weihua), Medina-Gomez, M.C. (Carolina), Karlsson, R. (Robert), Bao, Y. (Yanchun), Bartz, T.M. (Traci M), Baumbach, C. (Clemens), Biino, G. (Ginevra), Bixley, M.J. (Matthew J), Brumat, M. (Marco), Chai, J.-F. (Jin-Fang), Corre, T. (Tanguy), Cousminer, D.L. (Diana), Dekker, A.M. (Annelot M), Eccles, D.A. (David A), Eijk, K.R. (Kristel) van, Fuchsberger, C. (Christian), Gao, H. (He), Germain, M. (Marine), Gordon, S.D. (Scott D.), de Haan, H.G. (Hugoline G), Harris, S.E. (Sarah), Hofer, E. (Edith), Huerta-Chagoya, A. (Alicia), Igartua, C. (Catherine), Jansen, I. (Iris), Jia, Y. (Yucheng), Kacprowski, T. (Tim), Karlsson, T. (Torgny), Kleber, M.E. (Marcus), Li, S.A. (Shengchao Alfred), Li-Gao, R. (Ruifang), Mahajan, A. (Anubha), Matsuda, K. (Koichi), Meidtner, K. (Karina), Meng, W. (Weihua), Montasser, M.E. (May E.), Most, P.J. (Peter) van der, Munz, M. (Matthias), Nutile, T. (Teresa), Palviainen, T. (Teemu), Prasad, G. (Gauri), Prasad, R.B. (Rashmi B), Priyanka, T.D.S. (Tallapragada Divya Sri), Rizzi, F. (Federica), Salvi, E. (Erika), Sapkota, B.R. (Bishwa R), Shriner, D. (Daniel), Skotte, L. (Line), Smart, M.C. (Melissa C), Smith, A.V. (Albert), Spek, A. (Ashley) van der, Spracklen, C.N. (Cassandra N), Strawbridge, R.J. (Rona), Tajuddin, S.M. (Salman M), Trompet, S. (Stella), Turman, C. (Constance), Verweij, N. (Niek), Viberti, C. (Clara), Wang, L. (Lihua), Warren, H. (Helen), Wootton, R.E. (Robyn E), Yanek, L.R. (Lisa), Yao, J. (Jie), Yousri, N.A. (Noha A), Zhao, W. (Wei), Adeyemo, A.A. (Adebowale A), Afaq, S. (Saima), Aguilar-Salinas, C.A. (Carlos Alberto), Akiyama, M. (Masato), Albert, M.L. (Matthew L), Allison, M.A. (Matthew A), Alver, M. (Maris), Aung, T. (Tin), Azizi, J. (Joshan), Bentley, A.R. (Amy), Boeing, H. (Heiner), Boerwinkle, E.A. (Eric), Borja, J.B. (Judith B), Borst, G.J. (Gert) de, Bottinger, E.P. (Erwin), Broer, L. (Linda), Campbell, H. (Harry), Chanock, S.J. (Stephen), Chee, M.-L. (Miao-Li), Chen, G. (Guanjie), Chen, Y.-D.I. (Yii-Der I), Chen, Z. (Zhengming), Chiu, Y.-F. (Yen-Feng), Cocca, M. (Massimiliano), Collins, F.S. (Francis), Concas, M.P. (Maria Pina), Corley, J. (Janie), Cugliari, G. (Giovanni), Dam, R.M. (Rob) van, Damulina, A. (Anna), Daneshpour, M.S. (Maryam S), Day, F.R. (Felix), Delgado, G., Dhana, K. (Klodian), Doney, A.S.F. (Alex), Dörr, M. (Marcus), Doumatey, A. (Ayo), Dzimiri, N. (Nduna), Ebenesersdóttir, S.S. (S Sunna), Elliott, J. (Joshua), Elliott, P. (Paul), Ewert, R. (Ralf), Felix, J.F. (Janine), Fischer, K. (Krista), Freedman, B.I. (Barry), Girotto, S., Goel, A. (Anuj), Gögele, M. (Martin), Goodarzi, M. (Mark), Graff, M.J. (Maud J.L.), Granot-Hershkovitz, E. (Einat), Grodstein, F. (Francine), Guarrera, S. (Simonetta), Gudbjartsson, D.F. (Daniel), Guity, K. (Kamran), Gunnarsson, B. (Bjarni), Guo, Y. (Yu), Hagenaars, S.P. (Saskia P), Haiman, C.A. (Christopher), Halevy, A. (Avner), Harris, T.B. (Tamara B), Hedayati, M. (Mehdi), Heel, D.A. (David) van, Hirata, M. (Makoto), Höfer, I. (Imo), Hsiung, C.A. (Chao Agnes), Huang, J. (Jinyan), Hung, Y.-J. (Yi-Jen), Ikram, M.A. (Arfan), Jagadeesan, A. (Anuradha), Jousilahti, P. (Pekka), Kamatani, Y. (Yoichiro), Kanai, M. (Masahiro), Kerrison, N.D. (Nicola D), Kessler, T. (Thorsten), Khaw, K.-T. (Kay-Tee), Khor, C.C., Kleijn, D.P.V. (Dominique) de, Koh, W.-P. (Woon-Puay), Kolcic, I. (Ivana), Kraft, P. (Peter), Krämer, B.K. (Bernhard), Kutalik, Z. (Zoltán), Kuusisto, J. (Johanna), Langenberg, C. (Claudia), Launer, L.J. (Lenore), Lawlor, D.A. (Debbie), Lee, I.-T. (I-Te), Lee, W.-J. (Wen-Jane), Lerch, M. (M.), Li, L. (Liming), Liu, J. (Jianjun), Loh, M. (Marie), London, S.J. (Stephanie J), Loomis, S.J. (Stephanie J.), Lu, Y. (Yingchang), Luan, J. (Jian’an), Mägi, R. (Reedik), Manichaikul, A.W. (Ani W), Manunta, P. (Paolo), Masson, G. (Gisli), Matoba, N. (Nana), Mei, X.W. (Xue W), Meisinger, C. (Christa), Meitinger, T. (Thomas), Mezzavilla, M. (Massimo), Milani, L. (Lili), Millwood, I.Y. (Iona), Momozawa, Y. (Yukihide), Moore, A. (Amy), Morange, P.-E. (P.), Moreno-Macías, H. (Hortensia), Mori, T.A. (Trevor A), Morrison, A.C. (Alanna), Muka, T. (Taulant), Murakami, Y. (Yoshinori), Murray, A.D. (Alison D), Mutsert, R. (Reneé) de, Mychaleckyj, J.C. (Josyf), Nalls, M.A. (Michael), Nauck, M. (Matthias), Neville, M.J. (Matthew), Nolte, I.M. (Ilja), Ong, K.K. (Ken K), Orozco, L. (Lorena), Padmanabhan, S. (Sandosh), Pálsson, G. (Gunnar), Palmer, C.N.A. (Colin), Penninx, B.W.J.H., Pattie, A. (Alison), Polasek, O. (Ozren), Poulter, N.R. (Neil), Pramstaller, P.P. (Peter P), Quintana-Murci, L. (Lluis), Räikkönen, K. (Katri), Ralhan, S. (Sarju), Rao, D.C. (Dabeeru C), Rheenen, W. (Wouter) van, Rich, S.S. (Stephen), Ridker, P.M. (Paul M), Rietveld, C.A. (Cornelius A), Robino, A. (Antonietta), Rooij, F.J.A. (Frank) van, Ruggiero, D., Saba, Y. (Yasaman), Sabanayagam, C. (Charumathi), Sabater-Lleal, M. (Maria), Sala, C. (Cinzia), Salomaa, V. (Veikko), Sandow, K. (Kevin), Schmidt, H. (Helena), Scott, L.J. (Laura J), Scott, W.R. (William R), Sedaghati-Khayat, B. (Bahareh), Sennblad, B. (Bengt), Setten, J. (Jessica) van, Sever, P.J. (Peter J), Sheu, W.H.-H. (Wayne H-H), Shi, Y. (Yuan), Shrestha, S. (Smeeta), Shukla, S.R. (Sharvari Rahul), Sigurdsson, J.K. (Jon K), Sikka, T.T. (Timo Tonis), Singh, J.R. (Jai Rup), Smith, B.H. (Blair), Stancáková, A. (Alena), Stanton, A. (Alice), Starr, J.M. (John), Stefansdottir, L. (Lilja), Straker, L. (Leon), Sulem, P. (Patrick), Sveinbjornsson, G. (Gardar), Swertz, M.A. (Morris A), Taylor, A.M. (Adele M), Taylor, K.D. (Kent), Terzikhan, N. (Natalie), Tham, Y.-C. (Yih-Chung), Thorleifsson, G. (Gudmar), Thorsteinsdottir, U. (Unnur), Tillander, A. (Annika), Tracy, R.P. (Russell), Tusié-Luna, T. (Teresa), Tzoulaki, I., Vaccargiu, S. (Simona), Vangipurapu, J. (Jagadish), Veldink, J.H. (Jan), Vitart, V. (Veronique), Völker, U. (Uwe), Vuoksimaa, E. (Eero), Wakil, S.M. (Salma M), Waldenberger, M. (Melanie), Wander, G.S. (Gurpreet S), Wang, Y.X. (Ya Xing), Wareham, N.J. (Nick), Wild, S.H. (Sarah), Yajnik, C.S. (Chittaranjan S), Yuan, J.-M. (Jian-Min), Zeng, L. (Lingyao), Zhang, L. (Liang), Zhou, J. (Jie), Amin, N. (Najaf), Asselbergs, F.W. (Folkert), Bakker, S.J.L. (Stephan), Becker, D.M. (Diane), Lehne, B. (Benjamin), Bennett, D.A. (David), Berg, L.H. (Leonard) van den, Berndt, S.I. (Sonja), Bharadwaj, D. (Dwaipayan), Bielak, L.F. (Lawrence F.), Bochud, M. (Murielle), Boehnke, M. (Michael), Bouchard, C. (Claude), Bradfield, J.P. (Jonathan), Brody, J.A. (Jennifer A), Campbell, A. (Archie), Carmi, S. (Shai), Caulfield, M. (Mark), Cesarini, D. (David), Chambers, J.C. (John C), Chandak, G.R. (Giriraj), Cheng, C.-Y. (Ching-Yu), Ciullo, M. (Marina), Warrington, N.M. (Nicole), Cusi, D. (Daniele), Smith, G.D. (George Davey), Deary, I.J. (Ian J), Dorajoo, R. (Rajkumar), Duijn, C.M. (Cornelia) van, Ellinghaus, D. (David), Erdmann, J. (Jeanette), Hagen, K. (Knut), Evangelou, E. (Evangelos), Evans, M.K. (Michele), Faul, J.D. (Jessica D), Feenstra, B. (Bjarke), Feitosa, M.F. (Mary Furlan), Foisy, S. (Sylvain), Franke, A. (Andre), Friedlander, Y. (Yechiel), Gasparini, P. (Paolo), Gieger, C. (Christian), Gonzalez, C. (Clicerio), Goyette, P. (Philippe), Grant, S.F.A. (Struan), Griffiths, L.R. (Lyn R), Groop, L. (Leif), Gudnason, V. (Vilmundur), Gyllensten, U. (Ulf), Hakonarson, H. (Hakon), Hamsten, A. (Anders), Harst, P. (Pim) van der, Heng, C.K. (Chew-Kiat), Hicks, A.A. (Andrew A), Hochner, H., Huikuri, H.V. (Heikki), Hunt, S.C. (Steven), Jaddoe, V.W.V. (Vincent), De Jager, P., Johannesson, M. (Magnus), Johansson, A. (Åsa), Jonas, J.B. (Jost B), Jukema, J.W. (Jan Wouter), Junttila, M.J. (Juhani), Kaprio, J. (Jaakko), Kardia, S.L.R. (Sharon), Karpe, F. (Fredrik), Kumari, M. (Meena), Laakso, M. (Markku), van der Laan, S.W. (Sander W), Lahti, J. (Jari), Laudes, M. (Matthias), Lea, R.A. (Rodney A), Lieb, W. (Wolfgang), Lumley, T. (Thomas), Martin, N.G. (Nicholas), Ye, S. (Shu), Matullo, G., McCarthy, M.I. (Mark), Medland, S.E. (Sarah), Merriman, A., Metspalu, A. (Andres), Meyer, B.F. (Brian F), Mohlke, K.L. (Karen L), Montgomery, G.W. (Grant), Mook-Kanamori, D. (Dennis), Munroe, P. (Patricia), North, K.E. (Kari), Nyholt, D.R. (Dale), O’connell, J.R. (Jeffery R), Ober, C. (Carole), Oldehinkel, A.J. (Albertine), Palmas, W. (Walter), Pasterkamp, G.G. (Gerard G), Patin, E. (Etienne), Pennell, C.E. (Craig), Perusse, L. (Louis), Peyser, P.A. (Patricia A.), Pirastu, M. (Mario), Polderman, T.J.C. (Tinca), Porteous, D.J. (David J.), Posthuma, D. (Danielle), Psaty, B.M. (Bruce M), Rioux, J.D. (John), Rivadeneira, F. (Fernando), Rotimi, C. (Charles), Rotter, J.I. (Jerome I.), Rudan, I. (Igor), Ruijter, H.M. (Hester ) den, Sanghera, D.K. (Dharambir K), Sattar, N. (Naveed), Schmidt, R. (Reinhold), Schulze, M.B. (Matthias), Schunkert, H. (Heribert), Scott, R.A. (Robert), Shuldiner, A.R. (Alan R), Sim, X. (Xueling), Small, N. (Neil), Smith, J.A. (Jennifer A), Sotoodehnia, N. (Nona), Tai, E.-S. (E-Shyong), Teumer, A. (Alexander), Timpson, N.J. (Nicholas), Toniolo, D. (Daniela), Tregouet, D.-A. (David-Alexandre), Tuomi, T. (Tiinamaija), Vollenweider, P. (Peter), Wang, C.A. (Carol A), Weir, D.R. (David R), Whitfield, J. (John), Wijmenga, C. (Cisca), Wong, T.-Y. (Tien-Yin), Wright, J. (John), Yang, J. (Jingyun), Yu, L. (Lei), Zemel, B.S. (Babette S.), Zonderman, A.B. (Alan B), Perola, M. (Markus), Magnusson, P.K. (Patrik), Uitterlinden, A.G. (André), Kooner, J.S. (Jaspal S.), Chasman, D.I. (Daniel), Loos, R.J.F. (Ruth), Franceschini, N. (Nora), Franke, L. (Lude), Haley, C. (Chris), Hayward, C. (Caroline), Walters, R.G. (Robin G), Perry, J.R.B. (John R. B.), Esko, T. (Tõnu), Helgason, A. (Agnar), Zwart, J-A. (John-Anker), Joshi, P.K. (Peter), Kubo, M. (Michiaki), and Wilson, J.F. (James)

