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2. Role of Polyunsaturated Fat in Modifying Cardiovascular Risk Associated With Family History of Cardiovascular Disease: Pooled De Novo Results From 15 Observational Studies.

Author

Brouwer, Ingeborg, De Faire, Ulf, Eiriksdottir, Gudny, Ferrucci, Luigi, Forouhi, Nita, Geleijnse, Johanna, Hodge, Allison, Kimura, Hitomi, Laakso, Markku, Risérus, Ulf, van Westing, Anniek, Bandinelli, Stefania, Baylin, Ana, Giles, Graham, Gudnason, Vilmundur, Iso, Hiroyasu, Lemaitre, Rozenn, Ninomiya, Toshiharu, Post, Wendy, Psaty, Bruce, Salonen, Jukka, Schulze, Matthias, Tsai, Michael, Uusitupa, Matti, Wareham, Nicholas, Oh, Seung-Won, Wood, Alexis, Harris, William, Siscovick, David, Mozaffarian, Dariush, Leander, Karin, Laguzzi, Federica, Åkesson, Agneta, Marklund, Matti, Qian, Frank, Gigante, Bruna, Bartz, Traci, Bassett, Julie, Birukov, Anna, Campos, Hannia, Hirakawa, Yoichiro, Imamura, Fumiaki, Jäger, Susanne, Lankinen, Maria, Murphy, Rachel, Senn, Mackenzie, Tanaka, Toshiko, Tintle, Nathan, Virtanen, Jyrki, Yamagishi, Kazumasa, and Allison, Matthew

Subjects
biomarkers, cardiovascular diseases, family medical history, polyunsaturated fatty acids, precision medicine, Animals, Fatty Acids, Omega-3, Cardiovascular Diseases, Risk Factors, Docosahexaenoic Acids, Biomarkers
Abstract

BACKGROUND: It is unknown whether dietary intake of polyunsaturated fatty acids (PUFA) modifies the cardiovascular disease (CVD) risk associated with a family history of CVD. We assessed interactions between biomarkers of low PUFA intake and a family history in relation to long-term CVD risk in a large consortium. METHODS: Blood and tissue PUFA data from 40 885 CVD-free adults were assessed. PUFA levels ≤25th percentile were considered to reflect low intake of linoleic, alpha-linolenic, and eicosapentaenoic/docosahexaenoic acids (EPA/DHA). Family history was defined as having ≥1 first-degree relative who experienced a CVD event. Relative risks with 95% CI of CVD were estimated using Cox regression and meta-analyzed. Interactions were assessed by analyzing product terms and calculating relative excess risk due to interaction. RESULTS: After multivariable adjustments, a significant interaction between low EPA/DHA and family history was observed (product term pooled RR, 1.09 [95% CI, 1.02-1.16]; P=0.01). The pooled relative risk of CVD associated with the combined exposure to low EPA/DHA, and family history was 1.41 (95% CI, 1.30-1.54), whereas it was 1.25 (95% CI, 1.16-1.33) for family history alone and 1.06 (95% CI, 0.98-1.14) for EPA/DHA alone, compared with those with neither exposure. The relative excess risk due to interaction results indicated no interactions. CONCLUSIONS: A significant interaction between biomarkers of low EPA/DHA intake, but not the other PUFA, and a family history was observed. This novel finding might suggest a need to emphasize the benefit of consuming oily fish for individuals with a family history of CVD.

Published
2024

4. Dietary amino acids and risk of stroke subtypes: a prospective analysis of 356,000 participants in seven European countries

Author

Tong, Tammy Y. N., Clarke, Robert, Schmidt, Julie A., Huybrechts, Inge, Noor, Urwah, Forouhi, Nita G., Imamura, Fumiaki, Travis, Ruth C., Weiderpass, Elisabete, Aleksandrova, Krasimira, Dahm, Christina C., van der Schouw, Yvonne T., Overvad, Kim, Kyrø, Cecilie, Tjønneland, Anne, Kaaks, Rudolf, Katzke, Verena, Schiborn, Catarina, Schulze, Matthias B., Mayen-Chacon, Ana-Lucia, Masala, Giovanna, Sieri, Sabina, de Magistris, Maria Santucci, Tumino, Rosario, Sacerdote, Carlotta, Boer, Jolanda M. A., Verschuren, W. M. Monique, Brustad, Magritt, Nøst, Therese Haugdahl, Crous-Bou, Marta, Petrova, Dafina, Amiano, Pilar, Huerta, José María, Moreno-Iribas, Conchi, Engström, Gunnar, Melander, Olle, Johansson, Kristina, Lindvall, Kristina, Aglago, Elom K., Heath, Alicia K., Butterworth, Adam S., Danesh, John, and Key, Timothy J.

Published
2024
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6. Food consumption by degree of food processing and risk of type 2 diabetes mellitus: a prospective cohort analysis of the European Prospective Investigation into Cancer and Nutrition (EPIC)

Author

Dicken, Samuel J., Dahm, Christina C., Ibsen, Daniel B., Olsen, Anja, Tjønneland, Anne, Louati-Hajji, Mariem, Cadeau, Claire, Marques, Chloé, Schulze, Matthias B., Jannasch, Franziska, Baldassari, Ivan, Manfredi, Luca, Santucci de Magistris, Maria, Sánchez, Maria-Jose, Castro-Espin, Carlota, Palacios, Daniel Rodríguez, Amiano, Pilar, Guevara, Marcela, van der Schouw, Yvonne T., Boer, Jolanda M.A., Verschuren, W.M. Monique, Sharp, Stephen J., Forouhi, Nita G., Wareham, Nicholas J., Vamos, Eszter P., Chang, Kiara, Vineis, Paolo, Heath, Alicia K., Gunter, Marc J., Nicolas, Geneviève, Weiderpass, Elisabete, Huybrechts, Inge, and Batterham, Rachel L.

Published
2024
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7. Meat consumption and incident type 2 diabetes: an individual-participant federated meta-analysis of 1·97 million adults with 100 000 incident cases from 31 cohorts in 20 countries

Author

Li, Chunxiao, Bishop, Tom R P, Imamura, Fumiaki, Sharp, Stephen J, Pearce, Matthew, Brage, Soren, Ong, Ken K, Ahsan, Habibul, Bes-Rastrollo, Maira, Beulens, Joline W J, den Braver, Nicole, Byberg, Liisa, Canhada, Scheine, Chen, Zhengming, Chung, Hsin-Fang, Cortés-Valencia, Adrian, Djousse, Luc, Drouin-Chartier, Jean-Philippe, Du, Huaidong, Du, Shufa, Duncan, Bruce B, Gaziano, J Michael, Gordon-Larsen, Penny, Goto, Atsushi, Haghighatdoost, Fahimeh, Härkänen, Tommi, Hashemian, Maryam, Hu, Frank B, Ittermann, Till, Järvinen, Ritva, Kakkoura, Maria G, Neelakantan, Nithya, Knekt, Paul, Lajous, Martin, Li, Yanping, Magliano, Dianna J, Malekzadeh, Reza, Le Marchand, Loic, Marques-Vidal, Pedro, Martinez-Gonzalez, Miguel A, Maskarinec, Gertraud, Mishra, Gita D, Mohammadifard, Noushin, O'Donoghue, Gráinne, O'Gorman, Donal, Popkin, Barry, Poustchi, Hossein, Sarrafzadegan, Nizal, Sawada, Norie, Schmidt, Maria Inês, Shaw, Jonathan E, Soedamah-Muthu, Sabita, Stern, Dalia, Tong, Lin, van Dam, Rob M, Völzke, Henry, Willett, Walter C, Wolk, Alicja, Yu, Canqing, Forouhi, Nita G, and Wareham, Nicholas J

Published
2024
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8. Trans Fatty Acid Biomarkers and Incident Type 2 Diabetes: Pooled Analysis of 12 Prospective Cohort Studies in the Fatty Acids and Outcomes Research Consortium (FORCE).

Author

Lai, Heidi TM, Imamura, Fumiaki, Korat, Andres V Ardisson, Murphy, Rachel A, Tintle, Nathan, Bassett, Julie K, Chen, Jiaying, Kröger, Janine, Chien, Kuo-Liong, Senn, Mackenzie, Wood, Alexis C, Forouhi, Nita G, Schulze, Matthias B, Harris, William S, Vasan, Ramachandran S, Hu, Frank, Giles, Graham G, Hodge, Allison, Djousse, Luc, Brouwer, Ingeborg A, Qian, Frank, Sun, Qi, Wu, Jason HY, Marklund, Matti, Lemaitre, Rozenn N, Siscovick, David S, Fretts, Amanda M, Shadyab, Aladdin H, Manson, JoAnn E, Howard, Barbara V, Robinson, Jennifer G, Wallace, Robert B, Wareham, Nick J, Chen, Yii-Der Ida, Rotter, Jerome I, Tsai, Michael Y, Micha, Renata, and Mozaffarian, Dariush

Subjects
Epidemiology, Biomedical and Clinical Sciences, Health Sciences, Diabetes, Clinical Research, Metabolic and endocrine, Adolescent, Adult, Biomarkers, Cohort Studies, Diabetes Mellitus, Type 2, Fatty Acids, Humans, Outcome Assessment, Health Care, Prospective Studies, Risk Factors, Trans Fatty Acids, Fatty Acids and Outcomes Research Consortium, Medical and Health Sciences, Endocrinology & Metabolism, Biomedical and clinical sciences, Health sciences
Abstract

ObjectiveTrans fatty acids (TFAs) have harmful biologic effects that could increase the risk of type 2 diabetes (T2D), but evidence remains uncertain. We aimed to investigate the prospective associations of TFA biomarkers and T2D by conducting an individual participant-level pooled analysis.Research design and methodsWe included data from an international consortium of 12 prospective cohorts and nested case-control studies from six nations. TFA biomarkers were measured in blood collected between 1990 and 2008 from 25,126 participants aged ≥18 years without prevalent diabetes. Each cohort conducted de novo harmonized analyses using a prespecified protocol, and findings were pooled using inverse-variance weighted meta-analysis. Heterogeneity was explored by prespecified between-study and within-study characteristics.ResultsDuring a mean follow-up of 13.5 years, 2,843 cases of incident T2D were identified. In multivariable-adjusted pooled analyses, no significant associations with T2D were identified for trans/trans-18:2, relative risk (RR) 1.09 (95% CI 0.94-1.25); cis/trans-18:2, 0.89 (0.73-1.07); and trans/cis-18:2, 0.87 (0.73-1.03). Trans-16:1n-9, total trans-18:1, and total trans-18:2 were inversely associated with T2D (RR 0.81 [95% CI 0.67-0.99], 0.86 [0.75-0.99], and 0.84 [0.74-0.96], respectively). Findings were not significantly different according to prespecified sources of potential heterogeneity (each P ≥ 0.1).ConclusionsCirculating individual trans-18:2 TFA biomarkers were not associated with risk of T2D, while trans-16:1n-9, total trans-18:1, and total trans-18:2 were inversely associated. Findings may reflect the influence of mixed TFA sources (industrial vs. natural ruminant), a general decline in TFA exposure due to policy changes during this period, or the relatively limited range of TFA levels.

Published
2022

9. Interaction between plasma phospholipid odd-chain fatty acids and GAD65 autoantibodies on the incidence of adult-onset diabetes: the EPIC-InterAct case–cohort study

Author

Lampousi, Anna-Maria, Carlsson, Sofia, Löfvenborg, Josefin E., Cabrera-Castro, Natalia, Chirlaque, María-Dolores, Fagherazzi, Guy, Franks, Paul W., Hampe, Christiane S., Jakszyn, Paula, Koulman, Albert, Kyrø, Cecilie, Moreno-Iribas, Conchi, Nilsson, Peter M., Panico, Salvatore, Papier, Keren, van der Schouw, Yvonne T., Schulze, Matthias B., Weiderpass, Elisabete, Zamora-Ros, Raul, Forouhi, Nita G., Sharp, Stephen J., Rolandsson, Olov, and Wareham, Nicholas J.

