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1. 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

3. 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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4. Causal analysis of plasma IL-8 on carotid intima media thickness, a measure of subclinical atherosclerosis

Author

Velásquez, Ilais Moreno, Malarstig, Anders, Baldassarre, Damiano, Borne, Yan, de Faire, Ulf, Engström, Gunnar, Eriksson, Per, Giral, Philippe, Humphries, Steve E., Kurl, Sudhir, Leander, Karin, Lind, Lars, Lindén, Anders, Orsini, Nicola, Pirro, Matteo, Silveira, Angela, Smit, Andries J., Tremoli, Elena, Veglia, Fabrizio, Strawbridge, Rona J., and Gigante, Bruna

Published
2023
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5. Multiancestry Genome-Wide Association Study of Lipid Levels Incorporating Gene-Alcohol Interactions

Author

de Vries, Paul S, Brown, Michael R, Bentley, Amy R, Sung, Yun J, Winkler, Thomas W, Ntalla, Ioanna, Schwander, Karen, Kraja, Aldi T, Guo, Xiuqing, Franceschini, Nora, Cheng, Ching-Yu, Sim, Xueling, Vojinovic, Dina, Huffman, Jennifer E, Musani, Solomon K, Li, Changwei, Feitosa, Mary F, Richard, Melissa A, Noordam, Raymond, Aschard, Hugues, Bartz, Traci M, Bielak, Lawrence F, Deng, Xuan, Dorajoo, Rajkumar, Lohman, Kurt K, Manning, Alisa K, Rankinen, Tuomo, Smith, Albert V, Tajuddin, Salman M, Evangelou, Evangelos, Graff, Mariaelisa, Alver, Maris, Boissel, Mathilde, Chai, Jin Fang, Chen, Xu, Divers, Jasmin, Gandin, Ilaria, Gao, Chuan, Goel, Anuj, Hagemeijer, Yanick, Harris, Sarah E, Hartwig, Fernando P, He, Meian, Horimoto, Andrea RVR, Hsu, Fang-Chi, Jackson, Anne U, Kasturiratne, Anuradhani, Komulainen, Pirjo, Kühnel, Brigitte, Laguzzi, Federica, Lee, Joseph H, Luan, Jian'an, Lyytikäinen, Leo-Pekka, Matoba, Nana, Nolte, Ilja M, Pietzner, Maik, Riaz, Muhammad, Said, M Abdullah, Scott, Robert A, Sofer, Tamar, Stančáková, Alena, Takeuchi, Fumihiko, Tayo, Bamidele O, van der Most, Peter J, Varga, Tibor V, Wang, Yajuan, Ware, Erin B, Wen, Wanqing, Yanek, Lisa R, Zhang, Weihua, Zhao, Jing Hua, Afaq, Saima, Amin, Najaf, Amini, Marzyeh, Arking, Dan E, Aung, Tin, Ballantyne, Christie, Boerwinkle, Eric, Broeckel, Ulrich, Campbell, Archie, Canouil, Mickaël, Charumathi, Sabanayagam, Chen, Yii-Der Ida, Connell, John M, de Faire, Ulf, de las Fuentes, Lisa, de Mutsert, Renée, de Silva, H Janaka, Ding, Jingzhong, Dominiczak, Anna F, Duan, Qing, Eaton, Charles B, Eppinga, Ruben N, Faul, Jessica D, Fisher, Virginia, Forrester, Terrence, Franco, Oscar H, Friedlander, Yechiel, Ghanbari, Mohsen, and Giulianini, Franco

Subjects
Epidemiology, Health Sciences, Atherosclerosis, Substance Misuse, Human Genome, Alcoholism, Alcohol Use and Health, Genetics, 2.1 Biological and endogenous factors, Cardiovascular, Adolescent, Adult, Aged, Alcohol Drinking, Cholesterol, HDL, Cholesterol, LDL, Female, Genome-Wide Association Study, Genotype, Humans, Life Style, Lipids, Male, Middle Aged, Phenotype, Racial Groups, Triglycerides, Vascular Endothelial Growth Factor B, Young Adult, alcohol consumption, cholesterol, gene-environment interactions, gene-lifestyle interactions, genome-wide association studies, lipids, triglycerides, InterAct Consortium, Lifelines Cohort, Groningen, The Netherlands, Mathematical Sciences, Medical and Health Sciences
Abstract

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

Published
2019

6. Does Periodontitis Increase the Risk for Future Cardiovascular Events? Long‐Term Follow‐Up of the PAROKRANK Study.

Author

Norhammar, Anna, Näsman, Per, Buhlin, Kåre, de Faire, Ulf, Ferrannini, Giulia, Gustafsson, Anders, Kjellström, Barbro, Kvist, Thomas, Jäghagen, Eva Levring, Lindahl, Bertil, Nygren, Åke, Näslund, Ulf, Svenungsson, Elisabet, Klinge, Björn, and Rydén, Lars

Subjects
MYOCARDIAL infarction risk factors, HEART failure risk factors, RISK assessment, CARDIOVASCULAR diseases risk factors, DESCRIPTIVE statistics, KAPLAN-Meier estimator, PANORAMIC radiography, STROKE, CONFIDENCE intervals, PERIODONTITIS, PROPORTIONAL hazards models, REGRESSION analysis, DISEASE risk factors, DISEASE complications
Abstract

Background and Aim: The study 'Periodontitis and Its Relation to Coronary Artery Disease' (PAROKRANK) reported an association between periodontitis (PD) and the first myocardial infarction (MI). This follow‐up study aims to test the hypothesis that those with PD—compared to periodontally healthy individuals—are at increased risk for cardiovascular (CV) events and death. Methods: A total of 1587 participants (age <75 years; females 19%) had a dental examination including panoramic radiographs between 2010 and 2014. PD was categorized as healthy (≥80% alveolar bone height), mild/moderate (79%–66%) or severe (<66%). A composite CV event (first of all‐cause death, non‐fatal MI or stroke and hospitalization following to heart failure) was investigated during a mean follow‐up period of 9.9 years (range 0.2–12.5 years). Participants were divided into two groups: those with and without PD. The primary event rate, stratified by periodontal status at baseline, was calculated using the Kaplan–Meier method and Cox regression. Results: The number of events was 187 in the 985 periodontally healthy participants (19%) and 174 in the 602 participants with PD (29%; p < 0.0001). Those with PD had a higher likelihood for a future event (hazard ratio [HR] = 1.26; 95% CI: 1.01–1.57; p = 0.038), following adjustment for age, smoking and diabetes. Conclusion: The PAROKRANK follow‐up revealed that CV events were more common among participants with PD, which supports the assumption that there might be a direct relation between PD and CV disease. [ABSTRACT FROM AUTHOR]

Published
2025
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8. Long-term exposure to low-level ambient air pollution and incidence of stroke and coronary heart disease: a pooled analysis of six European cohorts within the ELAPSE project

Author

Wolf, Kathrin, Hoffmann, Barbara, Andersen, Zorana J, Atkinson, Richard W, Bauwelinck, Mariska, Bellander, Tom, Brandt, Jørgen, Brunekreef, Bert, Cesaroni, Giulia, Chen, Jie, de Faire, Ulf, de Hoogh, Kees, Fecht, Daniela, Forastiere, Francesco, Gulliver, John, Hertel, Ole, Hvidtfeldt, Ulla Arthur, Janssen, Nicole A H, Jørgensen, Jeanette T, Katsouyanni, Klea, Ketzel, Matthias, Klompmaker, Jochem O, Lager, Anton, Liu, Shuo, MacDonald, Conor J, Magnusson, Patrik K E, Mehta, Amar J, Nagel, Gabriele, Oftedal, Bente, Pedersen, Nancy L, Pershagen, Göran, Raaschou-Nielsen, Ole, Renzi, Matteo, Rizzuto, Debora, Rodopoulou, Sophia, Samoli, Evangelia, van der Schouw, Yvonne T, Schramm, Sara, Schwarze, Per, Sigsgaard, Torben, Sørensen, Mette, Stafoggia, Massimo, Strak, Maciek, Tjønneland, Anne, Verschuren, W M Monique, Vienneau, Danielle, Weinmayr, Gudrun, Hoek, Gerard, Peters, Annette, and Ljungman, Petter L S

Published
2021
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9. The genetics of blood pressure regulation and its target organs from association studies in 342,415 individuals.