Abstract

In many species, the offspring of related parents suffer reduced reproductive success, a phenomenon known as inbreeding depression. In humans, the importance of this effect has remained unclear, partly because reproduction between close relatives is both rare and frequently associated with confounding social factors. Here, using genomic inbreeding coefficients (FROH) for >1.4 million individuals, we show that FROH is significantly associated (p < 0.0005) with apparently deleterious changes in 32 out of 100 traits analysed. These changes are associated with runs of homozygosity (ROH), but not with common variant homozygosity, suggesting that genetic variants associated with inbreeding depression are predominantly rare. The effect on fertility is striking: FROH equivalent to the offspring of first cousins is associated with a 55% decrease [95% CI 44–66%] in the odds of having children. Finally, the effects of FROH are confirmed within full-sibling pairs, where the variation in FROH is independent of all environmental confounding.

Published
2019
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21. Novel metabolic indices and incident type 2 diabetes among women and men: the Rotterdam Study

Author

Brahimaj, A. (Adela), Rivadeneira, F. (Fernando), Muka, T. (Taulant), Sijbrands, E.J.G. (Eric), Franco, O.H. (Oscar), Dehghan, A. (Abbas), Kavousi, M. (Maryam), Brahimaj, A. (Adela), Rivadeneira, F. (Fernando), Muka, T. (Taulant), Sijbrands, E.J.G. (Eric), Franco, O.H. (Oscar), Dehghan, A. (Abbas), and Kavousi, M. (Maryam)

Abstract

Aims/hypothesis: Both visceral and truncal fat have been associated with metabolic disturbances. We aimed to investigate the associations of several novel metabolic indices, combining anthropom

Published
2019
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22. Socioeconomic position, lifestyle habits and biomarkers of epigenetic aging: a multi-cohort analysis.

Author

Kee F., Rosales C.O., Zhang Y., Colicino E., Dugue P.-A., Artaud F., McKay G.J., Jeong A., Mishra P.P., Elbaz A., Brenner H., Carmeli C., Voortman T., Probst-Hensch N., Lehtimaki T., Elliot P., Stringhini S., Vineis P., Polidoro S., Fiorito G., McCrory C., Robinson O., Nost T.H., Krogh V., Panico S., Sacerdote C., Tumino R., Palli D., Matullo G., Guarrera S., Gandini M., Bochud M., Dermitzakis E., Muka T., Schwartz J., Vokonas P.S., Just A., Hodge A.M., Giles G.G., Southey M.C., Hurme M.A., Young I., McKnight A.J., Kunze S., Waldenberger M., Peters A., Schwettmann L., Lund E., Baccarelli A., Milne R.L., Kenny R.A., Kee F., Rosales C.O., Zhang Y., Colicino E., Dugue P.-A., Artaud F., McKay G.J., Jeong A., Mishra P.P., Elbaz A., Brenner H., Carmeli C., Voortman T., Probst-Hensch N., Lehtimaki T., Elliot P., Stringhini S., Vineis P., Polidoro S., Fiorito G., McCrory C., Robinson O., Nost T.H., Krogh V., Panico S., Sacerdote C., Tumino R., Palli D., Matullo G., Guarrera S., Gandini M., Bochud M., Dermitzakis E., Muka T., Schwartz J., Vokonas P.S., Just A., Hodge A.M., Giles G.G., Southey M.C., Hurme M.A., Young I., McKnight A.J., Kunze S., Waldenberger M., Peters A., Schwettmann L., Lund E., Baccarelli A., Milne R.L., and Kenny R.A.

Abstract

Differences in health status by socioeconomic position (SEP) tend to be more evident at older ages, suggesting the involvement of a biological mechanism responsive to the accumulation of deleterious exposures across the lifespan. DNA methylation (DNAm) has been proposed as a biomarker of biological aging that conserves memory of endogenous and exogenous stress during life.We examined the association of education level, as an indicator of SEP, and lifestyle-related variables with four biomarkers of age-dependent DNAm dysregulation: the total number of stochastic epigenetic mutations (SEMs) and three epigenetic clocks (Horvath, Hannum and Levine), in 18 cohorts spanning 12 countries.The four biological aging biomarkers were associated with education and different sets of risk factors independently, and the magnitude of the effects differed depending on the biomarker and the predictor. On average, the effect of low education on epigenetic aging was comparable with those of other lifestyle-related risk factors (obesity, alcohol intake), with the exception of smoking, which had a significantly stronger effect.Our study shows that low education is an independent predictor of accelerated biological (epigenetic) aging and that epigenetic clocks appear to be good candidates for disentangling the biological pathways underlying social inequalities in healthy aging and longevity.

Published
2019

23. Socioeconomic position, lifestyle habits and biomarkers of epigenetic aging: a multi-cohort analysis

Author

Fiorito, G, McCrory, C, Robinson, O, Carmeli, C, Rosales, CO, Zhang, Y, Colicino, E, Dugue, P-A, Artaud, F, Mckay, GJ, Jeong, A, Mishra, PP, Nost, TH, Krogh, V, Panico, S, Sacerdote, C, Tumino, R, Palli, D, Matullo, G, Guarrera, S, Gandini, M, Bochud, M, Dermitzakis, E, Muka, T, Schwartz, J, Vokonas, PS, Just, A, Hodge, AM, Giles, GG, Southey, MC, Hurme, MA, Young, I, McKnight, AJ, Kunze, S, Waldenberger, M, Peters, A, Schwettmann, L, Lund, E, Baccarelli, A, Milne, RL, Kenny, RA, Elbaz, A, Brenner, H, Kee, F, Voortman, T, Probst-Hensch, N, Lehtimaki, T, Elliot, P, Stringhini, S, Vineis, P, Polidoro, S, Alberts, J, Alenius, H, Avendano, M, Baltar, V, Bartley, M, Barros, H, Bellone, M, Berger, E, Blane, D, Candiani, G, Carra, L, Castagne, R, Chadeau-Hyam, M, Cima, S, Clavel-Chapelon, F, Costa, G, Courtin, E, Delpierre, C, D'Errico, A, Manolis, Dermitzakis, Elovainio, M, Elliott, P, Fagherazzi, G, Fraga, S, Gares, V, Gerbouin-Rerolle, P, Giles, G, Goldberg, M, Greco, D, Guessous, I, Haba-Rubio, J, Heinzer, R, Hodge, A, Joost, S, Karimi, M, Kelly-Irving, M, Kahonen, M, Karisola, P, Khenissi, L, Kivimaki, M, Laine, J, Lang, T, Laurent, A, Layte, R, Lepage, B, Lorsch, D, MacGuire, F, Machell, G, Mackenbach, J, Marmot, M, de Mestral, C, Miller, C, Milne, R, Muennig, P, Nusselder, W, Petrovic, D, Lourdes, Pilapil, Preisig, M, Pulkki-Raback, L, Raitakari, O, Ribeiro, AI, Ricceri, F, Recalcati, P, Reinhard, E, Valverde, JR, Saba, S, Santegoets, F, Satolli, R, Simmons, T, Severi, G, Shipley, MJ, Tabak, A, Terhi, V, Tieulent, J, Vaccarella, S, Vigna-Taglianti, F, Vollenweider, P, Vuilleumier, N, Zins, M, Fiorito, G, McCrory, C, Robinson, O, Carmeli, C, Rosales, CO, Zhang, Y, Colicino, E, Dugue, P-A, Artaud, F, Mckay, GJ, Jeong, A, Mishra, PP, Nost, TH, Krogh, V, Panico, S, Sacerdote, C, Tumino, R, Palli, D, Matullo, G, Guarrera, S, Gandini, M, Bochud, M, Dermitzakis, E, Muka, T, Schwartz, J, Vokonas, PS, Just, A, Hodge, AM, Giles, GG, Southey, MC, Hurme, MA, Young, I, McKnight, AJ, Kunze, S, Waldenberger, M, Peters, A, Schwettmann, L, Lund, E, Baccarelli, A, Milne, RL, Kenny, RA, Elbaz, A, Brenner, H, Kee, F, Voortman, T, Probst-Hensch, N, Lehtimaki, T, Elliot, P, Stringhini, S, Vineis, P, Polidoro, S, Alberts, J, Alenius, H, Avendano, M, Baltar, V, Bartley, M, Barros, H, Bellone, M, Berger, E, Blane, D, Candiani, G, Carra, L, Castagne, R, Chadeau-Hyam, M, Cima, S, Clavel-Chapelon, F, Costa, G, Courtin, E, Delpierre, C, D'Errico, A, Manolis, Dermitzakis, Elovainio, M, Elliott, P, Fagherazzi, G, Fraga, S, Gares, V, Gerbouin-Rerolle, P, Giles, G, Goldberg, M, Greco, D, Guessous, I, Haba-Rubio, J, Heinzer, R, Hodge, A, Joost, S, Karimi, M, Kelly-Irving, M, Kahonen, M, Karisola, P, Khenissi, L, Kivimaki, M, Laine, J, Lang, T, Laurent, A, Layte, R, Lepage, B, Lorsch, D, MacGuire, F, Machell, G, Mackenbach, J, Marmot, M, de Mestral, C, Miller, C, Milne, R, Muennig, P, Nusselder, W, Petrovic, D, Lourdes, Pilapil, Preisig, M, Pulkki-Raback, L, Raitakari, O, Ribeiro, AI, Ricceri, F, Recalcati, P, Reinhard, E, Valverde, JR, Saba, S, Santegoets, F, Satolli, R, Simmons, T, Severi, G, Shipley, MJ, Tabak, A, Terhi, V, Tieulent, J, Vaccarella, S, Vigna-Taglianti, F, Vollenweider, P, Vuilleumier, N, and Zins, M

Abstract

Differences in health status by socioeconomic position (SEP) tend to be more evident at older ages, suggesting the involvement of a biological mechanism responsive to the accumulation of deleterious exposures across the lifespan. DNA methylation (DNAm) has been proposed as a biomarker of biological aging that conserves memory of endogenous and exogenous stress during life.We examined the association of education level, as an indicator of SEP, and lifestyle-related variables with four biomarkers of age-dependent DNAm dysregulation: the total number of stochastic epigenetic mutations (SEMs) and three epigenetic clocks (Horvath, Hannum and Levine), in 18 cohorts spanning 12 countries.The four biological aging biomarkers were associated with education and different sets of risk factors independently, and the magnitude of the effects differed depending on the biomarker and the predictor. On average, the effect of low education on epigenetic aging was comparable with those of other lifestyle-related risk factors (obesity, alcohol intake), with the exception of smoking, which had a significantly stronger effect.Our study shows that low education is an independent predictor of accelerated biological (epigenetic) aging and that epigenetic clocks appear to be good candidates for disentangling the biological pathways underlying social inequalities in healthy aging and longevity.