Published
2023
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10. Dietary intake of plant- and animal-derived protein and incident cardiovascular diseases: the pan-European EPIC-CVD case–cohort study

Author

Zheng, Ju-Sheng, Steur, Marinka, Imamura, Fumiaki, Freisling, Heinz, Johnson, Laura, van der Schouw, Yvonne T, Tong, Tammy YN, Weiderpass, Elisabete, Bajracharya, Rashmita, Crous-Bou, Marta, Dahm, Christina C, Heath, Alicia K, Ibsen, Daniel B, Jannasch, Franziska, Katzke, Verena, Masala, Giovanna, Moreno-Iribas, Conchi, Sacerdote, Carlotta, Schulze, Matthias B, Sieri, Sabina, Wareham, Nicholas J, Danesh, John, Butterworth, Adam S, and Forouhi, Nita G

Published
2024
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11. Avances en nutrición de precisión y enfermedades cardiometabólicas

Author

Martínez-González, Miguel A., Planes, Francisco J., Ruiz-Canela, Miguel, Toledo, Estefanía, Estruch, Ramón, Salas-Salvadó, Jordi, Valdés-Más, Rafael, Mena, Pedro, Castañer, Olga, Fitó, Montse, Clish, Clary, Landberg, Rikard, Wittenbecher, Clemens, Liang, Liming, Guasch-Ferré, Marta, Lamuela-Raventós, Rosa M., Wang, Dong D., Forouhi, Nita, Razquin, Cristina, and Hu, Frank B.

Published
2024
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12. Recent advances in precision nutrition and cardiometabolic diseases

Author

Martínez-González, Miguel A., Planes, Francisco J., Ruiz-Canela, Miguel, Toledo, Estefanía, Estruch, Ramón, Salas-Salvadó, Jordi, Valdés-Más, Rafael, Mena, Pedro, Castañer, Olga, Fitó, Montse, Clish, Clary, Landberg, Rikard, Wittenbecher, Clemens, Liang, Liming, Guasch-Ferré, Marta, Lamuela-Raventós, Rosa M., Wang, Dong D., Forouhi, Nita, Razquin, Cristina, and Hu, Frank B.

Published
2024
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13. Estimating dose-response relationships for vitamin D with coronary heart disease, stroke, and all-cause mortality: observational and Mendelian randomisation analyses

Author

Sofianopoulou, Eleni, Kaptoge, Stephen K, Afzal, Shoaib, Jiang, Tao, Gill, Dipender, Gundersen, Thomas E, Bolton, Thomas R, Allara, Elias, Arnold, Matthew G, Mason, Amy M, Chung, Ryan, Pennells, Lisa A M, Shi, Fanchao, Sun, Luanluan, Willeit, Peter, Forouhi, Nita G, Langenberg, Claudia, Sharp, Stephen J, Panico, Salvatore, Engström, Gunnar, Melander, Olle, Tong, Tammy Y N, Perez-Cornago, Aurora, Norberg, Margareta, Johansson, Ingegerd, Katzke, Verena, Srour, Bernard, Sánchez, María José, Redondo-Sánchez, Daniel, Olsen, Anja, Dahm, Christina C, Overvad, Kim, Brustad, Magritt, Skeie, Guri, Moreno-Iribas, Conchi, Onland-Moret, N Charlotte, van der Schouw, Yvonne T, Tsilidis, Konstantinos K, Heath, Alicia K, Agnoli, Claudia, Krogh, Vittorio, de Boer, Ian H, Kobylecki, Camilla Jannie, Çolak, Yunus, Zittermann, Armin, Sundström, Johan, Welsh, Paul, Weiderpass, Elisabete, Aglago, Elom K, Ferrari, Pietro, Clarke, Robert, Boutron, Marie-Christine, Severi, Gianluca, MacDonald, Conor, Providencia, Rui, Masala, Giovanna, Zamora Ros, Raul, Boer, Jolanda, Verschuren, Wm Monique, Cawthon, Peggy, Schierbeck, Louise L, Cooper, Cyrus, Schulze, Matthias B, Bergmann, Manuela M, Hannemann, Anke, Kiechl, Stefan, Brenner, Hermann, van Schoor, Natasja M, Albertorio, Juan R, Sacerdote, Carlotta, Linneberg, Allan, Kårhus, LineL, Huerta, José María, Imaz, Liher, Joergensen, Christel, Ben-Shlomo, Yoav, Lundqvist, Annamari, Gallacher, John, Sattar, Naveed, Wood, Angela M, Wareham, Nicholas J, Nordestgaard, Børge G, Di Angelantonio, Emanuele, Danesh, John, Butterworth, Adam S, and Burgess, Stephen

Published
2024
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17. Sugar-Sweetened Beverage Consumption May Modify Associations Between Genetic Variants in the CHREBP (Carbohydrate Responsive Element Binding Protein) Locus and HDL-C (High-Density Lipoprotein Cholesterol) and Triglyceride Concentrations.

Author

Haslam, Danielle E, Peloso, Gina M, Guirette, Melanie, Imamura, Fumiaki, Bartz, Traci M, Pitsillides, Achilleas N, Wang, Carol A, Li-Gao, Ruifang, Westra, Jason M, Pitkänen, Niina, Young, Kristin L, Graff, Mariaelisa, Wood, Alexis C, Braun, Kim VE, Luan, Jian'an, Kähönen, Mika, Kiefte-de Jong, Jessica C, Ghanbari, Mohsen, Tintle, Nathan, Lemaitre, Rozenn N, Mook-Kanamori, Dennis O, North, Kari, Helminen, Mika, Mossavar-Rahmani, Yasmin, Snetselaar, Linda, Martin, Lisa W, Viikari, Jorma S, Oddy, Wendy H, Pennell, Craig E, Rosendall, Frits R, Ikram, M Arfan, Uitterlinden, Andre G, Psaty, Bruce M, Mozaffarian, Dariush, Rotter, Jerome I, Taylor, Kent D, Lehtimäki, Terho, Raitakari, Olli T, Livingston, Kara A, Voortman, Trudy, Forouhi, Nita G, Wareham, Nick J, de Mutsert, Renée, Rich, Steven S, Manson, JoAnn E, Mora, Samia, Ridker, Paul M, Merino, Jordi, Meigs, James B, Dashti, Hassan S, Chasman, Daniel I, Lichtenstein, Alice H, Smith, Caren E, Dupuis, Josée, Herman, Mark A, and McKeown, Nicola M

Subjects
Humans, Triglycerides, Polymorphism, Single Nucleotide, Adult, Middle Aged, Female, Male, Basic Helix-Loop-Helix Leucine Zipper Transcription Factors, Cholesterol, HDL, Meta-Analysis as Topic, Sugar-Sweetened Beverages, carbohydrates, dyslipidemia, epidemiology, genetics, nutrition, sugars, triglyceride, Cardiovascular, Genetics, Human Genome
Abstract

BackgroundChREBP (carbohydrate responsive element binding protein) is a transcription factor that responds to sugar consumption. Sugar-sweetened beverage (SSB) consumption and genetic variants in the CHREBP locus have separately been linked to HDL-C (high-density lipoprotein cholesterol) and triglyceride concentrations. We hypothesized that SSB consumption would modify the association between genetic variants in the CHREBP locus and dyslipidemia.MethodsData from 11 cohorts from the Cohorts for Heart and Aging Research in Genomic Epidemiology consortium (N=63 599) and the UK Biobank (N=59 220) were used to quantify associations of SSB consumption, genetic variants, and their interaction on HDL-C and triglyceride concentrations using linear regression models. A total of 1606 single nucleotide polymorphisms within or near CHREBP were considered. SSB consumption was estimated from validated questionnaires, and participants were grouped by their estimated intake.ResultsIn a meta-analysis, rs71556729 was significantly associated with higher HDL-C concentrations only among the highest SSB consumers (β, 2.12 [95% CI, 1.16-3.07] mg/dL per allele; P

Published
2021

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

Author

Meddens, S Fleur W, de Vlaming, Ronald, Bowers, Peter, Burik, Casper AP, Linnér, Richard Karlsson, Lee, Chanwook, Okbay, Aysu, Turley, Patrick, Rietveld, Cornelius A, Fontana, Mark Alan, Ghanbari, Mohsen, Imamura, Fumiaki, McMahon, George, van der Most, Peter J, Voortman, Trudy, Wade, Kaitlin H, Anderson, Emma L, Braun, Kim VE, Emmett, Pauline M, Esko, Tonũ, Gonzalez, Juan R, Kiefte-de Jong, Jessica C, Langenberg, Claudia, Luan, Jian’an, Muka, Taulant, Ring, Susan, Rivadeneira, Fernando, Snieder, Harold, van Rooij, Frank JA, Wolffenbuttel, Bruce HR, Smith, George Davey, Franco, Oscar H, Forouhi, Nita G, Ikram, M Arfan, Uitterlinden, Andre G, van Vliet-Ostaptchouk, Jana V, Wareham, Nick J, Cesarini, David, Harden, K Paige, Lee, James J, Benjamin, Daniel J, Chow, Carson C, and Koellinger, Philipp D

Subjects
Biomedical and Clinical Sciences, Nutrition and Dietetics, Prevention, Behavioral and Social Science, Genetics, Obesity, Human Genome, Nutrition, Diabetes, Aetiology, 2.1 Biological and endogenous factors, Cardiovascular, Metabolic and endocrine, Body Mass Index, Diabetes Mellitus, Type 2, Diet, Genome-Wide Association Study, Genomics, Humans, Life Style, 23andMe Research Team, EPIC- InterAct Consortium, Lifelines Cohort Study, Biological Sciences, Medical and Health Sciences, Psychology and Cognitive Sciences, Psychiatry, Clinical sciences, Biological psychology, Clinical and health psychology
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

Published
2021

19. Role of Polyunsaturated Fat in Modifying Cardiovascular Risk Associated With Family History of Cardiovascular Disease: Pooled De Novo Results From 15 Observational Studies

Author

Laguzzi, Federica, Åkesson, Agneta, Marklund, Matti, Qian, Frank, Gigante, Bruna, Bartz, Traci M., Bassett, Julie K., Birukov, Anna, Campos, Hannia, Hirakawa, Yoichiro, Imamura, Fumiaki, Jäger, Susanne, Lankinen, Maria, Murphy, Rachel A., Senn, Mackenzie, Tanaka, Toshiko, Tintle, Nathan, Virtanen, Jyrki K., Yamagishi, Kazumasa, Allison, Matthew, Brouwer, Ingeborg A., De Faire, Ulf, Eiriksdottir, Gudny., Ferrucci, Luigi, Forouhi, Nita G., Geleijnse, Johanna M., Hodge, Allison M, Kimura, Hitomi, Laakso, Markku, Risérus, Ulf, van Westing, Anniek C., Bandinelli, Stefania, Baylin, Ana, Giles, Graham G., Gudnason, Vilmundur, Iso, Hiroyasu, Lemaitre, Rozenn N., Ninomiya, Toshiharu, Post, Wendy S., Psaty, Bruce M., Salonen, Jukka T., Schulze, Matthias B., Tsai, Michael Y., Uusitupa, Matti, Wareham, Nicholas J., Oh, Seung-Won, Wood, Alexis C., Harris, William S., Siscovick, David, Mozaffarian, Dariush, and Leander, Karin

Published
2024
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20. Omega-3 Blood Levels and Stroke Risk: A Pooled and Harmonized Analysis of 183 291 Participants From 29 Prospective Studies