Author

Ehret, Georg B, Ferreira, Teresa, Chasman, Daniel I, Jackson, Anne U, Schmidt, Ellen M, Johnson, Toby, Thorleifsson, Gudmar, Luan, Jian'an, Donnelly, Lousie A, Kanoni, Stavroula, Petersen, Ann-Kristin, Pihur, Vasyl, Strawbridge, Rona J, Shungin, Dmitry, Hughes, Maria F, Meirelles, Osorio, Kaakinen, Marika, Bouatia-Naji, Nabila, Kristiansson, Kati, Shah, Sonia, Kleber, Marcus E, Guo, Xiuqing, Lyytikäinen, Leo-Pekka, Fava, Cristiano, Eriksson, Niclas, Nolte, Ilja M, Magnusson, Patrik K, Salfati, Elias L, Rallidis, Loukianos S, Theusch, Elizabeth, Smith, Andrew JP, Folkersen, Lasse, Witkowska, Kate, Pers, Tune H, Joehanes, Roby, Kim, Stuart K, Lataniotis, Lazaros, Jansen, Rick, Johnson, Andrew D, Warren, Helen, Kim, Young Jin, Zhao, Wei, Wu, Ying, Tayo, Bamidele O, Bochud, Murielle, CHARGE-EchoGen consortium, CHARGE-HF consortium, Wellcome Trust Case Control Consortium, Absher, Devin, Adair, Linda S, Amin, Najaf, Arking, Dan E, Axelsson, Tomas, Baldassarre, Damiano, Balkau, Beverley, Bandinelli, Stefania, Barnes, Michael R, Barroso, Inês, Bevan, Stephen, Bis, Joshua C, Bjornsdottir, Gyda, Boehnke, Michael, Boerwinkle, Eric, Bonnycastle, Lori L, Boomsma, Dorret I, Bornstein, Stefan R, Brown, Morris J, Burnier, Michel, Cabrera, Claudia P, Chambers, John C, Chang, I-Shou, Cheng, Ching-Yu, Chines, Peter S, Chung, Ren-Hua, Collins, Francis S, Connell, John M, Döring, Angela, Dallongeville, Jean, Danesh, John, de Faire, Ulf, Delgado, Graciela, Dominiczak, Anna F, Doney, Alex SF, Drenos, Fotios, Edkins, Sarah, Eicher, John D, Elosua, Roberto, Enroth, Stefan, Erdmann, Jeanette, Eriksson, Per, Esko, Tonu, Evangelou, Evangelos, Evans, Alun, Fall, Tove, Farrall, Martin, Felix, Janine F, Ferrières, Jean, Ferrucci, Luigi, Fornage, Myriam, and Forrester, Terrence

Subjects
CHARGE-EchoGen consortium, CHARGE-HF consortium, Wellcome Trust Case Control Consortium, Cells, Cultured, Humans, Hypertension, Microarray Analysis, Blood Pressure, Polymorphism, Single Nucleotide, African Continental Ancestry Group, Asian Continental Ancestry Group, Genome-Wide Association Study, Cells, Cultured, Polymorphism, Single Nucleotide, Developmental Biology, Biological Sciences, Medical and Health Sciences
Abstract

To dissect the genetic architecture of blood pressure and assess effects on target organ damage, we analyzed 128,272 SNPs from targeted and genome-wide arrays in 201,529 individuals of European ancestry, and genotypes from an additional 140,886 individuals were used for validation. We identified 66 blood pressure-associated loci, of which 17 were new; 15 harbored multiple distinct association signals. The 66 index SNPs were enriched for cis-regulatory elements, particularly in vascular endothelial cells, consistent with a primary role in blood pressure control through modulation of vascular tone across multiple tissues. The 66 index SNPs combined in a risk score showed comparable effects in 64,421 individuals of non-European descent. The 66-SNP blood pressure risk score was significantly associated with target organ damage in multiple tissues but with minor effects in the kidney. Our findings expand current knowledge of blood pressure-related pathways and highlight tissues beyond the classical renal system in blood pressure regulation.

Published
2016

11. Does periodontitis increase the risk for future cardiovascular events? : Long-term follow-up of the PAROKRANK study

Author

Norhammar, Anna, Näsman, Per, Buhlin, Kåre, de Faire, Ulf, Ferrannini, Giulia, Gustafsson, Anders, Kjellström, Barbro, Kvist, Thomas, Levring Jäghagen, Eva, Lindahl, Bertil, Nygren, Åke, Näslund, Ulf, Svenungsson, Elisabet, Klinge, Björn, Rydén, Lars, Norhammar, Anna, Näsman, Per, Buhlin, Kåre, de Faire, Ulf, Ferrannini, Giulia, Gustafsson, Anders, Kjellström, Barbro, Kvist, Thomas, Levring Jäghagen, Eva, Lindahl, Bertil, Nygren, Åke, Näslund, Ulf, Svenungsson, Elisabet, Klinge, Björn, and Rydén, Lars

Abstract

Background and Aim: The study ‘Periodontitis and Its Relation to Coronary Artery Disease’ (PAROKRANK) reported an association between periodontitis (PD) and the first myocardial infarction (MI). This follow-up study aims to test the hypothesis that those with PD—compared to periodontally healthy individuals—are at increased risk for cardiovascular (CV) events and death. Methods: A total of 1587 participants (age <75 years; females 19%) had a dental examination including panoramic radiographs between 2010 and 2014. PD was categorized as healthy (≥80% alveolar bone height), mild/moderate (79%–66%) or severe (<66%). A composite CV event (first of all-cause death, non-fatal MI or stroke and hospitalization following to heart failure) was investigated during a mean follow-up period of 9.9 years (range 0.2–12.5 years). Participants were divided into two groups: those with and without PD. The primary event rate, stratified by periodontal status at baseline, was calculated using the Kaplan–Meier method and Cox regression. Results: The number of events was 187 in the 985 periodontally healthy participants (19%) and 174 in the 602 participants with PD (29%; p < 0.0001). Those with PD had a higher likelihood for a future event (hazard ratio [HR] = 1.26; 95% CI: 1.01–1.57; p = 0.038), following adjustment for age, smoking and diabetes. Conclusion: The PAROKRANK follow-up revealed that CV events were more common among participants with PD, which supports the assumption that there might be a direct relation between PD and CV disease.

Published
2024
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14. A priori-defined Mediterranean-like dietary pattern predicts cardiovascular events better in north Europe than in Mediterranean countries

Author

Veglia, Fabrizio, Baldassarre, Damiano, de Faire, Ulf, Kurl, Sudhir, Smit, Andries J., Rauramaa, Rainer, Giral, Philippe, Amato, Mauro, Di Minno, Alessandro, Ravani, Alessio, Frigerio, Beatrice, Castelnuovo, Samuela, Sansaro, Daniela, Coggi, Daniela, Bonomi, Alice, Tedesco, Calogero C., Mannarino, Elmo, Humphries, Steve E., Hamsten, Anders, and Tremoli, Elena

Published
2019
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15. 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

16. 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

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

Author

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, 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, Marylin 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 S, 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, Grrop, Leif C, and Groves, Chrisropher J

Subjects
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, Humans, Diabetes Mellitus, Type 2, Genetic Predisposition to Disease, Risk Factors, Case-Control Studies, Polymorphism, Single Nucleotide, Alleles, Asian Continental Ancestry Group, European Continental Ancestry Group, Hispanic Americans, Genome-Wide Association Study, Diabetes Mellitus, Type 2, Polymorphism, Single Nucleotide, Biological Sciences, Medical and Health Sciences, Developmental 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