Published
2019

24. Associations of autozygosity with a broad range of human phenotypes

Author

Clark, D. W. (David W.), Okada, Y. (Yukinori), Moore, K. H. (Kristjan H. S.), Mason, D. (Dan), Pirastu, N. (Nicola), Gandin, I. (Ilaria), Mattsson, H. (Hannele), Barnes, C. L. (Catriona L. K.), Lin, K. (Kuang), Zhao, J. H. (Jing Hua), Deelen, P. (Patrick), Rohde, R. (Rebecca), Schurmann, C. (Claudia), Guo, X. (Xiuqing), Giulianini, F. (Franco), Zhang, W. (Weihua), Medina-Gomez, C. (Carolina), Karlsson, R. (Robert), Bao, Y. (Yanchun), Bartz, T. M. (Traci M.), Baumbach, C. (Clemens), Biino, G. (Ginevra), Bixley, M. J. (Matthew J.), Brumat, M. (Marco), Chai, J.-F. (Jin-Fang), Corre, T. (Tanguy), Cousminer, D. L. (Diana L.), Dekker, A. M. (Annelot M.), Eccles, D. A. (David A.), Van Eijk, K. R. (Kristel R.), Fuchsberger, C. (Christian), Gao, H. (He), Germain, M. (Marine), Gordon, S. D. (Scott D.), de Haan, H. G. (Hugoline G.), Harris, S. E. (Sarah E.), Hofer, E. (Edith), Huerta-Chagoya, A. (Alicia), Igartua, C. (Catherine), Jansen, I. E. (Iris E.), Jia, Y. (Yucheng), Kacprowski, T. (Tim), Karlsson, T. (Torgny), Kleber, M. E. (Marcus E.), Li, S. A. (Shengchao Alfred), Li-Gao, R. (Ruifang), Mahajan, A. (Anubha), Matsuda, K. (Koichi), Meidtner, K. (Karina), Meng, W. (Weihua), Montasser, M. E. (May E.), van der Most, P. J. (Peter J.), Munz, M. (Matthias), Nutile, T. (Teresa), Palviainen, T. (Teemu), Prasad, G. (Gauri), Prasad, R. B. (Rashmi B.), Priyanka, T. D. (Tallapragada Divya Sri), Rizzi, F. (Federica), Salvi, E. (Erika), Sapkota, B. R. (Bishwa R.), Shriner, D. (Daniel), Skotte, L. (Line), Smart, M. C. (Melissa C.), Smith, A. V. (Albert Vernon), van der Spek, A. (Ashley), Spracklen, C. N. (Cassandra N.), Strawbridge, R. J. (Rona J.), Tajuddin, S. M. (Salman M.), Trompet, S. (Stella), Turman, C. (Constance), Verweij, N. (Niek), Viberti, C. (Clara), Wang, L. (Lihua), Warren, H. R. (Helen R.), Wootton, R. E. (Robyn E.), Yanek, L. R. (Lisa R.), Yao, J. (Jie), Yousri, N. A. (Noha A.), Zhao, W. (Wei), Adeyemo, A. A. (Adebowale A.), Afaq, S. (Saima), Alberto Aguilar-Salinas, C. (Carlos), Akiyama, M. (Masato), Albert, M. L. (Matthew L.), Allison, M. A. (Matthew A.), Alver, M. (Maris), Aung, T. (Tin), Azizi, F. (Fereidoun), Bentley, A. R. (Amy R.), Boeing, H. (Heiner), Boerwinkle, E. (Eric), Borja, J. B. (Judith B.), de Borst, G. J. (Gert J.), Bottinger, E. P. (Erwin P.), Broer, L. (Linda), Campbell, H. (Harry), Chanock, S. (Stephen), Chee, M.-L. (Miao-Li), Chen, G. (Guanjie), Chen, Y. I. (Yii-Der I.), Chen, Z. (Zhengming), Chiu, Y.-F. (Yen-Feng), Cocca, M. (Massimiliano), Collins, F. S. (Francis S.), Concas, M. P. (Maria Pina), Corley, J. (Janie), Cugliari, G. (Giovanni), Van Dam, R. M. (Rob M.), Damulina, A. (Anna), Daneshpour, M. S. (Maryam S.), Day, F. R. (Felix R.), Delgado, G. E. (Graciela E.), Dhana, K. (Klodian), Doney, A. S. (Alexander S. F.), Doerr, M. (Marcus), Doumatey, A. P. (Ayo P.), Dzimiri, N. (Nduna), Ebenesersdottir, S. S. (S. Sunna), Elliott, J. (Joshua), Elliott, P. (Paul), Ewert, R. (Ralf), Felix, J. F. (Janine F.), Fischer, K. (Krista), Freedman, B. I. (Barry I.), Girotto, G. (Giorgia), Goel, A. (Anuj), Gogele, M. (Martin), Goodarzi, M. O. (Mark O.), Graff, M. (Mariaelisa), Granot-Hershkovitz, E. (Einat), Grodstein, F. (Francine), Guarrera, S. (Simonetta), Gudbjartsson, D. F. (Daniel F.), Guity, K. (Kamran), Gunnarsson, B. (Bjarni), Guo, Y. (Yu), Hagenaars, S. P. (Saskia P.), Haiman, C. A. (Christopher A.), Halevy, A. (Avner), Harris, T. B. (Tamara B.), Hedayati, M. (Mehdi), van Heel, D. A. (David A.), Hirata, M. (Makoto), Hofer, I. (Imo), Hsiung, C. A. (Chao Agnes), Huang, J. (Jinyan), Hung, Y.-J. (Yi-Jen), Ikram, M. A. (M. Arfan), Jagadeesan, A. (Anuradha), Jousilahti, P. (Pekka), Kamatani, Y. (Yoichiro), Kanai, M. (Masahiro), Kerrison, N. D. (Nicola D.), Kessler, T. (Thorsten), Khaw, K.-T. (Kay-Tee), Khor, C. C. (Chiea Chuen), de Kleijn, D. P. (Dominique P. V.), Koh, W.-P. (Woon-Puay), Kolcic, I. (Ivana), Kraft, P. (Peter), Kramer, B. K. (Bernhard K.), Kutalik, Z. (Zoltan), Kuusisto, J. (Johanna), Langenberg, C. (Claudia), Launer, L. J. (Lenore J.), Lawlor, D. A. (Deborah A.), Lee, I.-T. (I-Te), Lee, W.-J. (Wen-Jane), Lerch, M. M. (Markus M.), Li, L. (Liming), Liu, J. (Jianjun), Loh, M. (Marie), London, S. J. (Stephanie J.), Loomis, S. (Stephanie), Lu, Y. (Yingchang), Luan, J. (Jian'an), Magi, R. (Reedik), Manichaikul, A. W. (Ani W.), Manunta, P. (Paolo), Masson, G. (Gisli), Matoba, N. (Nana), Mei, X. W. (Xue W.), Meisinger, C. (Christa), Meitinger, T. (Thomas), Mezzavilla, M. (Massimo), Milani, L. (Lili), Millwood, I. Y. (Iona Y.), Momozawa, Y. (Yukihide), Moore, A. (Amy), Morange, P.-E. (Pierre-Emmanuel), Moreno-Macias, H. (Hortensia), Mori, T. A. (Trevor A.), Morrison, A. C. (Alanna C.), Muka, T. (Taulant), Murakami, Y. (Yoshinori), Murray, A. D. (Alison D.), de Mutsert, R. (Renee), Mychaleckyj, J. C. (Josyf C.), Nalls, M. A. (Mike A.), Nauck, M. (Matthias), Neville, M. J. (Matt J.), Nolte, I. M. (Ilja M.), Ong, K. K. (Ken K.), Orozco, L. (Lorena), Padmanabhan, S. (Sandosh), Palsson, G. (Gunnar), Pankow, J. S. (James S.), Pattaro, C. (Cristian), Pattie, A. (Alison), Polasek, O. (Ozren), Poulter, N. (Neil), Pramstaller, P. P. (Peter P.), Quintana-Murci, L. (Lluis), Raikkonen, K. (Katri), Ralhan, S. (Sarju), Rao, D. C. (Dabeeru C.), van Rheenen, W. (Wouter), Rich, S. S. (Stephen S.), Ridker, P. M. (Paul M.), Rietveld, C. A. (Cornelius A.), Robino, A. (Antonietta), van Rooij, F. J. (Frank J. A.), Ruggiero, D. (Daniela), Saba, Y. (Yasaman), Sabanayagam, C. (Charumathi), Sabater-Lleal, M. (Maria), Felicita Sala, C. (Cinzia), Salomaa, V. (Veikko), Sandow, K. (Kevin), Schmidt, H. (Helena), Scott, L. J. (Laura J.), Scott, W. R. (William R.), Sedaghati-Khayat, B. (Bahareh), Sennblad, B. (Bengt), van Setten, J. (Jessica), Sever, P. J. (Peter J.), Sheu, W. H. (Wayne H-H), Shi, Y. (Yuan), Shrestha, S. (Smeeta), Shukla, S. R. (Sharvari Rahul), Sigurdsson, J. K. (Jon K.), Sikka, T. T. (Timo Tonis), Singh, J. R. (Jai Rup), Smith, B. H. (Blair H.), Stancakova, A. (Alena), Stanton, A. (Alice), Starr, J. M. (John M.), Stefansdottir, L. (Lilja), Straker, L. (Leon), Sulem, P. (Patrick), Sveinbjornsson, G. (Gardar), Swertz, M. A. (Morris A.), Taylor, A. M. (Adele M.), Taylor, K. D. (Kent D.), Terzikhan, N. (Natalie), Tham, Y.-C. (Yih-Chung), Thorleifsson, G. (Gudmar), Thorsteinsdottir, U. (Unnur), Tillander, A. (Annika), Tracy, R. P. (Russell P.), Tusie-Luna, T. (Teresa), Tzoulaki, I. (Ioanna), Vaccargiu, S. (Simona), Vangipurapu, J. (Jagadish), Veldink, J. H. (Jan H.), Vitart, V. (Veronique), Volker, U. (Uwe), Vuoksimaa, E. (Eero), Wakil, S. M. (Salma M.), Waldenberger, M. (Melanie), Wander, G. S. (Gurpreet S.), Wang, Y. X. (Ya Xing), Wareham, N. J. (Nicholas J.), Wild, S. (Sarah), Yajnik, C. S. (Chittaranjan S.), Yuan, J.-M. (Jian-Min), Zeng, L. (Lingyao), Zhang, L. (Liang), Zhou, J. (Jie), Amin, N. (Najaf), Asselbergs, F. W. (Folkert W.), Bakker, S. J. (Stephan J. L.), Becker, D. M. (Diane M.), Lehne, B. (Benjamin), Bennett, D. A. (David A.), van den Berg, L. H. (Leonard H.), Berndt, S. I. (Sonja I.), Bharadwaj, D. (Dwaipayan), Bielak, L. F. (Lawrence F.), Bochud, M. (Murielle), Boehnke, M. (Mike), Bouchard, C. (Claude), Bradfield, J. P. (Jonathan P.), Brody, J. A. (Jennifer A.), Campbell, A. (Archie), Carmi, S. (Shai), Caulfield, M. J. (Mark J.), Cesarini, D. (David), Chambers, J. C. (John C.), Chandak, G. R. (Giriraj Ratan), Cheng, C.-Y. (Ching-Yu), Ciullo, M. (Marina), Cornelis, M. (Marilyn), Cusi, D. (Daniele), Smith, G. D. (George Davey), Deary, I. J. (Ian J.), Dorajoo, R. (Rajkumar), van Duijn, C. M. (Cornelia M.), Ellinghaus, D. (David), Erdmann, J. (Jeanette), Eriksson, J. G. (Johan G.), Evangelou, E. (Evangelos), Evans, M. K. (Michele K.), Faul, J. D. (Jessica D.), Feenstra, B. (Bjarke), Feitosa, M. (Mary), Foisy, S. (Sylvain), Franke, A. (Andre), Friedlander, Y. (Yechiel), Gasparini, P. (Paolo), Gieger, C. (Christian), Gonzalez, C. (Clicerio), Goyette, P. (Philippe), Grant, S. F. (Struan F. A.), Griffiths, L. R. (Lyn R.), Groop, L. (Leif), Gudnason, V. (Vilmundur), Gyllensten, U. (Ulf), Hakonarson, H. (Hakon), Hamsten, A. (Anders), van der Harst, P. (Pim), Heng, C.-K. (Chew-Kiat), Hicks, A. A. (Andrew A.), Hochner, H. (Hagit), Huikuri, H. (Heikki), Hunt, S. C. (Steven C.), Jaddoe, V. W. (Vincent W. V.), De Jager, P. L. (Philip L.), Johannesson, M. (Magnus), Johansson, A. (Asa), Jonas, J. B. (Jost B.), Jukema, J. W. (J. Wouter), Junttila, J. (Juhani), Kaprio, J. (Jaakko), Kardia, S. L. (Sharon L. R.), Karpe, F. (Fredrik), Kumari, M. (Meena), Laakso, M. (Markku), van der Laan, S. W. (Sander W.), Lahti, J. (Jari), Laudes, M. (Matthias), Lea, R. A. (Rodney A.), Lieb, W. (Wolfgang), Lumley, T. (Thomas), Martin, N. G. (Nicholas G.), Marz, W. (Winfried), Matullo, G. (Giuseppe), McCarthy, M. I. (Mark I.), Medland, S. E. (Sarah E.), Merriman, T. R. (Tony R.), Metspalu, A. (Andres), Meyer, B. F. (Brian F.), Mohlke, K. L. (Karen L.), Montgomery, G. W. (Grant W.), Mook-Kanamori, D. (Dennis), Munroe, P. B. (Patricia B.), North, K. E. (Kari E.), Nyholt, D. R. (Dale R.), O'connell, J. R. (Jeffery R.), Ober, C. (Carole), Oldehinkel, A. J. (Albertine J.), Palmas, W. (Walter), Palmer, C. (Colin), Pasterkamp, G. G. (Gerard G.), Patin, E. (Etienne), Pennell, C. E. (Craig E.), Perusse, L. (Louis), Peyser, P. A. (Patricia A.), Pirastu, M. (Mario), Polderman, T. J. (Tinca J. C.), Porteous, D. J. (David J.), Posthuma, D. (Danielle), Psaty, B. M. (Bruce M.), Rioux, J. D. (John D.), Rivadeneira, F. (Fernando), Rotimi, C. (Charles), Rotter, J. I. (Jerome I.), Rudan, I. (Igor), Den Ruijter, H. M. (Hester M.), Sanghera, D. K. (Dharambir K.), Sattar, N. (Naveed), Schmidt, R. (Reinhold), Schulze, M. B. (Matthias B.), Schunkert, H. (Heribert), Scott, R. A. (Robert A.), Shuldiner, A. R. (Alan R.), Sim, X. (Xueling), Small, N. (Neil), Smith, J. A. (Jennifer A.), Sotoodehnia, N. (Nona), Tai, E.-S. (E-Shyong), Teumer, A. (Alexander), Timpson, N. J. (Nicholas J.), Toniolo, D. (Daniela), Tregouet, D.-A. (David-Alexandre), Tuomi, T. (Tiinamaija), Vollenweider, P. (Peter), Wang, C. A. (Carol A.), Weir, D. R. (David R.), Whitfield, J. B. (John B.), Wijmenga, C. (Cisca), Wong, T.