Author

O’Keefe, James H., Tintle, Nathan L., Harris, William S., O’Keefe, Evan L., Sala-Vila, Aleix, Attia, John, Garg, G. Manohar, Hure, Alexis, Bork, Christian Sørensen, Schmidt, Erik Berg, Venø, Stine Krogh, Chien, Kuo-Liong, Chen, Yun-Yu (Amelia), Egert, Sarah, Feldreich, Tobias Rudholm, Ärnlöv, Johan, Lind, Lars, Forouhi, Nita G., Geleijnse, Johanna M., Pertiwi, Kamalita, Imamura, Fumiaki, de Mello Laaksonen, Vanessa, Uusitupa, W. Matti, Tuomilehto, Jaakko, Laakso, Markku, Lankinen, Maria Anneli, Laurin, Danielle, Carmichael, Pierre-Hugues, Lindsay, Joan, Leander, Karin, Laguzzi, Federica, Swenson, Brenton R., Longstreth, William T., Manson, JoAnn E., Mora, Samia, Cook, Nancy R., Marklund, Matti, Melo van Lent, Debora, Murphy, Rachel, Gudnason, Vilmundur, Ninomiya, Toshihara, Hirakawa, Yoichiro, Qian, Frank, Sun, Qi, Hu, Frank, Ardisson Korat, Andres V., Risérus, Ulf, Lázaro, Iolanda, Samieri, Cecilia, Le Goff, Mélanie, Helmer, Catherine, Steur, Marinka, Voortman, Trudy, Ikram, M. Kamran, Tanaka, Toshiko, Das, Jayanta K., Ferrucci, Luigi, Bandinelli, Stefania, Tsai, Michael, Guan, Weihua, Garg, Parveen, Verschuren, W.M. Monique, Boer, Jolanda M.A., Biokstra, Anneke, Virtanen, Jyrki, Wagner, Michael, Westra, Jason, Albuisson, Luc, Yamagishi, Kazumasa, Siscovick, David S., Lemaitre, Rozenn N., and Mozaffarian, Dariush

Published
2024
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21. Omega-3 Fatty Acid Biomarkers and Incident Atrial Fibrillation

Author

Qian, Frank, Tintle, Nathan, Jensen, Paul N., Lemaitre, Rozenn N., Imamura, Fumiaki, Feldreich, Tobias Rudholm, Nomura, Sarah Oppeneer, Guan, Weihua, Laguzzi, Federica, Kim, Eunjung, Virtanen, Jyrki K., Steur, Marinka, Bork, Christian S., Hirakawa, Yoichiro, O'Donoghue, Michelle L., Sala-Vila, Aleix, Ardisson Korat, Andres V., Sun, Qi, Rimm, Eric B., Psaty, Bruce M., Heckbert, Susan R., Forouhi, Nita G., Wareham, Nicholas J., Marklund, Matti, Risérus, Ulf, Lind, Lars, Ärnlöv, Johan, Garg, Parveen, Tsai, Michael Y., Pankow, James, Misialek, Jeffrey R., Gigante, Bruna, Leander, Karin, Pester, Julie A., Albert, Christine M., Kavousi, Maryam, Ikram, Arfan, Voortman, Trudy, Schmidt, Erik B., Ninomiya, Toshiharu, Morrow, David A., Bayés-Genís, Antoni, O’Keefe, James H., Ong, Kwok Leung, Wu, Jason H.Y., Mozaffarian, Dariush, Harris, William S., and Siscovick, David S.

Published
2023
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22. Associations between exploratory dietary patterns and incident type 2 diabetes: a federated meta-analysis of individual participant data from 25 cohort studies

Author

Jannasch, Franziska, Dietrich, Stefan, Bishop, Tom R. P., Pearce, Matthew, Fanidi, Anouar, O’Donoghue, Gráinne, O’Gorman, Donal, Marques-Vidal, Pedro, Vollenweider, Peter, Bes-Rastrollo, Maira, Byberg, Liisa, Wolk, Alicja, Hashemian, Maryam, Malekzadeh, Reza, Poustchi, Hossein, Luft, Vivian C., de Matos, Sheila M. Alvim, Kim, Jihye, Kim, Mi Kyung, Kim, Yeonjung, Stern, Dalia, Lajous, Martin, Magliano, Dianna J., Shaw, Jonathan E., Akbaraly, Tasnime, Kivimaki, Mika, Maskarinec, Gertraud, Le Marchand, Loïc, Martínez-González, Miguel Ángel, Soedamah-Muthu, Sabita S., Wareham, Nicholas J., Forouhi, Nita G., and Schulze, Matthias B.

Published
2022
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23. Genome-wide meta-analysis of macronutrient intake of 91,114 European ancestry participants from the cohorts for heart and aging research in genomic epidemiology consortium

Author

Merino, Jordi, Dashti, Hassan S, Li, Sherly X, Sarnowski, Chloé, Justice, Anne E, Graff, Misa, Papoutsakis, Constantina, Smith, Caren E, Dedoussis, George V, Lemaitre, Rozenn N, Wojczynski, Mary K, Männistö, Satu, Ngwa, Julius S, Kho, Minjung, Ahluwalia, Tarunveer S, Pervjakova, Natalia, Houston, Denise K, Bouchard, Claude, Huang, Tao, Orho-Melander, Marju, Frazier-Wood, Alexis C, Mook-Kanamori, Dennis O, Pérusse, Louis, Pennell, Craig E, de Vries, Paul S, Voortman, Trudy, Li, Olivia, Kanoni, Stavroula, Rose, Lynda M, Lehtimäki, Terho, Zhao, Jing Hua, Feitosa, Mary F, Luan, Jian’an, McKeown, Nicola M, Smith, Jennifer A, Hansen, Torben, Eklund, Niina, Nalls, Mike A, Rankinen, Tuomo, Huang, Jinyan, Hernandez, Dena G, Schulz, Christina-Alexandra, Manichaikul, Ani, Li-Gao, Ruifang, Vohl, Marie-Claude, Wang, Carol A, van Rooij, Frank JA, Shin, Jean, Kalafati, Ioanna P, Day, Felix, Ridker, Paul M, Kähönen, Mika, Siscovick, David S, Langenberg, Claudia, Zhao, Wei, Astrup, Arne, Knekt, Paul, Garcia, Melissa, Rao, DC, Qi, Qibin, Ferrucci, Luigi, Ericson, Ulrika, Blangero, John, Hofman, Albert, Pausova, Zdenka, Mikkilä, Vera, Wareham, Nick J, Kardia, Sharon LR, Pedersen, Oluf, Jula, Antti, Curran, Joanne E, Zillikens, M Carola, Viikari, Jorma S, Forouhi, Nita G, Ordovás, José M, Lieske, John C, Rissanen, Harri, Uitterlinden, André G, Raitakari, Olli T, Kiefte-de Jong, Jessica C, Dupuis, Josée, Rotter, Jerome I, North, Kari E, Scott, Robert A, Province, Michael A, Perola, Markus, Cupples, L Adrienne, Turner, Stephen T, Sørensen, Thorkild IA, Salomaa, Veikko, Liu, Yongmei, Sung, Yun J, Qi, Lu, Bandinelli, Stefania, Rich, Stephen S, de Mutsert, Renée, Tremblay, Angelo, Oddy, Wendy H, Franco, Oscar H, and Paus, Tomas

Subjects
Biomedical and Clinical Sciences, Clinical Sciences, Obesity, Human Genome, Genetics, Prevention, Clinical Research, 2.1 Biological and endogenous factors, Aetiology, Cardiovascular, Metabolic and endocrine, Aged, Aging, Alpha-Ketoglutarate-Dependent Dioxygenase FTO, Cohort Studies, Energy Intake, Female, Fibroblast Growth Factors, Genetic Loci, Genetic Predisposition to Disease, Genome-Wide Association Study, Genomics, Genotype, Heart Diseases, Humans, Male, Membrane Proteins, Middle Aged, Nutrients, Polymorphism, Single Nucleotide, Receptors, Retinoic Acid, White People, Biological Sciences, Medical and Health Sciences, Psychology and Cognitive Sciences, Psychiatry, Clinical sciences, Biological psychology, Clinical and health psychology
Abstract

Macronutrient intake, the proportion of calories consumed from carbohydrate, fat, and protein, is an important risk factor for metabolic diseases with significant familial aggregation. Previous studies have identified two genetic loci for macronutrient intake, but incomplete coverage of genetic variation and modest sample sizes have hindered the discovery of additional loci. Here, we expanded the genetic landscape of macronutrient intake, identifying 12 suggestively significant loci (P

Published
2019

24. Associations of takeaway outlets with takeaway food consumption and adiposity: longitudinal analysis of the Fenland cohort.

Author

Hoenink, Jody C., Burgoine, Thomas, Forouhi, Nita G., Monsivais, Pablo, Sharp, Stephen J., Panter, Jenna, and Adams, Jean

Abstract

Objective: This study builds on prior findings that link increased availability of takeaway food outlets in home, workplace, and commuting environments to greater takeaway consumption and adiposity. Using longitudinal data, we examine associations of takeaway availability at baseline with changes in consumption and adiposity between baseline and follow‐up. Methods: We analyzed data from the Fenland Study, with baseline data from 2005 to 2015 and follow‐up from 2015 to 2020. Takeaway outlet availability within 1 mile of participants' home and workplace addresses, based on 2011 local authority data, was assessed. Outcomes included takeaway food consumption (from a food frequency questionnaire) and body fat percentage (measured via dual‐energy x‐ray absorptiometry) at follow‐up. Results: Among 7581 participants (mean [SD] age, 49.3 [7.4] years) with a mean follow‐up of 6.7 years, no positive association was found between takeaway outlet availability at baseline and changes in consumption or body fat percentage. However, among the 12 associations tested, the highest combined home–workplace availability of takeaway outlets, compared with none, was associated with a 0.68 decrease in body fat percentage (95% CI: 0.24–1.12). Conclusions: Although takeaway outlet availability was linked to greater consumption and adiposity at baseline, it did not predict changes over time, underscoring the complexity of dietary behaviors and their relationship with the neighborhood food environment. [ABSTRACT FROM AUTHOR]

Published
2024
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27. Genome-wide association study in 79,366 European-ancestry individuals informs the genetic architecture of 25-hydroxyvitamin D levels

Author

Jiang, Xia, O’Reilly, Paul F, Aschard, Hugues, Hsu, Yi-Hsiang, Richards, J Brent, Dupuis, Josée, Ingelsson, Erik, Karasik, David, Pilz, Stefan, Berry, Diane, Kestenbaum, Bryan, Zheng, Jusheng, Luan, Jianan, Sofianopoulou, Eleni, Streeten, Elizabeth A, Albanes, Demetrius, Lutsey, Pamela L, Yao, Lu, Tang, Weihong, Econs, Michael J, Wallaschofski, Henri, Völzke, Henry, Zhou, Ang, Power, Chris, McCarthy, Mark I, Michos, Erin D, Boerwinkle, Eric, Weinstein, Stephanie J, Freedman, Neal D, Huang, Wen-Yi, Van Schoor, Natasja M, van der Velde, Nathalie, Groot, Lisette CPGM de, Enneman, Anke, Cupples, L Adrienne, Booth, Sarah L, Vasan, Ramachandran S, Liu, Ching-Ti, Zhou, Yanhua, Ripatti, Samuli, Ohlsson, Claes, Vandenput, Liesbeth, Lorentzon, Mattias, Eriksson, Johan G, Shea, M Kyla, Houston, Denise K, Kritchevsky, Stephen B, Liu, Yongmei, Lohman, Kurt K, Ferrucci, Luigi, Peacock, Munro, Gieger, Christian, Beekman, Marian, Slagboom, Eline, Deelen, Joris, Heemst, Diana van, Kleber, Marcus E, März, Winfried, de Boer, Ian H, Wood, Alexis C, Rotter, Jerome I, Rich, Stephen S, Robinson-Cohen, Cassianne, den Heijer, Martin, Jarvelin, Marjo-Riitta, Cavadino, Alana, Joshi, Peter K, Wilson, James F, Hayward, Caroline, Lind, Lars, Michaëlsson, Karl, Trompet, Stella, Zillikens, M Carola, Uitterlinden, Andre G, Rivadeneira, Fernando, Broer, Linda, Zgaga, Lina, Campbell, Harry, Theodoratou, Evropi, Farrington, Susan M, Timofeeva, Maria, Dunlop, Malcolm G, Valdes, Ana M, Tikkanen, Emmi, Lehtimäki, Terho, Lyytikäinen, Leo-Pekka, Kähönen, Mika, Raitakari, Olli T, Mikkilä, Vera, Ikram, M Arfan, Sattar, Naveed, Jukema, J Wouter, Wareham, Nicholas J, Langenberg, Claudia, Forouhi, Nita G, Gundersen, Thomas E, Khaw, Kay-Tee, Butterworth, Adam S, Danesh, John, and Spector, Timothy