18. Gene-educational attainment interactions in a multi-population genome-wide meta-analysis identify novel lipid loci

Author

de las Fuentes, Lisa, primary, Schwander, Karen L., additional, Brown, Michael R., additional, Bentley, Amy R., additional, Winkler, Thomas W., additional, Sung, Yun Ju, additional, Munroe, Patricia B., additional, Miller, Clint L., additional, Aschard, Hugo, additional, Aslibekyan, Stella, additional, Bartz, Traci M., additional, Bielak, Lawrence F., additional, Chai, Jin Fang, additional, Cheng, Ching-Yu, additional, Dorajoo, Rajkumar, additional, Feitosa, Mary F., additional, Guo, Xiuqing, additional, Hartwig, Fernando P., additional, Horimoto, Andrea, additional, Kolčić, Ivana, additional, Lim, Elise, additional, Liu, Yongmei, additional, Manning, Alisa K., additional, Marten, Jonathan, additional, Musani, Solomon K., additional, Noordam, Raymond, additional, Padmanabhan, Sandosh, additional, Rankinen, Tuomo, additional, Richard, Melissa A., additional, Ridker, Paul M., additional, Smith, Albert V., additional, Vojinovic, Dina, additional, Zonderman, Alan B., additional, Alver, Maris, additional, Boissel, Mathilde, additional, Christensen, Kaare, additional, Freedman, Barry I., additional, Gao, Chuan, additional, Giulianini, Franco, additional, Harris, Sarah E., additional, He, Meian, additional, Hsu, Fang-Chi, additional, Kühnel, Brigitte, additional, Laguzzi, Federica, additional, Li, Xiaoyin, additional, Lyytikäinen, Leo-Pekka, additional, Nolte, Ilja M., additional, Poveda, Alaitz, additional, Rauramaa, Rainer, additional, Riaz, Muhammad, additional, Robino, Antonietta, additional, Sofer, Tamar, additional, Takeuchi, Fumihiko, additional, Tayo, Bamidele O., additional, van der Most, Peter J., additional, Verweij, Niek, additional, Ware, Erin B., additional, Weiss, Stefan, additional, Wen, Wanqing, additional, Yanek, Lisa R., additional, Zhan, Yiqiang, additional, Amin, Najaf, additional, Arking, Dan E., additional, Ballantyne, Christie, additional, Boerwinkle, Eric, additional, Brody, Jennifer A., additional, Broeckel, Ulrich, additional, Campbell, Archie, additional, Canouil, Mickaël, additional, Chai, Xiaoran, additional, Chen, Yii-Der Ida, additional, Chen, Xu, additional, Chitrala, Kumaraswamy Naidu, additional, Concas, Maria Pina, additional, de Faire, Ulf, additional, de Mutsert, Renée, additional, de Silva, H. Janaka, additional, de Vries, Paul S., additional, Do, Ahn, additional, Faul, Jessica D., additional, Fisher, Virginia, additional, Floyd, James S., additional, Forrester, Terrence, additional, Friedlander, Yechiel, additional, Girotto, Giorgia, additional, Gu, C. Charles, additional, Hallmans, Göran, additional, Heikkinen, Sami, additional, Heng, Chew-Kiat, additional, Homuth, Georg, additional, Hunt, Steven, additional, Ikram, M. Arfan, additional, Jacobs, David R., additional, Kavousi, Maryam, additional, Khor, Chiea Chuen, additional, Kilpeläinen, Tuomas O., additional, Koh, Woon-Puay, additional, Komulainen, Pirjo, additional, Langefeld, Carl D., additional, Liang, Jingjing, additional, Liu, Kiang, additional, Liu, Jianjun, additional, Lohman, Kurt, additional, Mägi, Reedik, additional, Manichaikul, Ani W., additional, McKenzie, Colin A., additional, Meitinger, Thomas, additional, Milaneschi, Yuri, additional, Nauck, Matthias, additional, Nelson, Christopher P., additional, O’Connell, Jeffrey R., additional, Palmer, Nicholette D., additional, Pereira, Alexandre C., additional, Perls, Thomas, additional, Peters, Annette, additional, Polašek, Ozren, additional, Raitakari, Olli T., additional, Rice, Kenneth, additional, Rice, Treva K., additional, Rich, Stephen S., additional, Sabanayagam, Charumathi, additional, Schreiner, Pamela J., additional, Shu, Xiao-Ou, additional, Sidney, Stephen, additional, Sims, Mario, additional, Smith, Jennifer A., additional, Starr, John M., additional, Strauch, Konstantin, additional, Tai, E. Shyong, additional, Taylor, Kent D., additional, Tsai, Michael Y., additional, Uitterlinden, André G., additional, van Heemst, Diana, additional, Waldenberger, Melanie, additional, Wang, Ya-Xing, additional, Wei, Wen-Bin, additional, Wilson, Gregory, additional, Xuan, Deng, additional, Yao, Jie, additional, Yu, Caizheng, additional, Yuan, Jian-Min, additional, Zhao, Wei, additional, Becker, Diane M., additional, Bonnefond, Amélie, additional, Bowden, Donald W., additional, Cooper, Richard S., additional, Deary, Ian J., additional, Divers, Jasmin, additional, Esko, Tõnu, additional, Franks, Paul W., additional, Froguel, Philippe, additional, Gieger, Christian, additional, Jonas, Jost B., additional, Kato, Norihiro, additional, Lakka, Timo A., additional, Leander, Karin, additional, Lehtimäki, Terho, additional, Magnusson, Patrik K. E., additional, North, Kari E., additional, Ntalla, Ioanna, additional, Penninx, Brenda, additional, Samani, Nilesh J., additional, Snieder, Harold, additional, Spedicati, Beatrice, additional, van der Harst, Pim, additional, Völzke, Henry, additional, Wagenknecht, Lynne E., additional, Weir, David R., additional, Wojczynski, Mary K., additional, Wu, Tangchun, additional, Zheng, Wei, additional, Zhu, Xiaofeng, additional, Bouchard, Claude, additional, Chasman, Daniel I., additional, Evans, Michele K., additional, Fox, Ervin R., additional, Gudnason, Vilmundur, additional, Hayward, Caroline, additional, Horta, Bernardo L., additional, Kardia, Sharon L. R., additional, Krieger, Jose Eduardo, additional, Mook-Kanamori, Dennis O., additional, Peyser, Patricia A., additional, Province, Michael M., additional, Psaty, Bruce M., additional, Rudan, Igor, additional, Sim, Xueling, additional, Smith, Blair H., additional, van Dam, Rob M., additional, van Duijn, Cornelia M., additional, Wong, Tien Yin, additional, Arnett, Donna K., additional, Rao, Dabeeru C., additional, Gauderman, James, additional, Liu, Ching-Ti, additional, Morrison, Alanna C., additional, Rotter, Jerome I., additional, and Fornage, Myriam, additional

Published
2023
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19. Particulate matter air pollution components and incidence of cancers of the stomach and the upper aerodigestive tract in the European Study of Cohorts of Air Pollution Effects (ESCAPE)

Author

Weinmayr, Gudrun, Pedersen, Marie, Stafoggia, Massimo, Andersen, Zorana J., Galassi, Claudia, Munkenast, Jule, Jaensch, Andrea, Oftedal, Bente, Krog, Norun H., Aamodt, Geir, Pyko, Andrei, Pershagen, Göran, Korek, Michal, De Faire, Ulf, Pedersen, Nancy L., Östenson, Claes-Göran, Rizzuto, Debora, Sørensen, Mette, Tjønneland, Anne, Bueno-de-Mesquita, Bas, Vermeulen, Roel, Eeftens, Marloes, Concin, Hans, Lang, Alois, Wang, Meng, Tsai, Ming-Yi, Ricceri, Fulvio, Sacerdote, Carlotta, Ranzi, Andrea, Cesaroni, Giulia, Forastiere, Francesco, de Hoogh, Kees, Beelen, Rob, Vineis, Paolo, Kooter, Ingeborg, Sokhi, Ranjeet, Brunekreef, Bert, Hoek, Gerard, Raaschou-Nielsen, Ole, and Nagel, Gabriele

Published
2018
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20. A Large-Scale Multi-ancestry Genome-wide Study Accounting for Smoking Behavior Identifies Multiple Significant Loci for Blood Pressure