-Y. (Tien-Yin), Wright, J. (John), Yang, J. (Jingyun), Yu, L. (Lei), Zemel, B. S. (Babette S.), Zonderman, A. B. (Alan B.), Perola, M. (Markus), Magnusson, P. K. (Patrik K. E.), Uitterlinden, A. G. (Andre G.), Kooner, J. S. (Jaspal S.), Chasman, D. I. (Daniel I.), Loos, R. J. (Ruth J. F.), Franceschini, N. (Nora), Franke, L. (Lude), Haley, C. S. (Chris S.), Hayward, C. (Caroline), Walters, R. G. (Robin G.), Perry, J. R. (John R. B.), Esko, T. (Tonu), Helgason, A. (Agnar), Stefansson, K. (Kari), Joshi, P. K. (Peter K.), Kubo, M. (Michiaki), Wilson, J. F. (James F.), Clark, D. W. (David W.), Okada, Y. (Yukinori), Moore, K. H. (Kristjan H. S.), Mason, D. (Dan), Pirastu, N. (Nicola), Gandin, I. (Ilaria), Mattsson, H. (Hannele), Barnes, C. L. (Catriona L. K.), Lin, K. (Kuang), Zhao, J. H. (Jing Hua), Deelen, P. (Patrick), Rohde, R. (Rebecca), Schurmann, C. (Claudia), Guo, X. (Xiuqing), Giulianini, F. (Franco), Zhang, W. (Weihua), Medina-Gomez, C. (Carolina), Karlsson, R. (Robert), Bao, Y. (Yanchun), Bartz, T. M. (Traci M.), Baumbach, C. (Clemens), Biino, G. (Ginevra), Bixley, M. J. (Matthew J.), Brumat, M. (Marco), Chai, J.-F. (Jin-Fang), Corre, T. (Tanguy), Cousminer, D. L. (Diana L.), Dekker, A. M. (Annelot M.), Eccles, D. A. (David A.), Van Eijk, K. R. (Kristel R.), Fuchsberger, C. (Christian), Gao, H. (He), Germain, M. (Marine), Gordon, S. D. (Scott D.), de Haan, H. G. (Hugoline G.), Harris, S. E. (Sarah E.), Hofer, E. (Edith), Huerta-Chagoya, A. (Alicia), Igartua, C. (Catherine), Jansen, I. E. (Iris E.), Jia, Y. (Yucheng), Kacprowski, T. (Tim), Karlsson, T. (Torgny), Kleber, M. E. (Marcus E.), Li, S. A. (Shengchao Alfred), Li-Gao, R. (Ruifang), Mahajan, A. (Anubha), Matsuda, K. (Koichi), Meidtner, K. (Karina), Meng, W. (Weihua), Montasser, M. E. (May E.), van der Most, P. J. (Peter J.), Munz, M. (Matthias), Nutile, T. (Teresa), Palviainen, T. (Teemu), Prasad, G. (Gauri), Prasad, R. B. (Rashmi B.), Priyanka, T. D. (Tallapragada Divya Sri), Rizzi, F. (Federica), Salvi, E. (Erika), Sapkota, B. R. (Bishwa R.), Shriner, D. (Daniel), Skotte, L. (Line), Smart, M. C. (Melissa C.), Smith, A. V. (Albert Vernon), van der Spek, A. (Ashley), Spracklen, C. N. (Cassandra N.), Strawbridge, R. J. (Rona J.), Tajuddin, S. M. (Salman M.), Trompet, S. (Stella), Turman, C. (Constance), Verweij, N. (Niek), Viberti, C. (Clara), Wang, L. (Lihua), Warren, H. R. (Helen R.), Wootton, R. E. (Robyn E.), Yanek, L. R. (Lisa R.), Yao, J. (Jie), Yousri, N. A. (Noha A.), Zhao, W. (Wei), Adeyemo, A. A. (Adebowale A.), Afaq, S. (Saima), Alberto Aguilar-Salinas, C. (Carlos), Akiyama, M. (Masato), Albert, M. L. (Matthew L.), Allison, M. A. (Matthew A.), Alver, M. (Maris), Aung, T. (Tin), Azizi, F. (Fereidoun), Bentley, A. R. (Amy R.), Boeing, H. (Heiner), Boerwinkle, E. (Eric), Borja, J. B. (Judith B.), de Borst, G. J. (Gert J.), Bottinger, E. P. (Erwin P.), Broer, L. (Linda), Campbell, H. (Harry), Chanock, S. (Stephen), Chee, M.-L. (Miao-Li), Chen, G. (Guanjie), Chen, Y. I. (Yii-Der I.), Chen, Z. (Zhengming), Chiu, Y.-F. (Yen-Feng), Cocca, M. (Massimiliano), Collins, F. S. (Francis S.), Concas, M. P. (Maria Pina), Corley, J. (Janie), Cugliari, G. (Giovanni), Van Dam, R. M. (Rob M.), Damulina, A. (Anna), Daneshpour, M. S. (Maryam S.), Day, F. R. (Felix R.), Delgado, G. E. (Graciela E.), Dhana, K. (Klodian), Doney, A. S. (Alexander S. F.), Doerr, M. (Marcus), Doumatey, A. P. (Ayo P.), Dzimiri, N. (Nduna), Ebenesersdottir, S. S. (S. Sunna), Elliott, J. (Joshua), Elliott, P. (Paul), Ewert, R. (Ralf), Felix, J. F. (Janine F.), Fischer, K. (Krista), Freedman, B. I. (Barry I.), Girotto, G. (Giorgia), Goel, A. (Anuj), Gogele, M. (Martin), Goodarzi, M. O. (Mark O.), Graff, M. (Mariaelisa), Granot-Hershkovitz, E. (Einat), Grodstein, F. (Francine), Guarrera, S. (Simonetta), Gudbjartsson, D. F. (Daniel F.), Guity, K. (Kamran), Gunnarsson, B. (Bjarni), Guo, Y. (Yu), Hagenaars, S. P. (Saskia P.), Haiman, C. A. (Christopher A.), Halevy, A. (Avner), Harris, T. B. (Tamara B.), Hedayati, M. (Mehdi), van Heel, D. A. (David A.), Hirata, M. (Makoto), Hofer, I. (Imo), Hsiung, C. A. (Chao Agnes), Huang, J. (Jinyan), Hung, Y.-J. (Yi-Jen), Ikram, M. A. (M. Arfan), Jagadeesan, A. (Anuradha), Jousilahti, P. (Pekka), Kamatani, Y. (Yoichiro), Kanai, M. (Masahiro), Kerrison, N. D. (Nicola D.), Kessler, T. (Thorsten), Khaw, K.-T. (Kay-Tee), Khor, C. C. (Chiea Chuen), de Kleijn, D. P. (Dominique P. V.), Koh, W.-P. (Woon-Puay), Kolcic, I. (Ivana), Kraft, P. (Peter), Kramer, B. K. (Bernhard K.), Kutalik, Z. (Zoltan), Kuusisto, J. (Johanna), Langenberg, C. (Claudia), Launer, L. J. (Lenore J.), Lawlor, D. A. (Deborah A.), Lee, I.-T. (I-Te), Lee, W.-J. (Wen-Jane), Lerch, M. M. (Markus M.), Li, L. (Liming), Liu, J. (Jianjun), Loh, M. (Marie), London, S. J. (Stephanie J.), Loomis, S. (Stephanie), Lu, Y. (Yingchang), Luan, J. (Jian'an), Magi, R. (Reedik), Manichaikul, A. W. (Ani W.), Manunta, P. (Paolo), Masson, G. (Gisli), Matoba, N. (Nana), Mei, X. W. (Xue W.), Meisinger, C. (Christa), Meitinger, T. (Thomas), Mezzavilla, M. (Massimo), Milani, L. (Lili), Millwood, I. Y. (Iona Y.), Momozawa, Y. (Yukihide), Moore, A. (Amy), Morange, P.-E. (Pierre-Emmanuel), Moreno-Macias, H. (Hortensia), Mori, T. A. (Trevor A.), Morrison, A. C. (Alanna C.), Muka, T. (Taulant), Murakami, Y. (Yoshinori), Murray, A. D. (Alison D.), de Mutsert, R. (Renee), Mychaleckyj, J. C. (Josyf C.), Nalls, M. A. (Mike A.), Nauck, M. (Matthias), Neville, M. J. (Matt J.), Nolte, I. M. (Ilja M.), Ong, K. K. (Ken K.), Orozco, L. (Lorena), Padmanabhan, S. (Sandosh), Palsson, G. (Gunnar), Pankow, J. S. (James S.), Pattaro, C. (Cristian), Pattie, A. (Alison), Polasek, O. (Ozren), Poulter, N. (Neil), Pramstaller, P. P. (Peter P.), Quintana-Murci, L. (Lluis), Raikkonen, K. (Katri), Ralhan, S. (Sarju), Rao, D. C. (Dabeeru C.), van Rheenen, W. (Wouter), Rich, S. S. (Stephen S.), Ridker, P. M. (Paul M.), Rietveld, C. A. (Cornelius A.), Robino, A. (Antonietta), van Rooij, F. J. (Frank J. A.), Ruggiero, D. (Daniela), Saba, Y. (Yasaman), Sabanayagam, C. (Charumathi), Sabater-Lleal, M. (Maria), Felicita Sala, C. (Cinzia), Salomaa, V. (Veikko), Sandow, K. (Kevin), Schmidt, H. (Helena), Scott, L. J. (Laura J.), Scott, W. R. (William R.), Sedaghati-Khayat, B. (Bahareh), Sennblad, B. (Bengt), van Setten, J. (Jessica), Sever, P. J. (Peter J.), Sheu, W. H. (Wayne H-H), Shi, Y. (Yuan), Shrestha, S. (Smeeta), Shukla, S. R. (Sharvari Rahul), Sigurdsson, J. K. (Jon K.), Sikka, T. T. (Timo Tonis), Singh, J. R. (Jai Rup), Smith, B. H. (Blair H.), Stancakova, A. (Alena), Stanton, A. (Alice), Starr, J. M. (John M.), Stefansdottir, L. (Lilja), Straker, L. (Leon), Sulem, P. (Patrick), Sveinbjornsson, G. (Gardar), Swertz, M. A. (Morris A.), Taylor, A. M. (Adele M.), Taylor, K. D. (Kent D.), Terzikhan, N. (Natalie), Tham, Y.-C. (Yih-Chung), Thorleifsson, G. (Gudmar), Thorsteinsdottir, U. (Unnur), Tillander, A. (Annika), Tracy, R. P. (Russell P.), Tusie-Luna, T. (Teresa), Tzoulaki, I. (Ioanna), Vaccargiu, S. (Simona), Vangipurapu, J. (Jagadish), Veldink, J. H. (Jan H.), Vitart, V. (Veronique), Volker, U. (Uwe), Vuoksimaa, E. (Eero), Wakil, S. M. (Salma M.), Waldenberger, M. (Melanie), Wander, G. S. (Gurpreet S.), Wang, Y. X. (Ya Xing), Wareham, N. J. (Nicholas J.), Wild, S. (Sarah), Yajnik, C. S. (Chittaranjan S.), Yuan, J.-M. (Jian-Min), Zeng, L. (Lingyao), Zhang, L. (Liang), Zhou, J. (Jie), Amin, N. (Najaf), Asselbergs, F. W. (Folkert W.), Bakker, S. J. (Stephan J. L.), Becker, D. M. (Diane M.), Lehne, B. (Benjamin), Bennett, D. A. (David A.), van den Berg, L. H. (Leonard H.), Berndt, S. I. (Sonja I.), Bharadwaj, D. (Dwaipayan), Bielak, L. F. (Lawrence F.), Bochud, M. (Murielle), Boehnke, M. (Mike), Bouchard, C. (Claude), Bradfield, J. P. (Jonathan P.), Brody, J. A. (Jennifer A.), Campbell, A. (Archie), Carmi, S. (Shai), Caulfield, M. J. (Mark J.), Cesarini, D. (David), Chambers, J. C. (John C.), Chandak, G. R. (Giriraj Ratan), Cheng, C.-Y. (Ching-Yu), Ciullo, M. (Marina), Cornelis, M. (Marilyn), Cusi, D. (Daniele), Smith, G. D. (George Davey), Deary, I. J. (Ian J.), Dorajoo, R. (Rajkumar), van Duijn, C. M. (Cornelia M.), Ellinghaus, D. (David), Erdmann, J. (Jeanette), Eriksson, J. G. (Johan G.), Evangelou, E. (Evangelos), Evans, M. K. (Michele K.), Faul, J. D. (Jessica D.), Feenstra, B. (Bjarke), Feitosa, M. (Mary), Foisy, S. (Sylvain), Franke, A. (Andre), Friedlander, Y. (Yechiel), Gasparini, P. (Paolo), Gieger, C. (Christian), Gonzalez, C. (Clicerio), Goyette, P. (Philippe), Grant, S. F. (Struan F. A.), Griffiths, L. R. (Lyn R.), Groop, L. (Leif), Gudnason, V. (Vilmundur), Gyllensten, U. (Ulf), Hakonarson, H. (Hakon), Hamsten, A. (Anders), van der Harst, P. (Pim), Heng, C.-K. (Chew-Kiat), Hicks, A. A. (Andrew A.), Hochner, H. (Hagit), Huikuri, H. (Heikki), Hunt, S. C. (Steven C.), Jaddoe, V. W. (Vincent W. V.), De Jager, P. L. (Philip L.), Johannesson, M. (Magnus), Johansson, A. (Asa), Jonas, J. B. (Jost B.), Jukema, J. W. (J. Wouter), Junttila, J. (Juhani), Kaprio, J. (Jaakko), Kardia, S. L. (Sharon L. R.), Karpe, F. (Fredrik), Kumari, M. (Meena), Laakso, M. (Markku), van der Laan, S. W. (Sander W.), Lahti, J. (Jari), Laudes, M. (Matthias), Lea, R. A. (Rodney A.), Lieb, W. (Wolfgang), Lumley, T. (Thomas), Martin, N. G. (Nicholas G.), Marz, W. (Winfried), Matullo, G. (Giuseppe), McCarthy, M. I. (Mark I.), Medland, S. E. (Sarah E.), Merriman, T. R. (Tony R.), Metspalu, A. (Andres), Meyer, B. F. (Brian F.), Mohlke, K. L. (Karen L.), Montgomery, G. W. (Grant W.), Mook-Kanamori, D. (Dennis), Munroe, P. B. (Patricia B.), North, K. E. (Kari E.), Nyholt, D. R. (Dale R.), O'connell, J. R. (Jeffery R.), Ober, C. (Carole), Oldehinkel, A. J. (Albertine J.), Palmas, W. (Walter), Palmer, C. (Colin), Pasterkamp, G. G. (Gerard G.), Patin, E. (Etienne), Pennell, C. E. (Craig E.), Perusse, L. (Louis), Peyser, P. A. (Patricia A.), Pirastu, M. (Mario), Polderman, T. J. (Tinca J. C.), Porteous, D. J. (David J.), Posthuma, D. (Danielle), Psaty, B. M. (Bruce M.), Rioux, J. D. (John D.), Rivadeneira, F. (Fernando), Rotimi, C. (Charles), Rotter, J. I. (Jerome I.), Rudan, I. (Igor), Den Ruijter, H. M. (Hester M.), Sanghera, D. K. (Dharambir K.), Sattar, N. (Naveed), Schmidt, R. (Reinhold), Schulze, M. B. (Matthias B.), Schunkert, H. (Heribert), Scott, R. A. (Robert A.), Shuldiner, A. R. (Alan R.), Sim, X. (Xueling), Small, N. (Neil), Smith, J. A. (Jennifer A.), Sotoodehnia, N. (Nona), Tai, E.-S. (E-Shyong), Teumer, A. (Alexander), Timpson, N. J. (Nicholas J.), Toniolo, D. (Daniela), Tregouet, D.-A. (David-Alexandre), Tuomi, T. (Tiinamaija), Vollenweider, P. (Peter), Wang, C. A. (Carol A.), Weir, D. R. (David R.), Whitfield, J. B. (John B.), Wijmenga, C. (Cisca), Wong, T.-Y. (Tien-Yin), Wright, J. (John), Yang, J. (Jingyun), Yu, L. (Lei), Zemel, B. S. (Babette S.), Zonderman, A. B. (Alan B.), Perola, M. (Markus), Magnusson, P. K. (Patrik K. E.), Uitterlinden, A. G. (Andre G.), Kooner, J. S. (Jaspal S.), Chasman, D. I. (Daniel I.), Loos, R. J. (Ruth J. F.), Franceschini, N. (Nora), Franke, L. (Lude), Haley, C. S. (Chris S.), Hayward, C. (Caroline), Walters, R. G. (Robin G.), Perry, J. R. (John R. B.), Esko, T. (Tonu), Helgason, A. (Agnar), Stefansson, K. (Kari), Joshi, P. K. (Peter K.), Kubo, M. (Michiaki), and Wilson, J. F. (James F.)