Subjects
Epidemiology, Biological Sciences, Health Sciences, Genetics, Human Genome, Clinical Research, 2.1 Biological and endogenous factors, Aetiology, Inflammatory and immune system, Amidohydrolases, Autoimmune Diseases, Cohort Studies, Female, Genome-Wide Association Study, Humans, Male, Polymorphism, Single Nucleotide, Vesicular Transport Proteins, Vitamin D, White People
Abstract

Vitamin D is a steroid hormone precursor that is associated with a range of human traits and diseases. Previous GWAS of serum 25-hydroxyvitamin D concentrations have identified four genome-wide significant loci (GC, NADSYN1/DHCR7, CYP2R1, CYP24A1). In this study, we expand the previous SUNLIGHT Consortium GWAS discovery sample size from 16,125 to 79,366 (all European descent). This larger GWAS yields two additional loci harboring genome-wide significant variants (P = 4.7×10-9 at rs8018720 in SEC23A, and P = 1.9×10-14 at rs10745742 in AMDHD1). The overall estimate of heritability of 25-hydroxyvitamin D serum concentrations attributable to GWAS common SNPs is 7.5%, with statistically significant loci explaining 38% of this total. Further investigation identifies signal enrichment in immune and hematopoietic tissues, and clustering with autoimmune diseases in cell-type-specific analysis. Larger studies are required to identify additional common SNPs, and to explore the role of rare or structural variants and gene-gene interactions in the heritability of circulating 25-hydroxyvitamin D levels.

Published
2018

29. A systematic evaluation of seven different scores representing the EAT–Lancet reference diet and mortality, stroke, and greenhouse gas emissions in three cohorts

Author

Stubbendorff, Anna, primary, Stern, Dalia, additional, Ericson, Ulrika, additional, Sonestedt, Emily, additional, Hallström, Elinor, additional, Borné, Yan, additional, Lajous, Martin, additional, Forouhi, Nita G, additional, Olsen, Anja, additional, Dahm, Christina C, additional, and Ibsen, Daniel B, additional

Published
2024
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30. A nutritional biomarker score of the Mediterranean diet and incident type 2 diabetes: Integrated analysis of data from the MedLey randomised controlled trial and the EPIC-InterAct case-cohort study

Author

Sobiecki, Jakub G., Imamura, Fumiaki, Davis, Courtney R., Sharp, Stephen J., Koulman, Albert, Hodgson, Jonathan M., Guevara, Marcela, Schulze, Matthias B., Zheng, Ju-Sheng, Agnoli, Claudia, Bonet, Catalina, Colorado-Yohar, Sandra M., Fagherazzi, Guy, Franks, Paul W., Gundersen, Thomas E., Jannasch, Franziska, Kaaks, Rudolf, Katzke, Verena, Molina-Montes, Esther, Nilsson, Peter M., Palli, Domenico, Panico, Salvatore, Papier, Keren, Rolandsson, Olov, Sacerdote, Carlotta, Tjønneland, Anne, Tong, Tammy Y. N., van der Schouw, Yvonne T., Danesh, John, Butterworth, Adam S., Riboli, Elio, Murphy, Karen J., Wareham, Nicholas J., and Forouhi, Nita G.

Subjects
Type 2 diabetes -- Diagnosis -- Care and treatment, Biological markers -- Analysis, Biological sciences
Abstract

Background Self-reported adherence to the Mediterranean diet has been modestly inversely associated with incidence of type 2 diabetes (T2D) in cohort studies. There is uncertainty about the validity and magnitude of this association due to subjective reporting of diet. The association has not been evaluated using an objectively measured biomarker of the Mediterranean diet. Methods and findings We derived a biomarker score based on 5 circulating carotenoids and 24 fatty acids that discriminated between the Mediterranean or habitual diet arms of a parallel design, 6-month partial-feeding randomised controlled trial (RCT) conducted between 2013 and 2014, the MedLey trial (128 participants out of 166 randomised). We applied this biomarker score in an observational study, the European Prospective Investigation into Cancer and Nutrition (EPIC)-InterAct case-cohort study, to assess the association of the score with T2D incidence over an average of 9.7 years of follow-up since the baseline (1991 to 1998). We included 22,202 participants, of whom 9,453 were T2D cases, with relevant biomarkers from an original case-cohort of 27,779 participants sampled from a cohort of 340,234 people. As a secondary measure of the Mediterranean diet, we used a score estimated from dietary-self report. Within the trial, the biomarker score discriminated well between the 2 arms; the cross-validated C-statistic was 0.88 (95% confidence interval (CI) 0.82 to 0.94). The score was inversely associated with incident T2D in EPIC-InterAct: the hazard ratio (HR) per standard deviation of the score was 0.71 (95% CI: 0.65 to 0.77) following adjustment for sociodemographic, lifestyle and medical factors, and adiposity. In comparison, the HR per standard deviation of the self-reported Mediterranean diet was 0.90 (95% CI: 0.86 to 0.95). Assuming the score was causally associated with T2D, higher adherence to the Mediterranean diet in Western European adults by 10 percentiles of the score was estimated to reduce the incidence of T2D by 11% (95% CI: 7% to 14%). The study limitations included potential measurement error in nutritional biomarkers, unclear specificity of the biomarker score to the Mediterranean diet, and possible residual confounding. Conclusions These findings suggest that objectively assessed adherence to the Mediterranean diet is associated with lower risk of T2D and that even modestly higher adherence may have the potential to reduce the population burden of T2D meaningfully. Trial registration Australian New Zealand Clinical Trials Registry (ANZCTR) ACTRN12613000602729 https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=363860., Author(s): Jakub G. Sobiecki 1, Fumiaki Imamura 1, Courtney R. Davis 2, Stephen J. Sharp 1, Albert Koulman 1,3, Jonathan M. Hodgson 4,5, Marcela Guevara 6,7,8, Matthias B. Schulze 9,10,11, [...]

Published
2023
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31. Integrative genomic analysis implicates limited peripheral adipose storage capacity in the pathogenesis of human insulin resistance

Author

Lotta, Luca A, Gulati, Pawan, Day, Felix R, Payne, Felicity, Ongen, Halit, van de Bunt, Martijn, Gaulton, Kyle J, Eicher, John D, Sharp, Stephen J, Luan, Jian'an, De Lucia Rolfe, Emanuella, Stewart, Isobel D, Wheeler, Eleanor, Willems, Sara M, Adams, Claire, Yaghootkar, Hanieh, Forouhi, Nita G, Khaw, Kay-Tee, Johnson, Andrew D, Semple, Robert K, Frayling, Timothy, Perry, John RB, Dermitzakis, Emmanouil, McCarthy, Mark I, Barroso, Inês, Wareham, Nicholas J, Savage, David B, Langenberg, Claudia, O'Rahilly, Stephen, and Scott, Robert A

Subjects
Biochemistry and Cell Biology, Biological Sciences, Clinical Research, Human Genome, Genetics, Diabetes, Aetiology, 2.1 Biological and endogenous factors, Metabolic and endocrine, Adipose Tissue, Animals, Blood Glucose, Body Mass Index, Cardiovascular Diseases, Case-Control Studies, Disease Models, Animal, Female, Genome-Wide Association Study, Genomics, Humans, Insulin Resistance, Male, Metabolic Diseases, Mice, Obesity, Phenotype, EPIC-InterAct Consortium, Cambridge FPLD1 Consortium, Medical and Health Sciences, Developmental Biology, Agricultural biotechnology, Bioinformatics and computational biology
Abstract

Insulin resistance is a key mediator of obesity-related cardiometabolic disease, yet the mechanisms underlying this link remain obscure. Using an integrative genomic approach, we identify 53 genomic regions associated with insulin resistance phenotypes (higher fasting insulin levels adjusted for BMI, lower HDL cholesterol levels and higher triglyceride levels) and provide evidence that their link with higher cardiometabolic risk is underpinned by an association with lower adipose mass in peripheral compartments. Using these 53 loci, we show a polygenic contribution to familial partial lipodystrophy type 1, a severe form of insulin resistance, and highlight shared molecular mechanisms in common/mild and rare/severe insulin resistance. Population-level genetic analyses combined with experiments in cellular models implicate CCDC92, DNAH10 and L3MBTL3 as previously unrecognized molecules influencing adipocyte differentiation. Our findings support the notion that limited storage capacity of peripheral adipose tissue is an important etiological component in insulin-resistant cardiometabolic disease and highlight genes and mechanisms underpinning this link.

Published
2017

32. Omega-3 Blood Levels and Stroke Risk : A Pooled and Harmonized Analysis of 183 291 Participants From 29 Prospective Studies