Author

Sung, Yun J., Winkler, Thomas W., de las Fuentes, Lisa, Bentley, Amy R., Brown, Michael R., Kraja, Aldi T., Schwander, Karen, Ntalla, Ioanna, Guo, Xiuqing, Franceschini, Nora, Lu, Yingchang, Cheng, Ching-Yu, Sim, Xueling, Vojinovic, Dina, Marten, Jonathan, Musani, Solomon K., Li, Changwei, Feitosa, Mary F., Kilpeläinen, Tuomas O., Richard, Melissa A., Noordam, Raymond, Aslibekyan, Stella, Aschard, Hugues, Bartz, Traci M., Dorajoo, Rajkumar, Liu, Yongmei, Manning, Alisa K., Rankinen, Tuomo, Smith, Albert Vernon, Tajuddin, Salman M., Tayo, Bamidele O., Warren, Helen R., Zhao, Wei, Zhou, Yanhua, Matoba, Nana, Sofer, Tamar, Alver, Maris, Amini, Marzyeh, Boissel, Mathilde, Chai, Jin Fang, Chen, Xu, Divers, Jasmin, Gandin, Ilaria, Gao, Chuan, Giulianini, Franco, Goel, Anuj, Harris, Sarah E., Hartwig, Fernando Pires, Horimoto, Andrea R.V.R., Hsu, Fang-Chi, Jackson, Anne U., Kähönen, Mika, Kasturiratne, Anuradhani, Kühnel, Brigitte, Leander, Karin, Lee, Wen-Jane, Lin, Keng-Hung, ’an Luan, Jian, McKenzie, Colin A., Meian, He, Nelson, Christopher P., Rauramaa, Rainer, Schupf, Nicole, Scott, Robert A., Sheu, Wayne H.H., Stančáková, Alena, Takeuchi, Fumihiko, van der Most, Peter J., Varga, Tibor V., Wang, Heming, Wang, Yajuan, Ware, Erin B., Weiss, Stefan, Wen, Wanqing, Yanek, Lisa R., Zhang, Weihua, Zhao, Jing Hua, Afaq, Saima, Alfred, Tamuno, Amin, Najaf, Arking, Dan, Aung, Tin, Barr, R. Graham, Bielak, Lawrence F., Boerwinkle, Eric, Bottinger, Erwin P., Braund, Peter S., Brody, Jennifer A., Broeckel, Ulrich, Cabrera, Claudia P., Cade, Brian, Caizheng, Yu, Campbell, Archie, Canouil, Mickaël, Chakravarti, Aravinda, Chauhan, Ganesh, Christensen, Kaare, Cocca, Massimiliano, Collins, Francis S., Connell, John M., de Mutsert, Renée, de Silva, H. Janaka, Debette, Stephanie, Dörr, Marcus, Duan, Qing, Eaton, Charles B., Ehret, Georg, Evangelou, Evangelos, Faul, Jessica D., Fisher, Virginia A., Forouhi, Nita G., Franco, Oscar H., Friedlander, Yechiel, Gao, He, Gigante, Bruna, Graff, Misa, Gu, C. Charles, Gu, Dongfeng, Gupta, Preeti, Hagenaars, Saskia P., Harris, Tamara B., He, Jiang, Heikkinen, Sami, Heng, Chew-Kiat, Hirata, Makoto, Hofman, Albert, Howard, Barbara V., Hunt, Steven, Irvin, Marguerite R., Jia, Yucheng, Joehanes, Roby, Justice, Anne E., Katsuya, Tomohiro, Kaufman, Joel, Kerrison, Nicola D., Khor, Chiea Chuen, Koh, Woon-Puay, Koistinen, Heikki A., Komulainen, Pirjo, Kooperberg, Charles, Krieger, Jose E., Kubo, Michiaki, Kuusisto, Johanna, Langefeld, Carl D., Langenberg, Claudia, Launer, Lenore J., Lehne, Benjamin, Lewis, Cora E., Li, Yize, Lim, Sing Hui, Lin, Shiow, Liu, Ching-Ti, Liu, Jianjun, Liu, Jingmin, Liu, Kiang, Liu, Yeheng, Loh, Marie, Lohman, Kurt K., Long, Jirong, Louie, Tin, Mägi, Reedik, Mahajan, Anubha, Meitinger, Thomas, Metspalu, Andres, Milani, Lili, Momozawa, Yukihide, Morris, Andrew P., Mosley, Thomas H., Jr., Munson, Peter, Murray, Alison D., Nalls, Mike A., Nasri, Ubaydah, Norris, Jill M., North, Kari, Ogunniyi, Adesola, Padmanabhan, Sandosh, Palmas, Walter R., Palmer, Nicholette D., Pankow, James S., Pedersen, Nancy L., Peters, Annette, Peyser, Patricia A., Polasek, Ozren, Raitakari, Olli T., Renström, Frida, Rice, Treva K., Ridker, Paul M., Robino, Antonietta, Robinson, Jennifer G., Rose, Lynda M., Rudan, Igor, Sabanayagam, Charumathi, Salako, Babatunde L., Sandow, Kevin, Schmidt, Carsten O., Schreiner, Pamela J., Scott, William R., Seshadri, Sudha, Sever, Peter, Sitlani, Colleen M., Smith, Jennifer A., Snieder, Harold, Starr, John M., Strauch, Konstantin, Tang, Hua, Taylor, Kent D., Teo, Yik Ying, Tham, Yih Chung, Uitterlinden, André G., Waldenberger, Melanie, Wang, Lihua, Wang, Ya X., Wei, Wen Bin, Williams, Christine, Wilson, Gregory, Wojczynski, Mary K., Yao, Jie, Yuan, Jian-Min, Zonderman, Alan B., Becker, Diane M., Boehnke, Michael, Bowden, Donald W., Chambers, John C., Chen, Yii-Der Ida, de Faire, Ulf, Deary, Ian J., Esko, Tõnu, Farrall, Martin, Forrester, Terrence, Franks, Paul W., Freedman, Barry I., Froguel, Philippe, Gasparini, Paolo, Gieger, Christian, Horta, Bernardo Lessa, Hung, Yi-Jen, Jonas, Jost B., Kato, Norihiro, Kooner, Jaspal S., Laakso, Markku, Lehtimäki, Terho, Liang, Kae-Woei, Magnusson, Patrik K.E., Newman, Anne B., Oldehinkel, Albertine J., Pereira, Alexandre C., Redline, Susan, Rettig, Rainer, Samani, Nilesh J., Scott, James, Shu, Xiao-Ou, van der Harst, Pim, Wagenknecht, Lynne E., Wareham, Nicholas J., Watkins, Hugh, Weir, David R., Wickremasinghe, Ananda R., Wu, Tangchun, Zheng, Wei, Kamatani, Yoichiro, Laurie, Cathy C., Bouchard, Claude, Cooper, Richard S., Evans, Michele K., Gudnason, Vilmundur, Kardia, Sharon L.R., Kritchevsky, Stephen B., Levy, Daniel, O’Connell, Jeff R., Psaty, Bruce M., van Dam, Rob M., Sims, Mario, Arnett, Donna K., Mook-Kanamori, Dennis O., Kelly, Tanika N., Fox, Ervin R., Hayward, Caroline, Fornage, Myriam, Rotimi, Charles N., Province, Michael A., van Duijn, Cornelia M., Tai, E. Shyong, Wong, Tien Yin, Loos, Ruth J.F., Reiner, Alex P., Rotter, Jerome I., Zhu, Xiaofeng, Bierut, Laura J., Gauderman, W. James, Caulfield, Mark J., Elliott, Paul, Rice, Kenneth, Munroe, Patricia B., Morrison, Alanna C., Cupples, L. Adrienne, Rao, Dabeeru C., and Chasman, Daniel I.

Published
2018
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21. Association of lifelong occupation and educational level with subclinical atherosclerosis in different European regions. Results from the IMPROVE study

Author

Tedesco, Calogero C., Veglia, Fabrizio, de Faire, Ulf, Kurl, Sudhir, Smit, Andries J., Rauramaa, Rainer, Giral, Philippe, Amato, Mauro, Bonomi, Alice, Ravani, Alessio, Frigerio, Beatrice, Castelnuovo, Samuela, Sansaro, Daniela, Mannarino, Elmo, Humphries, Steve E., Hamsten, Anders, Tremoli, Elena, and Baldassarre, Damiano

Published
2018
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22. Is There an Association Between Ambient Air Pollution and Bladder Cancer Incidence? Analysis of 15 European Cohorts

Author

Pedersen, Marie, Stafoggia, Massimo, Weinmayr, Gudrun, Andersen, Zorana J., Galassi, Claudia, Sommar, Johan, Forsberg, Bertil, Olsson, David, Oftedal, Bente, Krog, Norun H., Aamodt, Geir, Pyko, Andrei, Pershagen, Göran, Korek, Michal, De Faire, Ulf, Pedersen, Nancy L., Östenson, Claes-Göran, Fratiglioni, Laura, Sørensen, Mette, Eriksen, Kirsten T., Tjønneland, Anne, Peeters, Petra H., Bueno-de-Mesquita, Bas, Vermeulen, Roel, Eeftens, Marloes, Plusquin, Michelle, Key, Timothy J., Jaensch, Andrea, Nagel, Gabriele, Concin, Hans, Wang, Meng, Tsai, Ming-Yi, Grioni, Sara, Marcon, Alessandro, Krogh, Vittorio, Ricceri, Fulvio, Sacerdote, Carlotta, Ranzi, Andrea, Cesaroni, Giulia, Forastiere, Francesco, Tamayo, Ibon, Amiano, Pilar, Dorronsoro, Miren, Stayner, Leslie T., Kogevinas, Manolis, Nieuwenhuijsen, Mark J., Sokhi, Ranjeet, de Hoogh, Kees, Beelen, Rob, Vineis, Paolo, Brunekreef, Bert, Hoek, Gerard, and Raaschou-Nielsen, Ole

Published
2018
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26. Identification of a novel proinsulin-associated SNP and demonstration that proinsulin is unlikely to be a causal factor in subclinical vascular remodelling using Mendelian randomisation