Abstract

In many species, the offspring of related parents suffer reduced reproductive success, a phenomenon known as inbreeding depression. In humans, the importance of this effect has remained unclear, partly because reproduction between close relatives is both rare and frequently associated with confounding social factors. Here, using genomic inbreeding coefficients (FROH) for >1.4 million individuals, we show that FROH is significantly associated (p < 0.0005) with apparently deleterious changes in 32 out of 100 traits analysed. These changes are associated with runs of homozygosity (ROH), but not with common variant homozygosity, suggesting that genetic variants associated with inbreeding depression are predominantly rare. The effect on fertility is striking: FROH equivalent to the offspring of first cousins is associated with a 55% decrease [95% CI 44–66%] in the odds of having children. Finally, the effects of FROH are confirmed within full-sibling pairs, where the variation in FROH is independent of all environmental confounding.

Published
2019

28. Effect of Iron Levels on Women After Premature or Early-Onset Menopause-Reply

Author

Muka, T, Chowdhury, R, Franco, OH, Chowdhury, Rajiv [0000-0003-4881-5690], and Apollo - University of Cambridge Repository

Subjects
Iron, Menopause, Premature, Humans, Female, Menopause
Abstract

Our study showed that the early onset of menopause is associated with an increased risk of cardiovascular disease and mortality. We agree with Hayes et al as well as Mascitelli and Goldstein that elevated iron levels observed after menopause can be a potential mechanism linking the early onset of menopause with adverse cardiometabolic health. Iron is one of the most abundant metals in the human body and is required as an essential cofactor in many important biological processes, such as oxygen transport, DNA synthesis, energy production, and regulation of cell growth and differentiation.

Published
2018
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30. The role of epigenetic modifications in neurodevelopmental disorders

Author

Dall'Aglio, L. (Lorenza), Muka, T. (Taulant), Cecil, C.A.M. (Charlotte), Bramer, W.M. (Wichor), Verbiest, M.M.P.J. (Michael), Nano, J. (Jana), Hidalgo, A.C. (Andrea Cortes), Franco, O.H. (Oscar), Tiemeier, H.W. (Henning), Dall'Aglio, L. (Lorenza), Muka, T. (Taulant), Cecil, C.A.M. (Charlotte), Bramer, W.M. (Wichor), Verbiest, M.M.P.J. (Michael), Nano, J. (Jana), Hidalgo, A.C. (Andrea Cortes), Franco, O.H. (Oscar), and Tiemeier, H.W. (Henning)

Abstract

Epigenetic processes have been suggested as key mechanisms in the etiology of neurodevelopmental disorders. This systematic review summarizes the current evidence for an association between epigenetics and Autism Spectrum Disorder (ASD) and Attention/Deficit-Hyperactivity Disorder (ADHD). Six databases were searched until the 24th of October 2017. Of the 2169 retrieved articles, 29 met our inclusion criteria. While generally associations between epigenetics and neurodevelopmental disorders were reported, only a few findings were consistent across independent analyses. Differential epigenetic markers were repeatedly identified in OR2L13, C11orf21/TSPAN32, PRRT1 and H3K27 for autism, and in VIPR2 for ADHD. Overall, evidence of an association between epigenetic modifications and ASD or ADHD should be considered preliminary and based on studies suffering from numerous caveats. We highlight the need for carefully designed investigations and for greater homogeneity and provide specific recommendations for future research. Despite the current limited understanding, the suggestive findings and rapid advances in the field hold the promise of a forthcoming elucidation of the role of epigenetic modifications in neurodevelopmental disorders.