Author

O'Keefe, James H., Tintle, Nathan L., Harris, William S., O'Keefe, Evan L., Sala-Vila, Aleix, Attia, John, Garg, G. Manohar, Hure, Alexis, Sørensen Bork, Christian, Berg Schmidt, Erik, Krogh Venø, Stine, Chien, Kuo-Liong, Chen, Yun-Yu Amelia, Egert, Sarah, Rudholm Feldreich, Tobias, Ärnlöv, Johan, Lind, Lars, Forouhi, Nita G., Geleijnse, Johanna M., Pertiwi, Kamalita, Imamura, Fumiaki, de Mello Laaksonen, Vanessa, Uusitupa, W. Matti, Tuomilehto, Jaakko, Laakso, Markku, Lankinen, Maria Anneli, Laurin, Danielle, Carmichael, Pierre-Hugues, Lindsay, Joan, Leander, Karin, Laguzzi, Federica, Swenson, Brenton R., Longstreth, William T., Manson, JoAnn E., Mora, Samia, Cook, Nancy R., Marklund, Matti, Melo van Lent, Debora, Murphy, Rachel, Gudnason, Vilmundur, Ninomiya, Toshihara, Hirakawa, Yoichiro, Qian, Frank, Sun, Qi, Hu, Frank, Ardisson Korat, Andres V., Risérus, Ulf, Lázaro, Iolanda, Samieri, Cecilia, Le Goff, Mélanie, Helmer, Catherine, Steur, Marinka, Voortman, Trudy, Ikram, M. Kamran, Tanaka, Toshiko, Das, Jayanta K., Ferrucci, Luigi, Bandinelli, Stefania, Tsai, Michael, Guan, Weihua, Garg, Parveen, Verschuren, W. M. Monique, Boer, Jolanda M. A., Biokstra, Anneke, Virtanen, Jyrki, Wagner, Michael, Westra, Jason, Albuisson, Luc, Yamagishi, Kazumasa, Siscovick, David S., Lemaitre, Rozenn N., Mozaffarian, Dariush, O'Keefe, James H., Tintle, Nathan L., Harris, William S., O'Keefe, Evan L., Sala-Vila, Aleix, Attia, John, Garg, G. Manohar, Hure, Alexis, Sørensen Bork, Christian, Berg Schmidt, Erik, Krogh Venø, Stine, Chien, Kuo-Liong, Chen, Yun-Yu Amelia, Egert, Sarah, Rudholm Feldreich, Tobias, Ärnlöv, Johan, Lind, Lars, Forouhi, Nita G., Geleijnse, Johanna M., Pertiwi, Kamalita, Imamura, Fumiaki, de Mello Laaksonen, Vanessa, Uusitupa, W. Matti, Tuomilehto, Jaakko, Laakso, Markku, Lankinen, Maria Anneli, Laurin, Danielle, Carmichael, Pierre-Hugues, Lindsay, Joan, Leander, Karin, Laguzzi, Federica, Swenson, Brenton R., Longstreth, William T., Manson, JoAnn E., Mora, Samia, Cook, Nancy R., Marklund, Matti, Melo van Lent, Debora, Murphy, Rachel, Gudnason, Vilmundur, Ninomiya, Toshihara, Hirakawa, Yoichiro, Qian, Frank, Sun, Qi, Hu, Frank, Ardisson Korat, Andres V., Risérus, Ulf, Lázaro, Iolanda, Samieri, Cecilia, Le Goff, Mélanie, Helmer, Catherine, Steur, Marinka, Voortman, Trudy, Ikram, M. Kamran, Tanaka, Toshiko, Das, Jayanta K., Ferrucci, Luigi, Bandinelli, Stefania, Tsai, Michael, Guan, Weihua, Garg, Parveen, Verschuren, W. M. Monique, Boer, Jolanda M. A., Biokstra, Anneke, Virtanen, Jyrki, Wagner, Michael, Westra, Jason, Albuisson, Luc, Yamagishi, Kazumasa, Siscovick, David S., Lemaitre, Rozenn N., and Mozaffarian, Dariush

Abstract

BACKGROUND: The effect of marine omega-3 PUFAs on risk of stroke remains unclear. METHODS: We investigated the associations between circulating and tissue omega-3 PUFA levels and incident stroke (total, ischemic, and hemorrhagic) in 29 international prospective cohorts. Each site conducted a de novo individual-level analysis using a prespecified analytical protocol with defined exposures, covariates, analytical methods, and outcomes; the harmonized data from the studies were then centrally pooled. Multivariable-adjusted HRs and 95% CIs across omega-3 PUFA quintiles were computed for each stroke outcome. RESULTS: Among 183 291 study participants, there were 10 561 total strokes, 8220 ischemic strokes, and 1142 hemorrhagic strokes recorded over a median of 14.3 years follow-up. For eicosapentaenoic acid, comparing quintile 5 (Q5, highest) with quintile 1 (Q1, lowest), total stroke incidence was 17% lower (HR, 0.83 [CI, 0.76–0.91]; P<0.0001), and ischemic stroke was 18% lower (HR, 0.82 [CI, 0.74–0.91]; P<0.0001). For docosahexaenoic acid, comparing Q5 with Q1, there was a 12% lower incidence of total stroke (HR, 0.88 [CI, 0.81–0.96]; P=0.0001) and a 14% lower incidence of ischemic stroke (HR, 0.86 [CI, 0.78–0.95]; P=0.0001). Neither eicosapentaenoic acid nor docosahexaenoic acid was associated with a risk for hemorrhagic stroke. These associations were not modified by either baseline history of AF or prevalent CVD. CONCLUSIONS: Higher omega-3 PUFA levels are associated with lower risks of total and ischemic stroke but have no association with hemorrhagic stroke.

Published
2024
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33. Plasma concentration of 36 (poly)phenols and prospective body weight change in participants from the EPIC cohort

Author

Gil-Lespinard, Mercedes, Almanza-Aguilera, Enrique, Castañeda, Jazmín, Guiñón-Fort, Daniel, Eriksen, Anne Kirstine, Tjønneland, Anne, Rothwell, Joseph A., Shah, Sanam, Cadeau, Claire, Katzke, Verena, Johnson, Theron, Schulze, Matthias B., Oliverio, Andreina, Pasanisi, Fabrizio, Tumino, Rosario, Manfredi, Luca, Masala, Giovana, Skeie, Guri, Lundblad, Marie Wasmuth, Brustad, Magritt, Lasheras, Cristina, Crous-Bou, Marta, Molina-Montes, Esther, Colorado-Yohar, Sandra, Guevara, Marcela, Amiano, Pilar, Johansson, Ingegerd, Hultdin, Johan, Forouhi, Nita G., Freisling, Heinz, Merdas, Mira, Debras, Charlotte, Heath, Alicia K., Aglago, Elom K., Aune, Dagfinn, Zamora-Ros, Raul, Gil-Lespinard, Mercedes, Almanza-Aguilera, Enrique, Castañeda, Jazmín, Guiñón-Fort, Daniel, Eriksen, Anne Kirstine, Tjønneland, Anne, Rothwell, Joseph A., Shah, Sanam, Cadeau, Claire, Katzke, Verena, Johnson, Theron, Schulze, Matthias B., Oliverio, Andreina, Pasanisi, Fabrizio, Tumino, Rosario, Manfredi, Luca, Masala, Giovana, Skeie, Guri, Lundblad, Marie Wasmuth, Brustad, Magritt, Lasheras, Cristina, Crous-Bou, Marta, Molina-Montes, Esther, Colorado-Yohar, Sandra, Guevara, Marcela, Amiano, Pilar, Johansson, Ingegerd, Hultdin, Johan, Forouhi, Nita G., Freisling, Heinz, Merdas, Mira, Debras, Charlotte, Heath, Alicia K., Aglago, Elom K., Aune, Dagfinn, and Zamora-Ros, Raul

Abstract

Introduction: Dietary intake of (poly)phenols has been linked to reduced adiposity and body weight (BW) in several epidemiological studies. However, epidemiological evidence on (poly)phenol biomarkers, particularly plasma concentrations, is scarce. We aimed to investigate the associations between plasma (poly)phenols and prospective BW change in participants from the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. Methods: This study included 761 participants with data on BW at baseline and after 5 years of follow-up. Plasma concentrations of 36 (poly)phenols were measured at baseline using liquid chromatography-tandem mass spectrometry. Associations were assessed through general linear mixed models and multinomial logistic regression models, using change in BW as a continuous or as a categorical variable (BW loss, maintenance, gain), respectively. Plasma (poly)phenols were assessed as log2-transformed continuous variables. The false discovery rate (FDR) was used to control for multiple comparisons. Results: Doubling plasma (poly)phenol concentrations showed a borderline trend towards a positive association with BW loss. Plasma vanillic acid showed the strongest association (−0.53 kg/5 years; 95% confidence interval [CI]: −0.99, −0.07). Similar results were observed for plasma naringenin comparing BW loss versus BW maintenance (odds ratio: 1.1; 95% CI: 1.0, 1.2). These results did not remain significant after FDR correction. Conclusion: Higher concentrations of plasma (poly)phenols suggested a tendency towards 5-year BW maintenance or loss. While certain associations seemed promising, they did not withstand FDR correction, indicating the need for caution in interpreting these results. Further studies using (poly) phenol biomarkers are needed to confirm these suggestive protective trends.

Published
2024
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34. A systematic evaluation of seven different scores representing the EAT–Lancet reference diet and mortality, stroke, and greenhouse gas emissions in three cohorts

Author

Stubbendorff, Anna, Stern, Dalia, Ericson, Ulrika, Sonestedt, Emily, Hallström, Elinor, Borné, Yan, Lajous, Martin, Forouhi, Nita G, Olsen, Anja, Dahm, Christina C, Ibsen, Daniel B, Stubbendorff, Anna, Stern, Dalia, Ericson, Ulrika, Sonestedt, Emily, Hallström, Elinor, Borné, Yan, Lajous, Martin, Forouhi, Nita G, Olsen, Anja, Dahm, Christina C, and Ibsen, Daniel B

Abstract

Different approaches have been used for translation of the EAT–Lancet reference diet into dietary scores that can be used to assess health and environmental impact. Our aim was to compare the different EAT–Lancet diet scores, and to estimate their associations with all-cause mortality, stroke incidence, and greenhouse gas emissions. We did a systematic review (PROSPERO, CRD42021286597) to identify different scores representing adherence to the EAT–Lancet reference diet. We then qualitatively compared the diet adherence scores, including their ability to group individuals according the EAT–Lancet reference diet recommendations, and quantitatively assessed the associations of the diet scores with health and environmental outcome data in three diverse cohorts: the Danish Diet, Cancer and Health Cohort (DCH; n=52 452), the Swedish Malmö Diet and Cancer Cohort (MDC; n=20 973), and the Mexican Teachers’ Cohort (MTC; n=30 151). The DCH and MTC used food frequency questionnaires and the MDC used a modified diet history method to assess dietary intake, which we used to compute EAT–Lancet diet scores and evaluate the associations of scores with hazard of all-cause mortality and stroke. In the MDC, dietary greenhouse gas emission values were summarised for every participant, which we used to predict greenhouse gas emissions associated with varying diet adherence scores on each scoring system. In our review, seven diet scores were identified (Knuppel et al, 2019; Trijsburg et al, 2020; Cacau et al, 2021; Hanley-Cook et al, 2021; Kesse-Guyot et al, 2021; Stubbendorff et al, 2022; and Colizzi et al, 2023). Two of the seven scores (Stubbendorff and Colizzi) were among the most consistent in grouping participants according to the EAT–Lancet reference diet recommendations across cohorts, and higher scores (greater diet adherence) were associated with decreased risk of mortality (in the DCH and MDC), decreased risk of incident stroke (in the DCH and MDC for the Stubbendorff score; an, DBI was supported by a research grant from the Independent Research Fund Denmark (grant number 1057-00016B). AS was supported by research grants from The Swedish Heart Lung Foundation (grant number 20200482), Crafoord Foundation (grant number 20210674), and Agenda 2030 Graduate School, Lund University. NGF is supported by the MRC Epidemiology Unit (grant number MC_UU_00006/3) and the National Institute for Health and Care Research (NIHR) Cambridge Biomedical Research Centre (grant number NIHR203312), and she is an NIHR Senior Investigator.

Published
2024
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35. Dietary intake of plant- and animal-derived protein and incident cardiovascular diseases: the pan-European EPIC-CVD case–cohort study

Author

Cardiometabolic Health, Circulatory Health, JC onderzoeksprogramma Cardiovasculaire Epidemiologie, Cardiovasculaire Epi Team 1, Zheng, Ju Sheng, Steur, Marinka, Imamura, Fumiaki, Freisling, Heinz, Johnson, Laura, van der Schouw, Yvonne T., Tong, Tammy YN, Weiderpass, Elisabete, Bajracharya, Rashmita, Crous-Bou, Marta, Dahm, Christina C., Heath, Alicia K., Ibsen, Daniel B., Jannasch, Franziska, Katzke, Verena, Masala, Giovanna, Moreno-Iribas, Conchi, Sacerdote, Carlotta, Schulze, Matthias B., Sieri, Sabina, Wareham, Nicholas J., Danesh, John, Butterworth, Adam S., Forouhi, Nita G., Cardiometabolic Health, Circulatory Health, JC onderzoeksprogramma Cardiovasculaire Epidemiologie, Cardiovasculaire Epi Team 1, Zheng, Ju Sheng, Steur, Marinka, Imamura, Fumiaki, Freisling, Heinz, Johnson, Laura, van der Schouw, Yvonne T., Tong, Tammy YN, Weiderpass, Elisabete, Bajracharya, Rashmita, Crous-Bou, Marta, Dahm, Christina C., Heath, Alicia K., Ibsen, Daniel B., Jannasch, Franziska, Katzke, Verena, Masala, Giovanna, Moreno-Iribas, Conchi, Sacerdote, Carlotta, Schulze, Matthias B., Sieri, Sabina, Wareham, Nicholas J., Danesh, John, Butterworth, Adam S., and Forouhi, Nita G.