Author

Strawbridge, Rona J., Silveira, Angela, Hoed, Marcel den, Gustafsson, Stefan, Luan, Jian'an, Rybin, Denis, Dupuis, Josée, Li-Gao, Ruifang, Kavousi, Maryam, Dehghan, Abbas, Haljas, Kadri, Lahti, Jari, Gådin, Jesper R., Bäcklund, Alexandra, de Faire, Ulf, Gertow, Karl, Giral, Phillipe, Goel, Anuj, Humphries, Steve E., Kurl, Sudhir, Langenberg, Claudia, Lannfelt, Lars L., Lind, Lars, Lindgren, Cecilia C.M., Mannarino, Elmo, Mook-Kanamori, Dennis O., Morris, Andrew P., de Mutsert, Renée, Rauramaa, Rainer, Saliba-Gustafsson, Peter, Sennblad, Bengt, Smit, Andries J., Syvänen, Ann-Christine, Tremoli, Elena, Veglia, Fabrizio, Zethelius, Björn, Björck, Hanna M., Eriksson, Johan G., Hofman, Albert, Franco, Oscar H., Watkins, Hugh, Jukema, J. Wouter, Florez, Jose C., Wareham, Nicholas J., Meigs, James B., Ingelsson, Erik, Baldassarre, Damiano, and Hamsten, Anders

Published
2017
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27. Carotid plaque-thickness and common carotid IMT show additive value in cardiovascular risk prediction and reclassification

Author

Amato, Mauro, Veglia, Fabrizio, de Faire, Ulf, Giral, Philippe, Rauramaa, Rainer, Smit, Andries J., Kurl, Sudhir, Ravani, Alessio, Frigerio, Beatrice, Sansaro, Daniela, Bonomi, Alice, Tedesco, Calogero C., Castelnuovo, Samuela, Mannarino, Elmo, Humphries, Steve E., Hamsten, Anders, Tremoli, Elena, and Baldassarre, Damiano

Published
2017
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28. Long-term risk of a major cardiovascular event by apoB, apoA-1, and the apoB/apoA-1 ratio-Experience from the Swedish AMORIS cohort: A cohort study

Author

Walldius, Göran, de Faire, Ulf, Alfredsson, Lars, Leander, Karin, Westerholm, Peter, Malmström, Håkan, Ivert, Torbjörn, and Hammar, Niklas

Subjects
Apolipoproteins -- Health aspects -- Measurement, Cardiovascular diseases -- Risk factors -- Patient outcomes, Biological sciences
Abstract

Background Elevated apolipoprotein B (apoB) and elevated apoB/apoA-1 ratio increase the risk of myocardial infarction (MI) and stroke, whereas high apoA-1 is protective. We study how these apolipoproteins are associated with major adverse cardiovascular events (MACEs), whether apoA-1 contributes to this association, and whether abnormal values occur decades before such events develop. Methods and findings In the Swedish AMORIS (Apolipoprotein-related MOrtality RISk) cohort study, 137,100 men and women aged 25-84 years were followed an average 17.8 years. ApoB, apoA-1, and the apoB/apoA-1 ratio were analysed in relation to MACEs (non-fatal MI, stroke, and cardiovascular [CV] mortality), yielding 22,473 events. Hazard ratios (HRs) were estimated using Cox regression. Kaplan-Meier estimates were used to investigate the relationship of MACEs with increasing quintiles of the apoB/apoA-1 ratio in all age groups for both sexes. In nested case-control analyses, cases were randomly matched to age- and sex-matched controls, yielding population trajectories for apolipoproteins. Increased level of apoB and increased apoB/apoA-1 ratio were associated with risk of MACE and all clinical sub-components in both men and women across all ages (10th versus first decile in both sexes combined: HR 1.7 for MACE and 2.7 for non-fatal MI). Decreased values of apoA-1 potentiated the impact of apoB at all levels of apoB (on average across apoB range: 40% increase in HR for MACE and 72% increase in HR for non-fatal MI), indicating that the apoB/apoA-1 ratio covers a broader range of persons with dyslipidaemia at risk than apoB alone. In both men and women, MACEs occurred earlier on average for each increasing quintile of the apoB/apoA-1 ratio. Individuals with the highest levels of apoB/apoA-1 ratio experienced CV events on average several years earlier than those with lower ratios. Higher apoB/apoA-1 ratio in cases of MACE versus controls was seen already about 20 years before the event. A limitation of this study was that adjustment for tobacco smoking and hypertension was only possible in a small validation study. Conclusions An imbalance between apoB and apoA-1 resulting in an increased apoB/apoA-1 ratio is strongly associated with the outcome MACE and its sub-components, in both men and women of all ages. An increased apoB/apoA-1 ratio already 2 decades before events calls for early recognition and primary prevention. Simple evidence-based cut values should be considered in future cardiovascular guidelines., Author(s): Göran Walldius 1,*, Ulf de Faire 1, Lars Alfredsson 1, Karin Leander 1, Peter Westerholm 2, Håkan Malmström 1,3, Torbjörn Ivert 4,5, Niklas Hammar 1,* Introduction Dyslipidaemia is a [...]

Published
2021
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30. PCSK6 Is a Key Protease in the Control of Smooth Muscle Cell Function in Vascular Remodeling

Author

Rykaczewska, Urszula, Suur, Bianca E., Röhl, Samuel, Razuvaev, Anton, Lengquist, Mariette, Sabater-Lleal, Maria, van der Laan, Sander W., Miller, Clint L., Wirka, Robert C., Kronqvist, Malin, Gonzalez Diez, Maria, Vesterlund, Mattias, Gillgren, Peter, Odeberg, Jacob, Lindeman, Jan H., Veglia, Fabrizio, Humphries, Steve E., de Faire, Ulf, Baldassarre, Damiano, Tremoli, Elena, Lehtiö, Janne, Hansson, Göran K., Paulsson-Berne, Gabrielle, Pasterkamp, Gerard, Quertermous, Thomas, Hamsten, Anders, Eriksson, Per, Hedin, Ulf, and Matic, Ljubica

Published
2020
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31. Biomarkers of Dietary Omega-6 Fatty Acids and Incident Cardiovascular Disease and Mortality: An Individual-Level Pooled Analysis of 30 Cohort Studies

Author

Marklund, Matti, Wu, Jason H.Y., Imamura, Fumiaki, Del Gobbo, Liana C., Fretts, Amanda, de Goede, Janette, Shi, Peilin, Tintle, Nathan, Wennberg, Maria, Aslibekyan, Stella, Chen, Tzu-An, de Oliveira Otto, Marcia C., Hirakawa, Yoichiro, Eriksen, Helle Højmark, Kröger, Janine, Laguzzi, Federica, Lankinen, Maria, Murphy, Rachel A., Prem, Kiesha, Samieri, Cécilia, Virtanen, Jyrki, Wood, Alexis C., Wong, Kerry, Yang, Wei-Sin, Zhou, Xia, Baylin, Ana, Boer, Jolanda M.A., Brouwer, Ingeborg A., Campos, Hannia, Chaves, Paulo H. M., Chien, Kuo-Liong, de Faire, Ulf, Djoussé, Luc, Eiriksdottir, Gudny, El-Abbadi, Naglaa, Forouhi, Nita G., Gaziano, J. Michael, Geleijnse, Johanna M., Gigante, Bruna, Giles, Graham, Guallar, Eliseo, Gudnason, Vilmundur, Harris, Tamara, Harris, William S., Helmer, Catherine, Hellenius, Mai-Lis, Hodge, Allison, Hu, Frank B., Jacques, Paul F., Jansson, Jan-Håkan, Kalsbeek, Anya, Khaw, Kay-Tee, Koh, Woon-Puay, Laakso, Markku, Leander, Karin, Lin, Hung-Ju, Lind, Lars, Luben, Robert, Luo, Juhua, McKnight, Barbara, Mursu, Jaakko, Ninomiya, Toshiharu, Overvad, Kim, Psaty, Bruce M., Rimm, Eric, Schulze, Matthias B., Siscovick, David, Skjelbo Nielsen, Michael, Smith, Albert V., Steffen, Brian T., Steffen, Lyn, Sun, Qi, Sundström, Johan, Tsai, Michael Y., Tunstall-Pedoe, Hugh, Uusitupa, Matti I. J., van Dam, Rob M., Veenstra, Jenna, Verschuren, W.M. Monique, Wareham, Nick, Willett, Walter, Woodward, Mark, Yuan, Jian-Min, Micha, Renata, Lemaitre, Rozenn N, Mozaffarian, Dariush, and Risérus, Ulf

Published
2019
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32. Biomarkers of dairy fat intake, incident cardiovascular disease, and all-cause mortality: A cohort study, systematic review, and meta-analysis