Published
2018
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31. Association of maternal prenatal smoking GFI1-locus and cardio-metabolic phenotypes in 18,212 adults

Author

Parmar, P. (Priyanka), Lowry, E. (Estelle), Cugliari, G. (Giovanni), Suderman, M.J. (Matthew J.), Wilson, R. (Rory), Karhunen, V. (Ville), Andrew, T. (Toby), Wiklund, P. (Petri), Wielscher, M. (Matthias), Guarrera, S. (Simonetta), Teumer, A. (Alexander), Lehne, B. (Benjamin), Milani, L. (Lili), de Klein, N. (Niek), Mishra, P.P. (Pashupati P.), Melton, P.E. (Phillip E.), Mandaviya, P.R. (Pooja), Kasela, S. (Silva), Nano, J. (Jana), Zhang, W. (Weihua), Zhang, Y. (Yan), Uitterlinden, A.G. (André), Peters, A. (Annette), Schöttker, B. (Ben), Gieger, C. (Christian), Anderson, D. (Denise), Boomsma, D.I. (Dorret I.), Grabe, H.J. (Hans Jörgen), Panico, S. (Salvatore), Veldink, J.H. (Jan), Meurs, J.B.J. (Joyce) van, Berg, L.H. (Leonard) van den, Beilin, L.J. (Lawrence), Franke, L. (Lude), Loh, M. (Marie), Greevenbroek, M.M. van, Nauck, M. (Matthias), Kähönen, M. (Mika), Hurme, M. (Mikko), Raitakari, O. (Olli), Franco, O.H. (Oscar), Slagboom, P.E. (Eline), van der Harst, P. (Pim), Kunze, S. (Sonja), Felix, S.B. (Stephan), Zhang, T. (Tao), Chen, W. (Wei), Mori, T.A. (Trevor A.), Bonnefond, A. (Amélie), Heijmans, B.T. (Bastiaan T.), Muka, T. (Taulant), Kooner, J.S. (Jaspal S.), Fischer, K. (Krista), Waldenberger, M. (Melanie), Froguel, P. (Philippe), Huang, R.-C. (Rae-Chi), Lehtimäki, T. (Terho), Rathmann, W. (Wolfgang), Relton, C.L. (Caroline), Matullo, G., Brenner, H. (Hermann), Verweij, N. (Niek), Li, S. (Shengxu), Chambers, J.C. (John C.), Järvelin, M.-R. (Marjo-Riitta), Sebert, S. (Sylvain), Parmar, P. (Priyanka), Lowry, E. (Estelle), Cugliari, G. (Giovanni), Suderman, M.J. (Matthew J.), Wilson, R. (Rory), Karhunen, V. (Ville), Andrew, T. (Toby), Wiklund, P. (Petri), Wielscher, M. (Matthias), Guarrera, S. (Simonetta), Teumer, A. (Alexander), Lehne, B. (Benjamin), Milani, L. (Lili), de Klein, N. (Niek), Mishra, P.P. (Pashupati P.), Melton, P.E. (Phillip E.), Mandaviya, P.R. (Pooja), Kasela, S. (Silva), Nano, J. (Jana), Zhang, W. (Weihua), Zhang, Y. (Yan), Uitterlinden, A.G. (André), Peters, A. (Annette), Schöttker, B. (Ben), Gieger, C. (Christian), Anderson, D. (Denise), Boomsma, D.I. (Dorret I.), Grabe, H.J. (Hans Jörgen), Panico, S. (Salvatore), Veldink, J.H. (Jan), Meurs, J.B.J. (Joyce) van, Berg, L.H. (Leonard) van den, Beilin, L.J. (Lawrence), Franke, L. (Lude), Loh, M. (Marie), Greevenbroek, M.M. van, Nauck, M. (Matthias), Kähönen, M. (Mika), Hurme, M. (Mikko), Raitakari, O. (Olli), Franco, O.H. (Oscar), Slagboom, P.E. (Eline), van der Harst, P. (Pim), Kunze, S. (Sonja), Felix, S.B. (Stephan), Zhang, T. (Tao), Chen, W. (Wei), Mori, T.A. (Trevor A.), Bonnefond, A. (Amélie), Heijmans, B.T. (Bastiaan T.), Muka, T. (Taulant), Kooner, J.S. (Jaspal S.), Fischer, K. (Krista), Waldenberger, M. (Melanie), Froguel, P. (Philippe), Huang, R.-C. (Rae-Chi), Lehtimäki, T. (Terho), Rathmann, W. (Wolfgang), Relton, C.L. (Caroline), Matullo, G., Brenner, H. (Hermann), Verweij, N. (Niek), Li, S. (Shengxu), Chambers, J.C. (John C.), Järvelin, M.-R. (Marjo-Riitta), and Sebert, S. (Sylvain)

Abstract

Background: DNA methylation at the GFI1-locus has been repeatedly associated with exposure to smoking from the foetal period onwards. We explored whether DNA methylation may be a mechanism that links exposure to maternal prenatal smoking with offspring's adult cardio-metabolic health. Methods: We meta-analysed the association between DNA methylation at GFI1-locus with maternal prenatal smoking, adult own smoking, and cardio-metabolic phenotypes in 22 population-based studies from Europe, Australia, and USA (n = 18,212). DNA methylation at the GFI1-locus was measured in whole-blood. Multivariable regression models were fitted to examine its association with exposure to prenatal and own adult smoking. DNA methylation levels were analysed in relation to body mass index (BMI), waist circumference (WC), fasting glucose (FG), high-density lipoprotein cholesterol (HDL—C), triglycerides (TG), diastolic, and systolic blood pressure (BP). Findings: Lower DNA methylation at three out of eight GFI1-CpGs was associated with exposure to maternal prenatal smoking, whereas, all eight CpGs were associated with adult own smoking. Lower DNA methylation at cg14179389, the strongest maternal prenatal smoking locus, was associated with increased WC and BP when adjusted for sex, age, and adult smoking with Bonferroni-corrected P < 0·012. In contrast, lower DNA methylation at cg09935388, the strongest adult own smoking locus, was associated with decreased BMI, WC, and BP (adjusted 1 × 10−7 < P < 0.01). Similarly, lower DNA methylation at cg12876356, cg18316974, cg09662411, and cg18146737 was associated with decreased BMI and WC (5 × 10−8 < P < 0.001). Lower DNA methylation at all the CpGs was consistently associated with higher TG levels. Interpretation: Epigenetic changes at the GFI1 were linked to smoking exposure in-utero/in-adulthood and robustly associated with cardio-metabolic risk factors. Fund: European Union's Horizon 2020 research and innovation programme under grant agreement no

Published
2018
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33. Association between progestin-only contraceptive use and cardiometabolic outcomes: A systematic review and meta-analysis

Author

Glisic, M. (Marija), Shahzad, S. (Sara), Tsoli, S. (Stergiani), Chadni, M. (Mahmuda), Asllanaj, E. (Eralda), Rojas, L.Z. (Lyda), Brown, E. (Elizabeth), Chowdhury, R. (Rajiv), Muka, T. (Taulant), Franco, O.H. (Oscar), Glisic, M. (Marija), Shahzad, S. (Sara), Tsoli, S. (Stergiani), Chadni, M. (Mahmuda), Asllanaj, E. (Eralda), Rojas, L.Z. (Lyda), Brown, E. (Elizabeth), Chowdhury, R. (Rajiv), Muka, T. (Taulant), and Franco, O.H. (Oscar)

Abstract

Aims: The association between progestin-only contraceptive (POC) use and the risk of various cardiometabolic outcomes has rarely been studied. We performed a systematic review and meta-analysis to determine the impact of POC use on cardiometabolic outcomes including venous thromboembolism, myocardial infarction, stroke, hypertension and diabetes. Methods and results: Nineteen observational studies (seven cohort and 12 case–control) were included in this systematic review. Of those, nine studies reported the risk of venous thromboembolism, six reported the risk of myocardial infarction, six reported the risk of stroke, three reported the risk of hypertension and two studies reported the risk of developing diabetes with POC use. The pooled adjusted relative risks (RRs) for venous thromboembolism, myocardial infarction and stroke for oral POC users versus non-users based on the random effects model were 1.06 (95% confidence interval (CI) 0.70–1.62), 0.98 (95% CI 0.66–1.47) and 1.02 (95% CI 0.72–1.44), respectively. Stratified analysis by route of administration showed that injectable POC with a RR of 2.62 (95% CI 1.74–3.94), but not oral POCs (RR 1.06, 95% CI 0.7–1.62), was associated with an increased risk of venous thromboembolism. A decreased risk of venous thromboembolism in a subgroup of women using an intrauterine levonorgestrel device was observed with a RR of 0.53 (95% CI 0.32–0.89). No effect of POC use on blood pressure was found, but there was an indication for an increased risk of diabetes with injectable POCs, albeit non-significant. Conclusions: This systematic review and meta-analysis suggests that oral POC use is not associated with an increased risk of developing various cardiometabolic outcomes, whereas injectable POC use might increase the risk of venous thromboembolism.

Published
2018
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34. Electrocardiographic abnormalities in Chagas disease in the general population

Author

Rojas, L.Z. (Lyda), Glisic, M. (Marija), Pletsch-Borba, L. (Laura), Echeverría, L.E. (Luis E.), Bramer, W.M. (Wichor), Bano, A. (Arjola), Stringa, N. (Najada), Zaciragic, A. (Asija), Kraja, B. (Bledar), Asllanaj, E. (Eralda), Chowdhury, R. (Rajiv), Morillo, C.A. (Carlos), Rueda-Ochoa, O.L. (Oscar), Franco, O.H. (Oscar), Muka, T. (Taulant), Rojas, L.Z. (Lyda), Glisic, M. (Marija), Pletsch-Borba, L. (Laura), Echeverría, L.E. (Luis E.), Bramer, W.M. (Wichor), Bano, A. (Arjola), Stringa, N. (Najada), Zaciragic, A. (Asija), Kraja, B. (Bledar), Asllanaj, E. (Eralda), Chowdhury, R. (Rajiv), Morillo, C.A. (Carlos), Rueda-Ochoa, O.L. (Oscar), Franco, O.H. (Oscar), and Muka, T. (Taulant)

Abstract

Background: Chagas disease (CD) is a major public health concern in Latin America and a potentially serious emerging threat in non-endemic countries. Although the association between CD and cardiac abnormalities is widely reported, study design diversity, sample size and quality challenge the information, calling for its update and synthesis, which would be very useful and relevant for physicians in non-endemic countries where health care implications of CD are real and neglected. We performed to systematically review and meta-analyze population-based studies that compared prevalence of overall and specific ECG abnormalities between CD and non-CD participants in the general population. Methods: Six databases (EMBASE, Ovid Medline, Web of Science, Cochrane Central, Google Scholar and Lilacs) were searched systematically. Observational studies were included. Odds ratios (OR) were computed using random-effects model. Results: Forty-nine studies were selected, including 34,023(12,276 CD and 21,747 non-CD). Prevalence of overall ECG abnormalities was higher in participants with CD (40.1%; 95%CIs=39.2-41.0) compared to non-CD (24.1%; 95%CIs=23.5-24.7) (OR=2.78; 95%CIs=2.37-3.26). Among specific ECG abnormalities, prevalence of complete right bundle branch block (RBBB) (OR=4.60; 95%CIs=2.97-7.11), left anterior fascicular block (LAFB) (OR=1.60; 95%CIs=1.21-2.13), combination of complete RBBB/LAFB (OR=3.34; 95%CIs=1.76-6.35), first-degree atrioventricular block (A-V B) (OR=1.71; 95%CIs=1.25-2.33), atrial fibrillation (AF) or flutter (OR=2.11; 95%CIs=1.40-3.19) and ventricular extrasystoles (VE) (OR=1.62; 95%CIs=1.14-2.30) was higher in CD compared to non-CD participants. Conclusions: This systematic review and meta-analysis provides an update and synthesis in this field. This research of observational studies indicates a significant excess in prevalence of ECG abnormalities (40.1%) related to T. cruzi infection in the general population from Chagas endemic regions, being th