Published
2024

36. Omega-3 Blood Levels and Stroke Risk: A Pooled and Harmonized Analysis of 183 291 Participants From 29 Prospective Studies

Author

Cardiometabolic Health, Circulatory Health, JC onderzoeksprogramma Cardiovasculaire Epidemiologie, O'Keefe, James H, Tintle, Nathan L, Harris, William S, O'Keefe, Evan L, Sala-Vila, Aleix, Attia, John, Garg, G Manohar, Hure, Alexis, Bork, Christian Sørensen, Schmidt, Erik Berg, Venø, Stine Krogh, Chien, Kuo-Liong, Chen, Yun-Yu Amelia, Egert, Sarah, Feldreich, Tobias Rudholm, Ärnlöv, Johan, Lind, Lars, Forouhi, Nita G, Geleijnse, Johanna M, Pertiwi, Kamalita, Imamura, Fumiaki, de Mello Laaksonen, Vanessa, Uusitupa, W Matti, Tuomilehto, Jaakko, Laakso, Markku, Lankinen, Maria Anneli, Laurin, Danielle, Carmichael, Pierre-Hugues, Lindsay, Joan, Leander, Karin, Laguzzi, Federica, Swenson, Brenton R, Longstreth, William T, Manson, JoAnn E, Mora, Samia, Cook, Nancy R, Marklund, Matti, Melo van Lent, Debora, Murphy, Rachel, Gudnason, Vilmundur, Ninomiya, Toshihara, Hirakawa, Yoichiro, Qian, Frank, Sun, Qi, Hu, Frank, Ardisson Korat, Andres V, Risérus, Ulf, Lázaro, Iolanda, Samieri, Cecilia, Le Goff, Mélanie, Helmer, Catherine, Steur, Marinka, Voortman, Trudy, Ikram, M Kamran, Tanaka, Toshiko, Das, Jayanta K, Ferrucci, Luigi, Bandinelli, Stefania, Tsai, Michael, Guan, Weihua, Garg, Parveen, Verschuren, W M Monique, Boer, Jolanda M A, Biokstra, Anneke, Virtanen, Jyrki, Wagner, Michael, Westra, Jason, Albuisson, Luc, Yamagishi, Kazumasa, Siscovick, David S, Lemaitre, Rozenn N, Mozaffarian, Dariush, Cardiometabolic Health, Circulatory Health, JC onderzoeksprogramma Cardiovasculaire Epidemiologie, O'Keefe, James H, Tintle, Nathan L, Harris, William S, O'Keefe, Evan L, Sala-Vila, Aleix, Attia, John, Garg, G Manohar, Hure, Alexis, Bork, Christian Sørensen, Schmidt, Erik Berg, Venø, Stine Krogh, Chien, Kuo-Liong, Chen, Yun-Yu Amelia, Egert, Sarah, Feldreich, Tobias Rudholm, Ärnlöv, Johan, Lind, Lars, Forouhi, Nita G, Geleijnse, Johanna M, Pertiwi, Kamalita, Imamura, Fumiaki, de Mello Laaksonen, Vanessa, Uusitupa, W Matti, Tuomilehto, Jaakko, Laakso, Markku, Lankinen, Maria Anneli, Laurin, Danielle, Carmichael, Pierre-Hugues, Lindsay, Joan, Leander, Karin, Laguzzi, Federica, Swenson, Brenton R, Longstreth, William T, Manson, JoAnn E, Mora, Samia, Cook, Nancy R, Marklund, Matti, Melo van Lent, Debora, Murphy, Rachel, Gudnason, Vilmundur, Ninomiya, Toshihara, Hirakawa, Yoichiro, Qian, Frank, Sun, Qi, Hu, Frank, Ardisson Korat, Andres V, Risérus, Ulf, Lázaro, Iolanda, Samieri, Cecilia, Le Goff, Mélanie, Helmer, Catherine, Steur, Marinka, Voortman, Trudy, Ikram, M Kamran, Tanaka, Toshiko, Das, Jayanta K, Ferrucci, Luigi, Bandinelli, Stefania, Tsai, Michael, Guan, Weihua, Garg, Parveen, Verschuren, W M Monique, Boer, Jolanda M A, Biokstra, Anneke, Virtanen, Jyrki, Wagner, Michael, Westra, Jason, Albuisson, Luc, Yamagishi, Kazumasa, Siscovick, David S, Lemaitre, Rozenn N, and Mozaffarian, Dariush

Published
2024

37. Dietary amino acids and risk of stroke subtypes: a prospective analysis of 356,000 participants in seven European countries

Author

Cardiovasculaire Epi Team 1, Circulatory Health, JC onderzoeksprogramma Cardiovasculaire Epidemiologie, Cardiometabolic Health, Tong, Tammy Y.N., Clarke, Robert, Schmidt, Julie A., Huybrechts, Inge, Noor, Urwah, Forouhi, Nita G., Imamura, Fumiaki, Travis, Ruth C., Weiderpass, Elisabete, Aleksandrova, Krasimira, Dahm, Christina C., van der Schouw, Yvonne T., Overvad, Kim, Kyrø, Cecilie, Tjønneland, Anne, Kaaks, Rudolf, Katzke, Verena, Schiborn, Catarina, Schulze, Matthias B., Mayen-Chacon, Ana Lucia, Masala, Giovanna, Sieri, Sabina, de Magistris, Maria Santucci, Tumino, Rosario, Sacerdote, Carlotta, Boer, Jolanda M.A., Verschuren, W. M.Monique, Brustad, Magritt, Nøst, Therese Haugdahl, Crous-Bou, Marta, Petrova, Dafina, Amiano, Pilar, Huerta, José María, Moreno-Iribas, Conchi, Engström, Gunnar, Melander, Olle, Johansson, Kristina, Lindvall, Kristina, Aglago, Elom K., Heath, Alicia K., Butterworth, Adam S., Danesh, John, Key, Timothy J., Cardiovasculaire Epi Team 1, Circulatory Health, JC onderzoeksprogramma Cardiovasculaire Epidemiologie, Cardiometabolic Health, Tong, Tammy Y.N., Clarke, Robert, Schmidt, Julie A., Huybrechts, Inge, Noor, Urwah, Forouhi, Nita G., Imamura, Fumiaki, Travis, Ruth C., Weiderpass, Elisabete, Aleksandrova, Krasimira, Dahm, Christina C., van der Schouw, Yvonne T., Overvad, Kim, Kyrø, Cecilie, Tjønneland, Anne, Kaaks, Rudolf, Katzke, Verena, Schiborn, Catarina, Schulze, Matthias B., Mayen-Chacon, Ana Lucia, Masala, Giovanna, Sieri, Sabina, de Magistris, Maria Santucci, Tumino, Rosario, Sacerdote, Carlotta, Boer, Jolanda M.A., Verschuren, W. M.Monique, Brustad, Magritt, Nøst, Therese Haugdahl, Crous-Bou, Marta, Petrova, Dafina, Amiano, Pilar, Huerta, José María, Moreno-Iribas, Conchi, Engström, Gunnar, Melander, Olle, Johansson, Kristina, Lindvall, Kristina, Aglago, Elom K., Heath, Alicia K., Butterworth, Adam S., Danesh, John, and Key, Timothy J.

Published
2024

38. Dietary intake of plant- and animal-derived protein and incident cardiovascular diseases:the pan-European EPIC-CVD case–cohort study

Author

Zheng, Ju Sheng, Steur, Marinka, Imamura, Fumiaki, Freisling, Heinz, Johnson, Laura, van der Schouw, Yvonne T., Tong, Tammy YN, Weiderpass, Elisabete, Bajracharya, Rashmita, Crous-Bou, Marta, Dahm, Christina C., Heath, Alicia K., Ibsen, Daniel B., Jannasch, Franziska, Katzke, Verena, Masala, Giovanna, Moreno-Iribas, Conchi, Sacerdote, Carlotta, Schulze, Matthias B., Sieri, Sabina, Wareham, Nicholas J., Danesh, John, Butterworth, Adam S., Forouhi, Nita G., Zheng, Ju Sheng, Steur, Marinka, Imamura, Fumiaki, Freisling, Heinz, Johnson, Laura, van der Schouw, Yvonne T., Tong, Tammy YN, Weiderpass, Elisabete, Bajracharya, Rashmita, Crous-Bou, Marta, Dahm, Christina C., Heath, Alicia K., Ibsen, Daniel B., Jannasch, Franziska, Katzke, Verena, Masala, Giovanna, Moreno-Iribas, Conchi, Sacerdote, Carlotta, Schulze, Matthias B., Sieri, Sabina, Wareham, Nicholas J., Danesh, John, Butterworth, Adam S., and Forouhi, Nita G.

Abstract

Background: Epidemiological evidence suggests that a potential association between dietary protein intake and cardiovascular disease (CVD) may depend on the protein source, that is, plant- or animal-derived, but past research was limited and inconclusive. Objectives: To evaluate the association of dietary plant- or animal-derived protein consumption with risk of CVD, and its components ischemic heart disease (IHD) and stroke. Methods: This analysis in the European Prospective Investigation into Cancer and Nutrition (EPIC)-CVD case–cohort study included 16,244 incident CVD cases (10,784 IHD and 6423 stroke cases) and 15,141 subcohort members from 7 European countries. We investigated the association of estimated dietary protein intake with CVD, IHD, and stroke (total, fatal, and nonfatal) using multivariable-adjusted Prentice-weighted Cox regression. We estimated isocaloric substitutions of replacing fats and carbohydrates with plant- or animal-derived protein and replacing food-specific animal protein with plant protein. Multiplicative interactions between dietary protein and prespecified variables were tested. Results: Neither plant- nor animal-derived protein intake was associated with incident CVD, IHD, or stroke in adjusted analyses without or with macronutrient-specified substitution analyses. Higher plant-derived protein intake was associated with 22% lower total stroke incidence among never smokers [HR 0.78, 95% confidence intervals (CI): 0.62, 0.99], but not among current smokers (HR 1.08, 95% CI: 0.83, 1.40, P-interaction = 0.004). Moreover, higher plant-derived protein (per 3% total energy) when replacing red meat protein (HR 0.52, 95% CI: 0.31, 0.88), processed meat protein (HR 0.39, 95% CI: 0.17, 0.90), and dairy protein (HR 0.54, 95% CI: 0.30, 0.98) was associated with lower incidence of fatal stroke.Conclusion: Plant- or animal-derived protein intake wa

Published
2024

42. A genomic approach to therapeutic target validation identifies a glucose-lowering GLP1R variant protective for coronary heart disease