Author

Trieu, Kathy, Bhat, Saiuj, Dai, Zhaoli, Leander, Karin, Gigante, Bruna, Qian, Frank, Korat, Andres V. Ardisson, Sun, Qi, Pan, Xiong-Fei, Laguzzi, Federica, Cederholm, Tommy, de Faire, Ulf, Hellénius, Mai-Lis, Wu, Jason H. Y., Risérus, Ulf, and Marklund, Matti

Subjects
Saturated fatty acids -- Health aspects -- Measurement, Dietary fat -- Physiological aspects -- Health aspects, Dairy products -- Nutritional aspects, Cardiovascular diseases -- Risk factors -- Patient outcomes, Biological sciences
Abstract

Background We aimed to investigate the association of serum pentadecanoic acid (15:0), a biomarker of dairy fat intake, with incident cardiovascular disease (CVD) and all-cause mortality in a Swedish cohort study. We also systematically reviewed studies of the association of dairy fat biomarkers (circulating or adipose tissue levels of 15:0, heptadecanoic acid [17:0], and trans-palmitoleic acid [t16:1n-7]) with CVD outcomes or all-cause mortality. Methods and findings We measured 15:0 in serum cholesterol esters at baseline in 4,150 Swedish adults (51% female, median age 60.5 years). During a median follow-up of 16.6 years, 578 incident CVD events and 676 deaths were identified using Swedish registers. In multivariable-adjusted models, higher 15:0 was associated with lower incident CVD risk in a linear dose-response manner (hazard ratio 0.75 per interquintile range; 95% confidence interval 0.61, 0.93, P = 0.009) and nonlinearly with all-cause mortality (P for nonlinearity = 0.03), with a nadir of mortality risk around median 15:0. In meta-analyses including our Swedish cohort and 17 cohort, case-cohort, or nested case-control studies, higher 15:0 and 17:0 but not t16:1n-7 were inversely associated with total CVD, with the relative risk of highest versus lowest tertile being 0.88 (0.78, 0.99), 0.86 (0.79, 0.93), and 1.01 (0.91, 1.12), respectively. Dairy fat biomarkers were not associated with all-cause mortality in meta-analyses, although there were [less than or equal to]3 studies for each biomarker. Study limitations include the inability of the biomarkers to distinguish different types of dairy foods and that most studies in the meta-analyses (including our novel cohort study) only assessed biomarkers at baseline, which may increase the risk of misclassification of exposure levels. Conclusions In a meta-analysis of 18 observational studies including our new cohort study, higher levels of 15:0 and 17:0 were associated with lower CVD risk. Our findings support the need for clinical and experimental studies to elucidate the causality of these relationships and relevant biological mechanisms., Author(s): Kathy Trieu 1, Saiuj Bhat 2, Zhaoli Dai 3,4, Karin Leander 5, Bruna Gigante 6, Frank Qian 7,8, Andres V. Ardisson Korat 9, Qi Sun 7,9, Xiong-Fei Pan 1,10,11, [...]

Published
2021
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33. Genetic loci on chromosome 5 are associated with circulating levels of interleukin-5 and eosinophil count in a European population with high risk for cardiovascular disease

Author

McLeod, Olga, Silveira, Angela, Valdes-Marquez, Elsa, Björkbacka, Harry, Almgren, Peter, Gertow, Karl, Gådin, Jesper R., Bäcklund, Alexandra, Sennblad, Bengt, Baldassarre, Damiano, Veglia, Fabrizio, Humphries, Steve E., Tremoli, Elena, de Faire, Ulf, Nilsson, Jan, Melander, Olle, Hopewell, Jemma C., Clarke, Robert, Björck, Hanna M., Hamsten, Anders, Öhrvik, John, and Strawbridge, Rona J.

Published
2016
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35. Genetic variation in CADM2 as a link between psychological traits and obesity

Author

Morris, Julia, Bailey, Mark E. S., Baldassarre, Damiano, Cullen, Breda, de Faire, Ulf, Ferguson, Amy, Gigante, Bruna, Giral, Philippe, Goel, Anuj, Graham, Nicholas, Hamsten, Anders, Humphries, Steve E., Johnston, Keira J. A., Lyall, Donald M., Lyall, Laura M., Sennblad, Bengt, Silveira, Angela, Smit, Andries J., Tremoli, Elena, Veglia, Fabrizio, Ward, Joey, Watkins, Hugh, Smith, Daniel J., and Strawbridge, Rona J.

Published
2019
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37. Gene-educational attainment interactions in a multi-population genome-wide meta-analysis identify novel lipid loci