Published
2018
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37. Relation of antioxidant capacity of diet and markers of oxidative status with C-reactive protein and adipocytokines: a prospective study

Author

Stringa, N. (Najada), Brahimaj, A. (Adela), Zaciragic, A. (Asija), Dehghan, A. (Abbas), Ikram, M.K. (Kamran), Hofman, A. (Albert), Muka, T. (Taulant), Kiefte-de Jong, J.C. (Jessica), Franco, O.H. (Oscar), Stringa, N. (Najada), Brahimaj, A. (Adela), Zaciragic, A. (Asija), Dehghan, A. (Abbas), Ikram, M.K. (Kamran), Hofman, A. (Albert), Muka, T. (Taulant), Kiefte-de Jong, J.C. (Jessica), and Franco, O.H. (Oscar)

Abstract

_Background_ The role of dietary antioxidants and plasma oxidant-antioxidant status in low-grade chronic inflammation and adipocytokine levels is not established yet. Objectives We aimed to evaluate whether total dietary antioxidant capacity (assessed by dietary ferric reducing antioxidant potential (FRAP)), serum uric acid (UA) and gamma glutamyltransferase (GGT) were associated with low-grade chronic inflammation and circulating adipocytokines. _Methods_ Data of 4506 participants aged ≥ 55 years from the Rotterdam Study were analyzed. Baseline (1990–1993) FRAP score was assessed by a food frequency questionnaire. Baseline UA and GGT levels were assessed in non-fasting serum samples. Serum high sensitivity C-reactive protein (hs-CRP) was measured at baseline and 10 years later. Plasma leptin, adiponectin, plasminogen activator inhibitor-1 (PAI-1) and resistin levels were assessed 10 years later. _Results_ A high FRAP score was associated with lower levels of UA and GGT. Overall, no association was found between FRAP and hs-CRP levels. FRAP score was associated with lower levels of leptin and PAI-1, higher levels of adiponectin, and no difference in resistin levels. Increased levels of UA were associated with higher levels of hs-CRP, PAI-1 and leptin; lower levels of adiponectin and no difference in resistin levels. Similarly, GGT was associated with higher levels of hs-CRP whereas no association was observed between GGT and adipocytokines. _Conclusion_ These findings suggest that overall antioxidant capacity of diet and low levels of UA are associated with circulating adipocytokines whereas no consistent association was found with hs-CRP.

Published
2017
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38. Epigenome-Wide Association Study Identifies Methylation Sites Associated With Liver Enzymes and Hepatic Steatosis

Author

Nano, J. (Jana), Ghanbari, M. (Mohsen), Wang, W. (Wenshi), Vries, P.S. (Paul) de, Dhana, K. (Klodian), Muka, T. (Taulant), Uitterlinden, A.G. (André), Meurs, J.B.J. (Joyce) van, Hofman, A. (Albert), Franco, O.H. (Oscar), Pan, Q. (Qiuwei), Darwish Murad, S. (Sarwa), Dehghan, A. (Abbas), Nano, J. (Jana), Ghanbari, M. (Mohsen), Wang, W. (Wenshi), Vries, P.S. (Paul) de, Dhana, K. (Klodian), Muka, T. (Taulant), Uitterlinden, A.G. (André), Meurs, J.B.J. (Joyce) van, Hofman, A. (Albert), Franco, O.H. (Oscar), Pan, Q. (Qiuwei), Darwish Murad, S. (Sarwa), and Dehghan, A. (Abbas)

Abstract

_BACKGROUND & AIMS:_ Epigenetic mechanisms might be involved in the regulation of liver enzyme level. We aimed to identify CpG sites at which DNA methylation levels are associated with blood levels of liver enzymes and hepatic steatosis. _METHODS:_ We conducted an epigenome-wide association study in whole blood for liver enzyme levels, including gamma-glutamyl transferase (GGT), alanine aminotransferase (ALT), and aspartate aminotransferase (AST), among a discovery set of 731 participants of the Rotterdam Study and sought replication in a non-overlapping sample of 719 individuals. Significant DNA methylation changes were further analyzed to evaluate their relation with hepatic steatosis. Expression levels of the top identified gene were measured in 9 human liver cell lines and compared with expression profiles of its potential targets associated with lipid traits. The candidate gene was subsequently knocked down in human hepatoma cells using lentiviral vectors expressing small hairpin RNAs. _RESULTS:_ Eight probes annotated to SLC7A11, SLC1A5, SLC43A1, PHGDH, PSORS1C1, SREBF1, ANKS3 were associated with GGT and 1 probe annotated to SLC7A11 was associated with ALT after Bonferroni correction (1.0 × 10-7). No probe was identified for AST levels. Four probes for GGT levels including cg06690548 (SLC7A11), cg11376147 (SLC43A1), cg22304262 (SLC1A5), and cg14476101 (PHGDH), and 1 for ALT cg06690548 (SLC7A11) were replicated. DNA methylation at SLC7A11 was associated with reduced risk of hepatic steatosis in participants (odds ratio, 0.69; 95% CI= 0.55-0.93; P value: 2.7 × 10-3). In functional experiments, SLC7A11 was highly expressed in human liver cells; its expression is positively correlated with expression of a panel of lipid-associated genes, indicating a role of SLC7A11 in lipid metabolism. _CONCLUSIONS:_ Our results provide new insights into epigenetic mechanisms associated with markers of liver function and hepatic steatosis, laying the groundwork for future diagno

Published
2017
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39. Achieved systolic blood pressure in older people: A systematic review and meta-analysis

Author

Moraes, A.A.I. (Aline A.I.), Baena, C.P. (Cristina P.), Muka, T. (Taulant), Bano, A. (Arjola), Buitrago-Lopez, A. (Adriana), Zazula, A. (Ana), Erbano, B.O. (Bruna O.), Schio, N.A. (Nicolle Amboni), Guedes, M.H. (Murilo H.), Bramer, W.M. (Wichor), Franco, O.H. (Oscar), Faria-Neto, J.R. (José Rocha), Moraes, A.A.I. (Aline A.I.), Baena, C.P. (Cristina P.), Muka, T. (Taulant), Bano, A. (Arjola), Buitrago-Lopez, A. (Adriana), Zazula, A. (Ana), Erbano, B.O. (Bruna O.), Schio, N.A. (Nicolle Amboni), Guedes, M.H. (Murilo H.), Bramer, W.M. (Wichor), Franco, O.H. (Oscar), and Faria-Neto, J.R. (José Rocha)

Abstract

Background: It remains unclear into which level the systolic blood pressure (SBP) should be lowered in order to provide the best cardiovascular protection among older people. Hypertension guidelines recommendation on attaining SBP levels <150 mmHg in this population is currently based on experts' opinion. To clarify this issue, we systematically reviewed and quantified available evidence on the impact of achieving different SBP levels <150 mmHg on various adverse outcomes in subjects aged ≥60 years old receiving antihypertensive drug treatment. Methods: We searched 8 databases to identify randomized controlled trials (RCTs) and post-hoc analyses or subanalyses of RCTs reporting the effects of attaining different SBP levels <150 mmHg on the risk of stroke, acute myocardial infarction, heart failure, cardiovascular mortality and all-cause mortality in participants aged ≥60 years. We performed random-effects meta-analyses stratified by study design. Results: Eleven studies (> 33,600 participants) were included. Compared with attaining SBP levels ≥140 mmHg, levels of 130 to <140 mmHg were not associated with lower risk of outcomes in the meta-analysis of RCTs, whereas there was an associated reduction of cardiovascular mortality (RR 0.72, 95% CI 0.59-0.88) and all-cause mortality (RR 0.86, 95% CI 0.75-0.99) in the meta-analysis of post-hoc analyses or subanalyses of RCTs. Limited and conflicting data were available for the SBP levels of <130 mmHg and 140 to <150 mmHg. Conclusions: Among older people, there is suggestive evidence that achieving SBP levels of 130 to <140 mmHg is associated with lower risks of cardiovascular and all-cause mortality. Future trials are required to confirm these findings and to provide additional evidence regarding the <130 and 140 to <150 mmHg SBP levels.

Published
2017
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40. Age at natural menopause and risk of type 2 diabetes

Author

Muka, T. (Taulant), Asllanaj, E. (Eralda), Avazverdi, N. (Naim), Jaspers, L. (Loes), Stringa, N. (Najada), Milic, J. (Jelena), Ligthart, S. (Symen), Ikram, M.K. (Kamran), Laven, J.S.E. (Joop), Kavousi, M. (Maryam), Dehghan, A. (Abbas), Franco, O.H. (Oscar), Muka, T. (Taulant), Asllanaj, E. (Eralda), Avazverdi, N. (Naim), Jaspers, L. (Loes), Stringa, N. (Najada), Milic, J. (Jelena), Ligthart, S. (Symen), Ikram, M.K. (Kamran), Laven, J.S.E. (Joop), Kavousi, M. (Maryam), Dehghan, A. (Abbas), and Franco, O.H. (Oscar)

Abstract

__Aims/hypothesis__ In this study, we aimed to examine the association between age at natural menopause and risk of type 2 diabetes, and to assess whether this association is independent of potential mediators. __Methods__ We included 3639 postmenopausal women from the prospective, population-based Rotterdam Study. Age at natural menopause was self-reported retrospectively and was treated as a continuous variable and in categories (premature, <40 years; early, 40–44 years; normal, 45–55 years; and late menopause, >55 years [reference]). Type 2 diabetes events were diagnosed on the basis of medical records and glucose measurements from RotterdamStudy visits. HRs and 95%CIs were calculated using Cox proportional hazards models, adjusted for confounding factors; in another model, they were additionally adjusted for potential mediators, including obesity, C-reactive protein, glucose and insulin, as well as for levels of total oestradiol and androgens. __Results__ During a median follow-up of 9.2 years, we identified 348 individuals with incident type 2 diabetes. After adjustment for confounders, HRs for type 2 diabetes were 3.7 (95% CI 1.8, 7.5), 2.4 (95% CI 1.3, 4.3) and 1.60 (95% CI 1.0, 2.8) for women with premature, early and normal menopause, respectively, relative to those with late menopause (ptrend <0.001). The HR for type 2 diabetes per 1 year older at menopause was 0.96 (95% CI 0.94, 0.98). Further adjustment for BMI, glycaemic traits, metabolic risk factors, C-reactive protein, endogenous sex hormone levels or shared genetic factors did not affect this association. __Conclusions/interpretation__ Early onset of natural menopause is an independent marker for type 2 diabetes in postmenopausal women.