Author

Scott, Robert A, Freitag, Daniel F, Li, Li, Chu, Audrey Y, Surendran, Praveen, Young, Robin, Grarup, Niels, Stancáková, Alena, Chen, Yuning, Varga, Tibor V, Yaghootkar, Hanieh, Luan, Jian’an, Zhao, Jing Hua, Willems, Sara M, Wessel, Jennifer, Wang, Shuai, Maruthur, Nisa, Michailidou, Kyriaki, Pirie, Ailith, van der Lee, Sven J, Gillson, Christopher, Al Olama, Ali Amin, Amouyel, Philippe, Arriola, Larraitz, Arveiler, Dominique, Aviles-Olmos, Iciar, Balkau, Beverley, Barricarte, Aurelio, Barroso, Inês, Garcia, Sara Benlloch, Bis, Joshua C, Blankenberg, Stefan, Boehnke, Michael, Boeing, Heiner, Boerwinkle, Eric, Borecki, Ingrid B, Bork-Jensen, Jette, Bowden, Sarah, Caldas, Carlos, Caslake, Muriel, consortium, The CVD50, Cupples, L Adrienne, Cruchaga, Carlos, Czajkowski, Jacek, Hoed, Marcel den, Dunn, Janet A, Earl, Helena M, Ehret, Georg B, Ferrannini, Ele, Ferrieres, Jean, Foltynie, Thomas, Ford, Ian, Forouhi, Nita G, Gianfagna, Francesco, Gonzalez, Carlos, Grioni, Sara, Hiller, Louise, Jansson, Jan-Håkan, Jørgensen, Marit E, Jukema, J Wouter, Kaaks, Rudolf, Kee, Frank, Kerrison, Nicola D, Key, Timothy J, Kontto, Jukka, Kote-Jarai, Zsofia, Kraja, Aldi T, Kuulasmaa, Kari, Kuusisto, Johanna, Linneberg, Allan, Liu, Chunyu, Marenne, Gaëlle, Mohlke, Karen L, Morris, Andrew P, Muir, Kenneth, Müller-Nurasyid, Martina, Munroe, Patricia B, Navarro, Carmen, Nielsen, Sune F, Nilsson, Peter M, Nordestgaard, Børge G, Packard, Chris J, Palli, Domenico, Panico, Salvatore, Peloso, Gina M, Perola, Markus, Peters, Annette, Poole, Christopher J, Quirós, J Ramón, Rolandsson, Olov, Sacerdote, Carlotta, Salomaa, Veikko, Sánchez, María-José, Sattar, Naveed, Sharp, Stephen J, Sims, Rebecca, Slimani, Nadia, Smith, Jennifer A, Thompson, Deborah J, and Trompet, Stella

Subjects
Pharmacology and Pharmaceutical Sciences, Biomedical and Clinical Sciences, Clinical Research, Diabetes, Human Genome, Cardiovascular, Prevention, Obesity, Genetics, Heart Disease, Heart Disease - Coronary Heart Disease, Clinical Trials and Supportive Activities, Aetiology, Development of treatments and therapeutic interventions, 5.1 Pharmaceuticals, 2.1 Biological and endogenous factors, Metabolic and endocrine, Good Health and Well Being, Alleles, Coronary Disease, Diabetes Mellitus, Type 2, Dipeptidyl Peptidase 4, Genotype, Glucagon-Like Peptide-1 Receptor, Humans, Receptor, Cannabinoid, CB2, Receptor, Serotonin, 5-HT2C, Receptors, Somatostatin, Sodium-Glucose Transporter 1, CVD50 consortium, GERAD_EC Consortium, Neurology Working Group of the Cohorts for Heart, Aging Research in Genomic Epidemiology, Alzheimer’s Disease Genetics Consortium, Pancreatic Cancer Cohort Consortium, European Prospective Investigation into Cancer and Nutrition–Cardiovascular Disease, EPIC-InterAct, CHARGE consortium, CHD Exome+ Consortium, CARDIOGRAM Exome Consortium, Biological Sciences, Medical and Health Sciences, Medical biotechnology, Biomedical engineering
Abstract

Regulatory authorities have indicated that new drugs to treat type 2 diabetes (T2D) should not be associated with an unacceptable increase in cardiovascular risk. Human genetics may be able to guide development of antidiabetic therapies by predicting cardiovascular and other health endpoints. We therefore investigated the association of variants in six genes that encode drug targets for obesity or T2D with a range of metabolic traits in up to 11,806 individuals by targeted exome sequencing and follow-up in 39,979 individuals by targeted genotyping, with additional in silico follow-up in consortia. We used these data to first compare associations of variants in genes encoding drug targets with the effects of pharmacological manipulation of those targets in clinical trials. We then tested the association of those variants with disease outcomes, including coronary heart disease, to predict cardiovascular safety of these agents. A low-frequency missense variant (Ala316Thr; rs10305492) in the gene encoding glucagon-like peptide-1 receptor (GLP1R), the target of GLP1R agonists, was associated with lower fasting glucose and T2D risk, consistent with GLP1R agonist therapies. The minor allele was also associated with protection against heart disease, thus providing evidence that GLP1R agonists are not likely to be associated with an unacceptable increase in cardiovascular risk. Our results provide an encouraging signal that these agents may be associated with benefit, a question currently being addressed in randomized controlled trials. Genetic variants associated with metabolic traits and multiple disease outcomes can be used to validate therapeutic targets at an early stage in the drug development process.

Published
2016

44. Autoimmunity plays a role in the onset of diabetes after 40 years of age

Author

Rolandsson, Olov, Hampe, Christiane S., Sharp, Stephen J., Ardanaz, Eva, Boeing, Heiner, Fagherazzi, Guy, Mancini, Francesca Romana, Nilsson, Peter M., Overvad, Kim, Chirlaque, Maria-Dolores, Dorronsoro, Miren, Gunter, Marc J., Kaaks, Rudolf, Key, Timothy J., Khaw, Kay-Tee, Krogh, Vittorio, Kühn, Tilman, Palli, Domenico, Panico, Salvatore, Sacerdote, Carlotta, Sánchez, Maria-José, Severi, Gianluca, Spijkerman, Annemieke M. W., Tumino, Rosario, van der Schouw, Yvonne T., Riboli, Elio, Forouhi, Nita G., Langenberg, Claudia, and Wareham, Nicholas J.

Published
2020
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45. HMG-coenzyme A reductase inhibition, type 2 diabetes, and bodyweight: evidence from genetic analysis and randomised trials

Author

Swerdlow, Daniel I, Preiss, David, Kuchenbaecker, Karoline B, Holmes, Michael V, Engmann, Jorgen EL, Shah, Tina, Sofat, Reecha, Stender, Stefan, Johnson, Paul CD, Scott, Robert A, Leusink, Maarten, Verweij, Niek, Sharp, Stephen J, Guo, Yiran, Giambartolomei, Claudia, Chung, Christina, Peasey, Anne, Amuzu, Antoinette, Li, KaWah, Palmen, Jutta, Howard, Philip, Cooper, Jackie A, Drenos, Fotios, Li, Yun R, Lowe, Gordon, Gallacher, John, Stewart, Marlene CW, Tzoulaki, Ioanna, Buxbaum, Sarah G, van der A, Daphne L, Forouhi, Nita G, Onland-Moret, N Charlotte, van der Schouw, Yvonne T, Schnabel, Renate B, Hubacek, Jaroslav A, Kubinova, Ruzena, Baceviciene, Migle, Tamosiunas, Abdonas, Pajak, Andrzej, Topor-Madry, Romanvan, Stepaniak, Urszula, Malyutina, Sofia, Baldassarre, Damiano, Sennblad, Bengt, Tremoli, Elena, de Faire, Ulf, Veglia, Fabrizio, Ford, Ian, Jukema, J Wouter, Westendorp, Rudi GJ, de Borst, Gert Jan, de Jong, Pim A, Algra, Ale, Spiering, Wilko, der Zee, Anke H Maitland-van, Klungel, Olaf H, de Boer, Anthonius, Doevendans, Pieter A, Eaton, Charles B, Robinson, Jennifer G, Duggan, David, DIAGRAM Consortium, MAGIC Consortium, Kjekshus, John, Downs, John R, Gotto, Antonio M, Keech, Anthony C, Marchioli, Roberto, Tognoni, Gianni, Sever, Peter S, Poulter, Neil R, Waters, David D, Pedersen, Terje R, Amarenco, Pierre, Nakamura, Haruo, McMurray, John JV, Lewsey, James D, Chasman, Daniel I, Ridker, Paul M, Maggioni, Aldo P, Tavazzi, Luigi, Ray, Kausik K, Seshasai, Sreenivasa Rao Kondapally, Manson, JoAnn E, Price, Jackie F, Whincup, Peter H, Morris, Richard W, Lawlor, Debbie A, Smith, George Davey, Ben-Shlomo, Yoav, Schreiner, Pamela J, Fornage, Myriam, Siscovick, David S, Cushman, Mary, Kumari, Meena, Wareham, Nick J, Verschuren, WM Monique, Redline, Susan, Patel, Sanjay R, Whittaker, John C, and Hamsten, Anders

Subjects
Epidemiology, Biomedical and Clinical Sciences, Health Sciences, Clinical Trials and Supportive Activities, Clinical Research, Genetics, Nutrition, Diabetes, 6.1 Pharmaceuticals, Evaluation of treatments and therapeutic interventions, Metabolic and endocrine, Aged, Body Mass Index, Body Weight, Cholesterol, HDL, Cholesterol, LDL, Diabetes Mellitus, Type 2, Female, Genetic Testing, Humans, Hydroxymethylglutaryl CoA Reductases, Hydroxymethylglutaryl-CoA Reductase Inhibitors, Male, Middle Aged, Polymorphism, Single Nucleotide, Randomized Controlled Trials as Topic, Risk Factors, DIAGRAM Consortium, MAGIC Consortium, InterAct Consortium, Medical and Health Sciences, General & Internal Medicine, Biomedical and clinical sciences, Health sciences
Abstract

BackgroundStatins increase the risk of new-onset type 2 diabetes mellitus. We aimed to assess whether this increase in risk is a consequence of inhibition of 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR), the intended drug target.MethodsWe used single nucleotide polymorphisms in the HMGCR gene, rs17238484 (for the main analysis) and rs12916 (for a subsidiary analysis) as proxies for HMGCR inhibition by statins. We examined associations of these variants with plasma lipid, glucose, and insulin concentrations; bodyweight; waist circumference; and prevalent and incident type 2 diabetes. Study-specific effect estimates per copy of each LDL-lowering allele were pooled by meta-analysis. These findings were compared with a meta-analysis of new-onset type 2 diabetes and bodyweight change data from randomised trials of statin drugs. The effects of statins in each randomised trial were assessed using meta-analysis.FindingsData were available for up to 223 463 individuals from 43 genetic studies. Each additional rs17238484-G allele was associated with a mean 0·06 mmol/L (95% CI 0·05-0·07) lower LDL cholesterol and higher body weight (0·30 kg, 0·18-0·43), waist circumference (0·32 cm, 0·16-0·47), plasma insulin concentration (1·62%, 0·53-2·72), and plasma glucose concentration (0·23%, 0·02-0·44). The rs12916 SNP had similar effects on LDL cholesterol, bodyweight, and waist circumference. The rs17238484-G allele seemed to be associated with higher risk of type 2 diabetes (odds ratio [OR] per allele 1·02, 95% CI 1·00-1·05); the rs12916-T allele association was consistent (1·06, 1·03-1·09). In 129 170 individuals in randomised trials, statins lowered LDL cholesterol by 0·92 mmol/L (95% CI 0·18-1·67) at 1-year of follow-up, increased bodyweight by 0·24 kg (95% CI 0·10-0·38 in all trials; 0·33 kg, 95% CI 0·24-0·42 in placebo or standard care controlled trials and -0·15 kg, 95% CI -0·39 to 0·08 in intensive-dose vs moderate-dose trials) at a mean of 4·2 years (range 1·9-6·7) of follow-up, and increased the odds of new-onset type 2 diabetes (OR 1·12, 95% CI 1·06-1·18 in all trials; 1·11, 95% CI 1·03-1·20 in placebo or standard care controlled trials and 1·12, 95% CI 1·04-1·22 in intensive-dose vs moderate dose trials).InterpretationThe increased risk of type 2 diabetes noted with statins is at least partially explained by HMGCR inhibition.FundingThe funding sources are cited at the end of the paper.