Author

de las Fuentes, Lisa, Schwander, Karen L., Brown, Michael R., Bentley, Amy R., Winkler, Thomas W., Sung, Yun Ju, Munroe, Patricia B., Miller, Clint L., Aschard, Hugo, Aslibekyan, Stella, Bartz, Traci M., Bielak, Lawrence F., Chai, Jin Fang, Cheng, Ching Yu, Dorajoo, Rajkumar, Feitosa, Mary F., Guo, Xiuqing, Hartwig, Fernando P., Horimoto, Andrea, Kolčić, Ivana, Lim, Elise, Liu, Yongmei, Manning, Alisa K., Marten, Jonathan, Musani, Solomon K., Noordam, Raymond, Padmanabhan, Sandosh, Rankinen, Tuomo, Richard, Melissa A., Ridker, Paul M., Smith, Albert V., Vojinovic, Dina, Zonderman, Alan B., Alver, Maris, Boissel, Mathilde, Christensen, Kaare, Freedman, Barry I., Gao, Chuan, Giulianini, Franco, Harris, Sarah E., He, Meian, Hsu, Fang Chi, Kühnel, Brigitte, Laguzzi, Federica, Li, Xiaoyin, Lyytikäinen, Leo Pekka, Nolte, Ilja M., Poveda, Alaitz, Rauramaa, Rainer, Riaz, Muhammad, Robino, Antonietta, Sofer, Tamar, Takeuchi, Fumihiko, Tayo, Bamidele O., van der Most, Peter J., Verweij, Niek, Ware, Erin B., Weiss, Stefan, Wen, Wanqing, Yanek, Lisa R., Zhan, Yiqiang, Amin, Najaf, Arking, Dan E., Ballantyne, Christie, Boerwinkle, Eric, Brody, Jennifer A., Broeckel, Ulrich, Campbell, Archie, Canouil, Mickaël, Chai, Xiaoran, Chen, Yii Der Ida, Chen, Xu, Chitrala, Kumaraswamy Naidu, Concas, Maria Pina, de Faire, Ulf, de Mutsert, Renée, de Silva, H. Janaka, de Vries, Paul S., Do, Ahn, Faul, Jessica D., Fisher, Virginia, Floyd, James S., Forrester, Terrence, Friedlander, Yechiel, Girotto, Giorgia, Gu, C. Charles, Hallmans, Göran, Heikkinen, Sami, Heng, Chew Kiat, Homuth, Georg, Hunt, Steven, Ikram, M. Arfan, Jacobs, David R., Kavousi, Maryam, Khor, Chiea Chuen, Kilpeläinen, Tuomas O., Koh, Woon Puay, Komulainen, Pirjo, Langefeld, Carl D., Liang, Jingjing, Liu, Kiang, Liu, Jianjun, Lohman, Kurt, Mägi, Reedik, Manichaikul, Ani W., McKenzie, Colin A., Meitinger, Thomas, Milaneschi, Yuri, Nauck, Matthias, Nelson, Christopher P., O’Connell, Jeffrey R., Palmer, Nicholette D., Pereira, Alexandre C., Perls, Thomas, Peters, Annette, Polašek, Ozren, Raitakari, Olli T., Rice, Kenneth, Rice, Treva K., Rich, Stephen S., Sabanayagam, Charumathi, Schreiner, Pamela J., Shu, Xiao Ou, Sidney, Stephen, Sims, Mario, Smith, Jennifer A., Starr, John M., Strauch, Konstantin, Tai, E. Shyong, Taylor, Kent D., Tsai, Michael Y., Uitterlinden, André G., van Heemst, Diana, Waldenberger, Melanie, Wang, Ya Xing, Wei, Wen Bin, Wilson, Gregory, Xuan, Deng, Yao, Jie, Yu, Caizheng, Yuan, Jian Min, Zhao, Wei, Becker, Diane M., Bonnefond, Amélie, Bowden, Donald W., Cooper, Richard S., Deary, Ian J., Divers, Jasmin, Esko, Tõnu, Franks, Paul W., Froguel, Philippe, Gieger, Christian, Jonas, Jost B., Kato, Norihiro, Lakka, Timo A., Leander, Karin, Lehtimäki, Terho, Magnusson, Patrik K.E., North, Kari E., Ntalla, Ioanna, Penninx, Brenda, Samani, Nilesh J., Snieder, Harold, Spedicati, Beatrice, van der Harst, Pim, Völzke, Henry, Wagenknecht, Lynne E., Weir, David R., Wojczynski, Mary K., Wu, Tangchun, Zheng, Wei, Zhu, Xiaofeng, Bouchard, Claude, Chasman, Daniel I., Evans, Michele K., Fox, Ervin R., Gudnason, Vilmundur, Hayward, Caroline, Horta, Bernardo L., Kardia, Sharon L.R., Krieger, Jose Eduardo, Mook-Kanamori, Dennis O., Peyser, Patricia A., Province, Michael M., Psaty, Bruce M., Rudan, Igor, Sim, Xueling, Smith, Blair H., van Dam, Rob M., van Duijn, Cornelia M., Wong, Tien Yin, Arnett, Donna K., Rao, Dabeeru C., Gauderman, James, Liu, Ching Ti, Morrison, Alanna C., Rotter, Jerome I., Fornage, Myriam, de las Fuentes, Lisa, Schwander, Karen L., Brown, Michael R., Bentley, Amy R., Winkler, Thomas W., Sung, Yun Ju, Munroe, Patricia B., Miller, Clint L., Aschard, Hugo, Aslibekyan, Stella, Bartz, Traci M., Bielak, Lawrence F., Chai, Jin Fang, Cheng, Ching Yu, Dorajoo, Rajkumar, Feitosa, Mary F., Guo, Xiuqing, Hartwig, Fernando P., Horimoto, Andrea, Kolčić, Ivana, Lim, Elise, Liu, Yongmei, Manning, Alisa K., Marten, Jonathan, Musani, Solomon K., Noordam, Raymond, Padmanabhan, Sandosh, Rankinen, Tuomo, Richard, Melissa A., Ridker, Paul M., Smith, Albert V., Vojinovic, Dina, Zonderman, Alan B., Alver, Maris, Boissel, Mathilde, Christensen, Kaare, Freedman, Barry I., Gao, Chuan, Giulianini, Franco, Harris, Sarah E., He, Meian, Hsu, Fang Chi, Kühnel, Brigitte, Laguzzi, Federica, Li, Xiaoyin, Lyytikäinen, Leo Pekka, Nolte, Ilja M., Poveda, Alaitz, Rauramaa, Rainer, Riaz, Muhammad, Robino, Antonietta, Sofer, Tamar, Takeuchi, Fumihiko, Tayo, Bamidele O., van der Most, Peter J., Verweij, Niek, Ware, Erin B., Weiss, Stefan, Wen, Wanqing, Yanek, Lisa R., Zhan, Yiqiang, Amin, Najaf, Arking, Dan E., Ballantyne, Christie, Boerwinkle, Eric, Brody, Jennifer A., Broeckel, Ulrich, Campbell, Archie, Canouil, Mickaël, Chai, Xiaoran, Chen, Yii Der Ida, Chen, Xu, Chitrala, Kumaraswamy Naidu, Concas, Maria Pina, de Faire, Ulf, de Mutsert, Renée, de Silva, H. Janaka, de Vries, Paul S., Do, Ahn, Faul, Jessica D., Fisher, Virginia, Floyd, James S., Forrester, Terrence, Friedlander, Yechiel, Girotto, Giorgia, Gu, C. Charles, Hallmans, Göran, Heikkinen, Sami, Heng, Chew Kiat, Homuth, Georg, Hunt, Steven, Ikram, M. Arfan, Jacobs, David R., Kavousi, Maryam, Khor, Chiea Chuen, Kilpeläinen, Tuomas O., Koh, Woon Puay, Komulainen, Pirjo, Langefeld, Carl D., Liang, Jingjing, Liu, Kiang, Liu, Jianjun, Lohman, Kurt, Mägi, Reedik, Manichaikul, Ani W., McKenzie, Colin A., Meitinger, Thomas, Milaneschi, Yuri, Nauck, Matthias, Nelson, Christopher P., O’Connell, Jeffrey R., Palmer, Nicholette D., Pereira, Alexandre C., Perls, Thomas, Peters, Annette, Polašek, Ozren, Raitakari, Olli T., Rice, Kenneth, Rice, Treva K., Rich, Stephen S., Sabanayagam, Charumathi, Schreiner, Pamela J., Shu, Xiao Ou, Sidney, Stephen, Sims, Mario, Smith, Jennifer A., Starr, John M., Strauch, Konstantin, Tai, E. Shyong, Taylor, Kent D., Tsai, Michael Y., Uitterlinden, André G., van Heemst, Diana, Waldenberger, Melanie, Wang, Ya Xing, Wei, Wen Bin, Wilson, Gregory, Xuan, Deng, Yao, Jie, Yu, Caizheng, Yuan, Jian Min, Zhao, Wei, Becker, Diane M., Bonnefond, Amélie, Bowden, Donald W., Cooper, Richard S., Deary, Ian J., Divers, Jasmin, Esko, Tõnu, Franks, Paul W., Froguel, Philippe, Gieger, Christian, Jonas, Jost B., Kato, Norihiro, Lakka, Timo A., Leander, Karin, Lehtimäki, Terho, Magnusson, Patrik K.E., North, Kari E., Ntalla, Ioanna, Penninx, Brenda, Samani, Nilesh J., Snieder, Harold, Spedicati, Beatrice, van der Harst, Pim, Völzke, Henry, Wagenknecht, Lynne E., Weir, David R., Wojczynski, Mary K., Wu, Tangchun, Zheng, Wei, Zhu, Xiaofeng, Bouchard, Claude, Chasman, Daniel I., Evans, Michele K., Fox, Ervin R., Gudnason, Vilmundur, Hayward, Caroline, Horta, Bernardo L., Kardia, Sharon L.R., Krieger, Jose Eduardo, Mook-Kanamori, Dennis O., Peyser, Patricia A., Province, Michael M., Psaty, Bruce M., Rudan, Igor, Sim, Xueling, Smith, Blair H., van Dam, Rob M., van Duijn, Cornelia M., Wong, Tien Yin, Arnett, Donna K., Rao, Dabeeru C., Gauderman, James, Liu, Ching Ti, Morrison, Alanna C., Rotter, Jerome I., and Fornage, Myriam

Abstract

Introduction: Educational attainment, widely used in epidemiologic studies as a surrogate for socioeconomic status, is a predictor of cardiovascular health outcomes. Methods:A two-stage genome-wide meta-analysis of low-density lipoprotein cholesterol (LDL), high-density lipoprotein cholesterol (HDL), and triglyceride (TG) levels was performed while accounting for gene-educational attainment interactions in up to 226,315 individuals from five population groups. We considered two educational attainment variables: “Some College” (yes/no, for any education beyond high school) and “Graduated College” (yes/no, for completing a 4-year college degree). Genome-wide significant (p < 5 × 10−8) and suggestive (p < 1 × 10−6) variants were identified in Stage 1 (in up to 108,784 individuals) through genome-wide analysis, and those variants were followed up in Stage 2 studies (in up to 117,531 individuals). Results: In combined analysis of Stages 1 and 2, we identified 18 novel lipid loci (nine for LDL, seven for HDL, and two for TG) by two degree-of-freedom (2 DF) joint tests of main and interaction effects. Four loci showed significant interaction with educational attainment. Two loci were significant only in cross-population analyses. Several loci include genes with known or suggested roles in adipose (FOXP1, MBOAT4, SKP2, STIM1, STX4), brain (BRI3, FILIP1, FOXP1, LINC00290, LMTK2, MBOAT4, MYO6, SENP6, SRGAP3, STIM1, TMEM167A, TMEM30A), and liver (BRI3, FOXP1) biology, highlighting the potential importance of brain-adipose-liver communication in the regulation of lipid metabolism. An investigation of the potential druggability of genes in identified loci resulted in five gene targets shown to interact with drugs approved by the Food and Drug Administration, including genes with roles in adipose and brain tissue.Discussion: Genome-wide interaction analysis of educational a

Published
2023

38. Long-term effects of elemental composition of particulate matter on inflammatory blood markers in European cohorts

Author

Hampel, Regina, Peters, Annette, Beelen, Rob, Brunekreef, Bert, Cyrys, Josef, de Faire, Ulf, de Hoogh, Kees, Fuks, Kateryna, Hoffmann, Barbara, Hüls, Anke, Imboden, Medea, Jedynska, Aleksandra, Kooter, Ingeborg, Koenig, Wolfgang, Künzli, Nino, Leander, Karin, Magnusson, Patrik, Männistö, Satu, Penell, Johanna, Pershagen, Göran, Phuleria, Harish, Probst-Hensch, Nicole, Pundt, Noreen, Schaffner, Emmanuel, Schikowski, Tamara, Sugiri, Dorothea, Tiittanen, Pekka, Tsai, Ming-Yi, Wang, Meng, Wolf, Kathrin, and Lanki, Timo