Published
2017
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41. Determinants and Predictors of Grief Severity and Persistence: The Rotterdam Study

Author

Milic, J. (Jelena), Muka, T. (Taulant), Ikram, M.K. (Kamran), Franco, O.H. (Oscar), Tiemeier, H.W. (Henning), Milic, J. (Jelena), Muka, T. (Taulant), Ikram, M.K. (Kamran), Franco, O.H. (Oscar), and Tiemeier, H.W. (Henning)

Abstract

Objective: We aimed to explore correlates and predictors of bereavement severity and persistence (triggered by “loss of a loved one”; referent group partner loss) in the Rotterdam cohort. Method: We used linear regression to examine factors associated with grief severity using a cross-sectional analysis and logistic regression to determine prospective associations. Results: Cross-sectionaly, females, child-lost, higher depressive symptoms, lower education, and difficulties in daily activities were independently associated with a higher bereavement severity. Prospectively (6 years; response rate 71%), the baseline value of the grief severity was the single predictor significantly associated with grief persistence. Discussion: Our results suggest that only grief severity is independently associated with grief persistence. Further studies are needed to confirm our

Published
2017
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42. Serum dehydroepiandrosterone levels are associated with lower risk of type 2 diabetes: the Rotterdam Study

Author

Brahimaj, A. (Adela), Muka, T. (Taulant), Kavousi, M. (Maryam), Laven, J.S.E. (Joop), Dehghan, A. (Abbas), Franco, O.H. (Oscar), Brahimaj, A. (Adela), Muka, T. (Taulant), Kavousi, M. (Maryam), Laven, J.S.E. (Joop), Dehghan, A. (Abbas), and Franco, O.H. (Oscar)

Abstract

Aims/hypothesis: Previous literature documents controversial results for the impact of dehydroepiandrosterone (DHEA) in glucose metabolism. We aimed to assess the associations between serum levels of DHEA and its main derivatives DHEA sulphate (DHEAS) and androstenedione, as well as the ratio of DHEAS to DHEA, and risk of type 2 diabetes. Methods: We used data on serum levels of DHEA, DHEAS and androstenedione from 5189 middle-aged and elderly men and women from the prospective population-based Rotterdam Study. Type 2 diabetes was defined as a fasting blood glucose ≥7.0 mmol/l or a non-fasting blood glucose ≥11.1 mmol/l. Results: During a median follow-up of 10.9 years, 643 patients with incident type 2 diabetes were identified. After adjusting for age, sex, cohort, fasting status, fasting glucose and insulin, and BMI, both serum DHEA levels (per 1 unit natural log-transformed, HR 0.76, 95% CI 0.67, 0.87) and serum DHEAS levels (per 1 unit natural log-transformed, HR 0.82, 95% CI 0.73, 0.92) were inversely associated with risk of type 2 diabetes in the total population. Further adjustment for alcohol, smoking, physical activity, prevalent cardiovascular disease, serum total cholesterol, use of lipid-lowering medications, systolic BP, treatment for hypertension, C-reactive protein, oestradiol and testosterone did not substantially affect the association between DHEA and incident type 2 diabetes (per 1 unit natural log-transformed, HR 0.80, 95% CI 0.65, 0.99), but abolished the association between DHEAS and type 2 diabetes. Androstenedione was not associated with risk of type 2 diabetes, nor was DHEAS to DHEA ratio. Conclusions/interpretation: DHEA serum levels might be an independent marker of type 2 diabetes.

Published
2017
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43. Dietary mineral intake and lung cancer risk: the Rotterdam Study

Author

Muka, T. (Taulant), Kraja, B. (Bledar), Ruiter, T.R. (Rikje), Lahousse, L. (Lies), Keyser, C.E. (Catherina Elisabeth) de, Hofman, A. (Albert), Franco, O.H. (Oscar), Brusselle, G.G. (Guy), Stricker, B.H.Ch. (Bruno), Kiefte-de Jong, J.C. (Jessica), Muka, T. (Taulant), Kraja, B. (Bledar), Ruiter, T.R. (Rikje), Lahousse, L. (Lies), Keyser, C.E. (Catherina Elisabeth) de, Hofman, A. (Albert), Franco, O.H. (Oscar), Brusselle, G.G. (Guy), Stricker, B.H.Ch. (Bruno), and Kiefte-de Jong, J.C. (Jessica)

Abstract

Objective: Limited data are available on the role of mineral intake in the development of lung cancer (LC). We investigated whether dietary calcium, copper, iron, magnesium, selenium and zinc intake were associated with LC risk. Methods: We analyzed data from 5435 participants of the Rotterdam Study, a prospective population-based cohort study among subjects aged 55 years and older. At baseline (1990–1993), diet was measured by a validated food frequency questionnaire. LC events were diagnosed on the basis of pathology data and medical records. Hazard ratios (HRs) on LC for energy-adjusted mineral intake were calculated using Cox regression models while adjusting for potential confounders. Results: During a follow-up period of 22 years, we identified 211 incident cases of LC. A higher zinc intake was associated with 42 % reduction in risk of LC (top tertile vs. first tertile: HR 0.58, 95 % CI 0.35; 0.94, P-for trend = 0.039). Similarly, high intake of iron was associated with reduced risk of LC (top tertile vs. first tertile: HR 0.58, 95 % CI 0.37; 0.92, P-for trend = 0.021

Published
2017
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44. P3413Prevalence of cardiac abnormalities in Chagas disease in the general population: a systematic review and meta-analysis

Author

Rojas Sanchez, L.Z., primary, Glisic, M., additional, Pletsch, L., additional, Rueda-Ochoa, O.L., additional, Echeverria, L.E., additional, Bramer, W., additional, Bano, A., additional, Stringa, N., additional, Zaciragic, A., additional, Kraja, B., additional, Asllanaj, E., additional, Franco, O.H., additional, and Muka, T., additional

Published
2017
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48. Association of vasomotor and other menopausal symptoms with risk of cardiovascular disease: A systematic review and meta-analysis

Author

Muka, T. (Taulant), Oliver-Williams, C. (Clare), Colpani, V. (Veronica), Kunutsor, S. (Setor), Chowdhury, S. (Susmita), Chowdhury, R. (Rajiv), Kavousi, M. (Maryam), Franco, O.H. (Oscar), Muka, T. (Taulant), Oliver-Williams, C. (Clare), Colpani, V. (Veronica), Kunutsor, S. (Setor), Chowdhury, S. (Susmita), Chowdhury, R. (Rajiv), Kavousi, M. (Maryam), and Franco, O.H. (Oscar)

Abstract

Importance Vasomotor symptoms (hot flushes and night sweats) and other symptoms, including depression, anxiety and panic attacks, are commonly experienced by menopausal women and have been associated with an unfavourable cardiovascular risk profile. Objective To investigate whether presence of menopausal symptoms is associated with the development of cardiovascular disease (CVD). Methods Five electronic databases (Medline, EMBASE and Web of Science) were search until February 17th, 2015 to identify relevant studies. Observational cohort studies or randomised intervention studies were eligible for inclusion if they followed participants prospectively (at least 1 year of follow-up), and reported relevant estimates on the association of any vasomotor symptoms, or other menopausal symptoms, with risk of CVD, coronary heart disease (CHD), or stroke in perimenopausal, menopausal, or postmenopausal women. Data were extracted by two independent reviewers using a pre-designed data collection form. Separate pooled relative risks (RRs) for age and non-established cardiovascular risk factors (e.g., education, ethnicity) adjusted data and for established cardiovascular risk factors and potential mediators-adjusted data (e.g., smoking, body mass index, and hypertension) were calculated. Results Out of 9,987 initially identified references, ten studies were selected, including 213,976 women with a total of 10,037 cardiovascular disease outcomes. The age and non-established cardiovascular risk factors adjusted RRs) [95% confidence intervals] for development of CHD, Stroke and CVD comparing women with and without any menopausal symptoms were 1.34 [1.13-1.58], 1.30 [0.99-1.70], 1.48 [1.21-1.80] respectively, and the corresponding RRs adjusted for cardiovascular risk factors and potential mediators were 1.18 [1.03-1.35], 1.08 [0.89-1.32], 1.29 [0.98-1.71]. However, these analyses were limited by potential unmeasured confounding and the small number of studies on this topic. Conclusion

Published
2016
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49. The role of epigenetic modifications in cardiovascular disease

Author

Muka, T. (Taulant), Koromani, F. (Fjorda), Portilla-Fernandez, E. (Eliana), O'Connor, A. (Annalouise), Bramer, W.M. (Wichor), Troup, J. (John), Chowdhury, R. (Rajiv), Dehghan, A. (Abbas), Franco, O.H. (Oscar), Muka, T. (Taulant), Koromani, F. (Fjorda), Portilla-Fernandez, E. (Eliana), O'Connor, A. (Annalouise), Bramer, W.M. (Wichor), Troup, J. (John), Chowdhury, R. (Rajiv), Dehghan, A. (Abbas), and Franco, O.H. (Oscar)

Abstract

_Background:_ Epigenetic modifications of the genome, such as DNA methylation and histone modifications, have been reported to play a role in processes underlying cardiovascular disease (CVD), including atherosclerosis, inflammation, hypertension and diabetes. _Methods:_ Eleven databases were searched for studies investigating the association between epigenetic marks (either global, site-specific or genome-wide methylation of DNA and histone modifications) and CVD. _Results:_ Of the 3459 searched references, 31 studies met our inclusion criteria (26 cross-sectional studies and 5 prospective studies). Overall, 12,648 individuals were included, with total of 4037 CVD events. The global DNA methylation assessed at long-interspersed nuclear element (LINE-1) was inversely associated with CVD, independent of established cardiovascular risk factors. Conversely, a higher degree of global DNA methylation measured at Alu repeats or by the LUMA method was associated with the presence of CVD. The studies reported epigenetic regulation of 34 metabolic genes (involved in fetal growth, glucose and lipid metabolism, inflammation, atherosclerosis and oxidative stress) in blood cells to be related with CVD. Among them, 5 loci were validated and methylation at F2RL3 was reported in two large prospective studies to predict cardiovascular disease beyond the traditional risk factors. _Conclusions:_ Current evidence supports an association between genomic DNA methylation and CVD. However, this review highlights important gaps in the existing evidences including lack of large-scale epigenetic investigations

Published
2016
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50. The role of DNA methylation and histone modifications in neurodegenerative diseases: A systematic review

Author

Wen, K.-X. (Ke-Xin), Milic, J. (Jelena), El-Khodor, B. (Bassem), Dhana, K. (Klodian), Nano, J. (Jana), Pulido, T. (Tammy), Kraja, B. (Bledar), Zaciragic, A. (Asija), Bramer, W.M. (Wichor), Troup, J. (John), Chowdhury, R. (Rajiv), Arfam Ikram, M., Dehghan, A. (Abbas), Muka, T. (Taulant), Franco, O.H. (Oscar), Wen, K.-X. (Ke-Xin), Milic, J. (Jelena), El-Khodor, B. (Bassem), Dhana, K. (Klodian), Nano, J. (Jana), Pulido, T. (Tammy), Kraja, B. (Bledar), Zaciragic, A. (Asija), Bramer, W.M. (Wichor), Troup, J. (John), Chowdhury, R. (Rajiv), Arfam Ikram, M., Dehghan, A. (Abbas), Muka, T. (Taulant), and Franco, O.H. (Oscar)

Abstract

Importance Epigenetic modifications of the genome, such as DNA methylation and histone modifications, have been reported to play a role in neurodegenerative diseases (ND) such as Alzheimer's disease (AD) and Parkinson's disease (PD). Objective To systematically review studies investigating epigenetic marks in AD or PD. Methods Eleven bibliographic databases (Embase.com, Medline (Ovid), Web-of-Science, Scopus, PubMed, Cinahl (EBSCOhost), Cochrane Central, ProQuest, Lilacs, Scielo and Google Scholar) were searched until July 11th 2016 to identify relevant articles. We included all randomized controlled trials, cohort, case-control and cross-sectional studies in humans that examined associations between epigenetic marks and ND. Two independent reviewers, with a third reviewer available for disagreements, performed the abstract and full text selection. Data was extracted using a pre-designed data collection form. Results Of 6,927 searched references, 73 unique case-control studies met our inclusion criteria. Overall, 11,453 individuals were included in this systematic review (2,640 AD and 2,368 PD outcomes). There was no consistent association between global DNA methylation pattern and any ND. Studies reported epigenetic regulation of 31 genes (including cell communication, apoptosis, and neurogenesis genes in blood and brain tissue) in relation to AD and PD. Methylation at the BDNF, SORBS3 and APP genes in AD were the most consistently reported associations. Methylation of a-synuclein gene (SNCA) was also found to be associated with PD. Seven studies reported histone protein alterations in AD and PD. Conclusion Many studies have investigated epigenetics and ND. Further research should include larger cohort or longitudinal studies, in order to identify clinically significant epigenetic changes. Identifying relevant epigenetic changes could lead to interventional strategies in ND.

Published
2016
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