Published
2015

46. Sex-dimorphic genetic effects and novel loci for fasting glucose and insulin variability

Author

Lagou, Vasiliki, Mägi, Reedik, Hottenga, Jouke- Jan, Grallert, Harald, Perry, John R. B., Bouatia-Naji, Nabila, Marullo, Letizia, Rybin, Denis, Jansen, Rick, Min, Josine L., Dimas, Antigone S., Ulrich, Anna, Zudina, Liudmila, Gådin, Jesper R., Jiang, Longda, Faggian, Alessia, Bonnefond, Amélie, Fadista, Joao, Stathopoulou, Maria G., Isaacs, Aaron, Willems, Sara M., Navarro, Pau, Tanaka, Toshiko, Jackson, Anne U., Montasser, May E., O’Connell, Jeff R., Bielak, Lawrence F., Webster, Rebecca J., Saxena, Richa, Stafford, Jeanette M., Pourcain, Beate St, Timpson, Nicholas J., Salo, Perttu, Shin, So-Youn, Amin, Najaf, Smith, Albert V., Li, Guo, Verweij, Niek, Goel, Anuj, Ford, Ian, Johnson, Paul C. D., Johnson, Toby, Kapur, Karen, Thorleifsson, Gudmar, Strawbridge, Rona J., Rasmussen-Torvik, Laura J., Esko, Tõnu, Mihailov, Evelin, Fall, Tove, Fraser, Ross M., Mahajan, Anubha, Kanoni, Stavroula, Giedraitis, Vilmantas, Kleber, Marcus E., Silbernagel, Günther, Meyer, Julia, Müller-Nurasyid, Martina, Ganna, Andrea, Sarin, Antti-Pekka, Yengo, Loic, Shungin, Dmitry, Luan, Jian’an, Horikoshi, Momoko, An, Ping, Sanna, Serena, Boettcher, Yvonne, Rayner, N. William, Nolte, Ilja M., Zemunik, Tatijana, Iperen, Erik van, Kovacs, Peter, Hastie, Nicholas D., Wild, Sarah H., McLachlan, Stela, Campbell, Susan, Polasek, Ozren, Carlson, Olga, Egan, Josephine, Kiess, Wieland, Willemsen, Gonneke, Kuusisto, Johanna, Laakso, Markku, Dimitriou, Maria, Hicks, Andrew A., Rauramaa, Rainer, Bandinelli, Stefania, Thorand, Barbara, Liu, Yongmei, Miljkovic, Iva, Lind, Lars, Doney, Alex, Perola, Markus, Hingorani, Aroon, Kivimaki, Mika, Kumari, Meena, Bennett, Amanda J., Groves, Christopher J., Herder, Christian, Koistinen, Heikki A., Kinnunen, Leena, Faire, Ulf de, Bakker, Stephan J. L., Uusitupa, Matti, Palmer, Colin N. A., Jukema, J. Wouter, Sattar, Naveed, Pouta, Anneli, Snieder, Harold, Boerwinkle, Eric, Pankow, James S., Magnusson, Patrik K., Krus, Ulrika, Scapoli, Chiara, de Geus, Eco J. C. N., Blüher, Matthias, Wolffenbuttel, Bruce H. R., Province, Michael A., Abecasis, Goncalo R., Meigs, James B., Hovingh, G. Kees, Lindström, Jaana, Wilson, James F., Wright, Alan F., Dedoussis, George V., Bornstein, Stefan R., Schwarz, Peter E. H., Tönjes, Anke, Winkelmann, Bernhard R., Boehm, Bernhard O., März, Winfried, Metspalu, Andres, Price, Jackie F., Deloukas, Panos, Körner, Antje, Lakka, Timo A., Keinanen-Kiukaanniemi, Sirkka M., Saaristo, Timo E., Bergman, Richard N., Tuomilehto, Jaakko, Wareham, Nicholas J., Langenberg, Claudia, Männistö, Satu, Franks, Paul W., Hayward, Caroline, Vitart, Veronique, Kaprio, Jaakko, Visvikis-Siest, Sophie, Balkau, Beverley, Altshuler, David, Rudan, Igor, Stumvoll, Michael, Campbell, Harry, van Duijn, Cornelia M., Gieger, Christian, Illig, Thomas, Ferrucci, Luigi, Pedersen, Nancy L., Pramstaller, Peter P., Boehnke, Michael, Frayling, Timothy M., Shuldiner, Alan R., Peyser, Patricia A., Kardia, Sharon L. R., Palmer, Lyle J., Penninx, Brenda W., Meneton, Pierre, Harris, Tamara B., Navis, Gerjan, Harst, Pim van der, Smith, George Davey, Forouhi, Nita G., Loos, Ruth J. F., Salomaa, Veikko, Soranzo, Nicole, Boomsma, Dorret I., Groop, Leif, Tuomi, Tiinamaija, Hofman, Albert, Munroe, Patricia B., Gudnason, Vilmundur, Siscovick, David S., Watkins, Hugh, Lecoeur, Cecile, Vollenweider, Peter, Franco-Cereceda, Anders, Eriksson, Per, Jarvelin, Marjo-Riitta, Stefansson, Kari, Hamsten, Anders, Nicholson, George, Karpe, Fredrik, Dermitzakis, Emmanouil T., Lindgren, Cecilia M., McCarthy, Mark I., Froguel, Philippe, Kaakinen, Marika A., Lyssenko, Valeriya, Watanabe, Richard M., Ingelsson, Erik, Florez, Jose C., Dupuis, Josée, Barroso, Inês, Morris, Andrew P., and Prokopenko, Inga

Published
2021
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47. Blood n-3 fatty acid levels and total and cause-specific mortality from 17 prospective studies

Author

Harris, William S., Tintle, Nathan L., Imamura, Fumiaki, Qian, Frank, Korat, Andres V. Ardisson, Marklund, Matti, Djoussé, Luc, Bassett, Julie K., Carmichael, Pierre-Hugues, Chen, Yun-Yu, Hirakawa, Yoichiro, Küpers, Leanne K., Laguzzi, Federica, Lankinen, Maria, Murphy, Rachel A., Samieri, Cécilia, Senn, Mackenzie K., Shi, Peilin, Virtanen, Jyrki K., Brouwer, Ingeborg A., Chien, Kuo-Liong, Eiriksdottir, Gudny, Forouhi, Nita G., Geleijnse, Johanna M., Giles, Graham G., Gudnason, Vilmundur, Helmer, Catherine, Hodge, Allison, Jackson, Rebecca, Khaw, Kay-Tee, Laakso, Markku, Lai, Heidi, Laurin, Danielle, Leander, Karin, Lindsay, Joan, Micha, Renata, Mursu, Jaako, Ninomiya, Toshiharu, Post, Wendy, Psaty, Bruce M., Risérus, Ulf, Robinson, Jennifer G., Shadyab, Aladdin H., Snetselaar, Linda, Sala-Vila, Aleix, Sun, Yangbo, Steffen, Lyn M., Tsai, Michael Y., Wareham, Nicholas J., Wood, Alexis C., Wu, Jason H. Y., Hu, Frank, Sun, Qi, Siscovick, David S., Lemaitre, Rozenn N., and Mozaffarian, Dariush

Published
2021
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50. Genome-wide trans-ancestry meta-analysis provides insight into the genetic architecture of type 2 diabetes susceptibility

Author

Mahajan, Anubha, Go, Min Jin, Zhang, Weihua, Below, Jennifer E, Gaulton, Kyle J, Ferreira, Teresa, Horikoshi, Momoko, Johnson, Andrew D, Ng, Maggie CY, Prokopenko, Inga, Saleheen, Danish, Wang, Xu, Zeggini, Eleftheria, Abecasis, Goncalo R, Adair, Linda S, Almgren, Peter, Atalay, Mustafa, Aung, Tin, Baldassarre, Damiano, Balkau, Beverley, Bao, Yuqian, Barnett, Anthony H, Barroso, Ines, Basit, Abdul, Been, Latonya F, Beilby, John, Bell, Graeme I, Benediktsson, Rafn, Bergman, Richard N, Boehm, Bernhard O, Boerwinkle, Eric, Bonnycastle, Lori L, Burtt, Noël, Cai, Qiuyin, Campbell, Harry, Carey, Jason, Cauchi, Stephane, Caulfield, Mark, Chan, Juliana CN, Chang, Li-Ching, Chang, Tien-Jyun, Chang, Yi-Cheng, Charpentier, Guillaume, Chen, Chien-Hsiun, Chen, Han, Chen, Yuan-Tsong, Chia, Kee-Seng, Chidambaram, Manickam, Chines, Peter S, Cho, Nam H, Cho, Young Min, Chuang, Lee-Ming, Collins, Francis S, Cornelis, Marilyn C, Couper, David J, Crenshaw, Andrew T, van Dam, Rob M, Danesh, John, Das, Debashish, de Faire, Ulf, Dedoussis, George, Deloukas, Panos, Dimas, Antigone S, Dina, Christian, Doney, Alex SF, Donnelly, Peter J, Dorkhan, Mozhgan, van Duijn, Cornelia, Dupuis, Josée, Edkins, Sarah, Elliott, Paul, Emilsson, Valur, Erbel, Raimund, Eriksson, Johan G, Escobedo, Jorge, Esko, Tonu, Eury, Elodie, Florez, Jose C, Fontanillas, Pierre, Forouhi, Nita G, Forsen, Tom, Fox, Caroline, Fraser, Ross M, Frayling, Timothy M, Froguel, Philippe, Frossard, Philippe, Gao, Yutang, Gertow, Karl, Gieger, Christian, Gigante, Bruna, Grallert, Harald, Grant, George B, Groop, Leif C, Groves, Christopher J, Grundberg, Elin, Guiducci, Candace, Hamsten, Anders, Han, Bok-Ghee, Hara, Kazuo, and Hassanali, Neelam

Subjects
Biological Sciences, Genetics, Human Genome, Diabetes, Metabolic and endocrine, Alleles, Asian People, Case-Control Studies, Diabetes Mellitus, Type 2, Genetic Predisposition to Disease, Genome-Wide Association Study, Hispanic or Latino, Humans, Polymorphism, Single Nucleotide, Risk Factors, White People, DIAbetes Genetics Replication And Meta-analysis (DIAGRAM) Consortium, Asian Genetic Epidemiology Network Type 2 Diabetes (AGEN-T2D) Consortium, South Asian Type 2 Diabetes (SAT2D) Consortium, Mexican American Type 2 Diabetes (MAT2D) Consortium, Type 2 Diabetes Genetic Exploration by Nex-generation sequencing in muylti-Ethnic Samples (T2D-GENES) Consortium, Medical and Health Sciences, Developmental Biology, Agricultural biotechnology, Bioinformatics and computational biology
Abstract

To further understanding of the genetic basis of type 2 diabetes (T2D) susceptibility, we aggregated published meta-analyses of genome-wide association studies (GWAS), including 26,488 cases and 83,964 controls of European, east Asian, south Asian and Mexican and Mexican American ancestry. We observed a significant excess in the directional consistency of T2D risk alleles across ancestry groups, even at SNPs demonstrating only weak evidence of association. By following up the strongest signals of association from the trans-ethnic meta-analysis in an additional 21,491 cases and 55,647 controls of European ancestry, we identified seven new T2D susceptibility loci. Furthermore, we observed considerable improvements in the fine-mapping resolution of common variant association signals at several T2D susceptibility loci. These observations highlight the benefits of trans-ethnic GWAS for the discovery and characterization of complex trait loci and emphasize an exciting opportunity to extend insight into the genetic architecture and pathogenesis of human diseases across populations of diverse ancestry.

Published
2014

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