Published
2015
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41. GWAS-identified loci for coronary heart disease are associated with intima-media thickness and plaque presence at the carotid artery bulb

Author

den Hoed, Marcel, Strawbridge, Rona J., Almgren, Peter, Gustafsson, Stefan, Axelsson, Tomas, Engström, Gunnar, de Faire, Ulf, Hedblad, Bo, Humphries, Steve E., Lindgren, Cecilia M., Morris, Andrew P., Östling, Gerd, Syvänen, Ann-Christine, Tremoli, Elena, Hamsten, Anders, Ingelsson, Erik, Melander, Olle, and Lind, Lars

Published
2015
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42. Plasma IL-5 concentration and subclinical carotid atherosclerosis

Author

Silveira, Angela, McLeod, Olga, Strawbridge, Rona J., Gertow, Karl, Sennblad, Bengt, Baldassarre, Damiano, Veglia, Fabrizio, Deleskog, Anna, Persson, Jonas, Leander, Karin, Gigante, Bruna, Kauhanen, Jussi, Rauramaa, Rainer, Smit, Andries J., Mannarino, Elmo, Giral, Philippe, Gustafsson, Sven, Söderberg, Stefan, Öhrvik, John, Humphries, Steve E., Tremoli, Elena, de Faire, Ulf, and Hamsten, Anders

Published
2015
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43. Cross-Sectional Gene-Smoking Interaction Analysis in Relation to Subclinical Atherosclerosis-Results From the IMPROVE Study

Author

Maitusong, Buamina, Laguzzi, Federica, Strawbridge, Rona J, Baldassarre, Damiano, Veglia, Fabrizio, Humphries, Steve E, Savonen, Kai, Kurl, Sudhir, Pirro, Matteo, Smit, Andries J, Giral, Philippe, Silveira, Angela, Tremoli, Elena, Hamsten, Anders, de Faire, Ulf, Gigante, Bruna, and Leander, Karin

Subjects
cardiovascular disease, carotid intima-media thickness, infarction, atherosclerosis, sample size
Published
2023

45. Low levels of IgM antibodies against phosphorylcholine are associated with fast carotid intima media thickness progression and cardiovascular risk in men

Author

Gigante, Bruna, Leander, Karin, Vikström, Max, Baldassarre, Damiano, Veglia, Fabrizio, Strawbridge, Rona J., McLeod, Olga, Gertow, Karl, Sennblad, Bengt, Shah, Sonia, Zabaneh, Delilah, Humphries, Steve E., Kauhanen, Jussi, Rauramaa, Rainer, Smit, Andries J., Mannarino, Elmo, Giral, Philippe, Tremoli, Elena, Hamsten, Anders, Frostegård, Johan, and de Faire, Ulf

Published
2014
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46. Long-term exposure to elemental constituents of particulate matter and cardiovascular mortality in 19 European cohorts: Results from the ESCAPE and TRANSPHORM projects

Author

Wang, Meng, Beelen, Rob, Stafoggia, Massimo, Raaschou-Nielsen, Ole, Andersen, Zorana Jovanovic, Hoffmann, Barbara, Fischer, Paul, Houthuijs, Danny, Nieuwenhuijsen, Mark, Weinmayr, Gudrun, Vineis, Paolo, Xun, Wei W., Dimakopoulou, Konstantina, Samoli, Evangelia, Laatikainen, Tiina, Lanki, Timo, Turunen, Anu W., Oftedal, Bente, Schwarze, Per, Aamodt, Geir, Penell, Johanna, De Faire, Ulf, Korek, Michal, Leander, Karin, Pershagen, Göran, Pedersen, Nancy L., Östenson, Claes-Göran, Fratiglioni, Laura, Eriksen, Kirsten Thorup, Sørensen, Mette, Tjønneland, Anne, Bueno-de-Mesquita, Bas, Eeftens, Marloes, Bots, Michiel L., Meliefste, Kees, Krämer, Ursula, Heinrich, Joachim, Sugiri, Dorothea, Key, Timothy, de Hoogh, Kees, Wolf, Kathrin, Peters, Annette, Cyrys, Josef, Jaensch, Andrea, Concin, Hans, Nagel, Gabriele, Tsai, Ming-Yi, Phuleria, Harish, Ineichen, Alex, Künzli, Nino, Probst-Hensch, Nicole, Schaffner, Emmanuel, Vilier, Alice, Clavel-Chapelon, Françoise, Declerq, Christophe, Ricceri, Fulvio, Sacerdote, Carlotta, Marcon, Alessandro, Galassi, Claudia, Migliore, Enrica, Ranzi, Andrea, Cesaroni, Giulia, Badaloni, Chiara, Forastiere, Francesco, Katsoulis, Michail, Trichopoulou, Antonia, Keuken, Menno, Jedynska, Aleksandra, Kooter, Ingeborg M., Kukkonen, Jaakko, Sokhi, Ranjeet S., Brunekreef, Bert, Katsouyanni, Klea, and Hoek, Gerard

Published
2014
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48. Effects of long-term exposure to air pollution on natural-cause mortality: an analysis of 22 European cohorts within the multicentre ESCAPE project

Author

Beelen, Rob, Raaschou-Nielsen, Ole, Stafoggia, Massimo, Andersen, Zorana Jovanovic, Weinmayr, Gudrun, Hoffmann, Barbara, Wolf, Kathrin, Samoli, Evangelia, Fischer, Paul, Nieuwenhuijsen, Mark, Vineis, Paolo, Xun, Wei W, Katsouyanni, Klea, Dimakopoulou, Konstantina, Oudin, Anna, Forsberg, Bertil, Modig, Lars, Havulinna, Aki S, Lanki, Timo, Turunen, Anu, Oftedal, Bente, Nystad, Wenche, Nafstad, Per, De Faire, Ulf, Pedersen, Nancy L, Östenson, Claes-Göran, Fratiglioni, Laura, Penell, Johanna, Korek, Michal, Pershagen, Göran, Eriksen, Kirsten Thorup, Overvad, Kim, Ellermann, Thomas, Eeftens, Marloes, Peeters, Petra H, Meliefste, Kees, Wang, Meng, Bueno-de-Mesquita, Bas, Sugiri, Dorothea, Krämer, Ursula, Heinrich, Joachim, de Hoogh, Kees, Key, Timothy, Peters, Annette, Hampel, Regina, Concin, Hans, Nagel, Gabriele, Ineichen, Alex, Schaffner, Emmanuel, Probst-Hensch, Nicole, Künzli, Nino, Schindler, Christian, Schikowski, Tamara, Adam, Martin, Phuleria, Harish, Vilier, Alice, Clavel-Chapelon, Françoise, Declercq, Christophe, Grioni, Sara, Krogh, Vittorio, Tsai, Ming-Yi, Ricceri, Fulvio, Sacerdote, Carlotta, Galassi, Claudia, Migliore, Enrica, Ranzi, Andrea, Cesaroni, Giulia, Badaloni, Chiara, Forastiere, Francesco, Tamayo, Ibon, Amiano, Pilar, Dorronsoro, Miren, Katsoulis, Michail, Trichopoulou, Antonia, Brunekreef, Bert, and Hoek, Gerard

Published
2014
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49. Long-term Exposure to Air Pollution and Cardiovascular Mortality: An Analysis of 22 European Cohorts

Author

Beelen, Rob, Stafoggia, Massimo, Raaschou-Nielsen, Ole, Andersen, Zorana Jovanovic, Xun, Wei W., Katsouyanni, Klea, Dimakopoulou, Konstantina, Brunekreef, Bert, Weinmayr, Gudrun, Hoffmann, Barbara, Wolf, Kathrin, Samoli, Evangelia, Houthuijs, Danny, Nieuwenhuijsen, Mark, Oudin, Anna, Forsberg, Bertil, Olsson, David, Salomaa, Veikko, Lanki, Timo, Yli-Tuomi, Tarja, Oftedal, Bente, Aamodt, Geir, Nafstad, Per, De Faire, Ulf, Pedersen, Nancy L., Östenson, Claes-Göran, Fratiglioni, Laura, Penell, Johanna, Korek, Michal, Pyko, Andrei, Eriksen, Kirsten Thorup, Tjønneland, Anne, Becker, Thomas, Eeftens, Marloes, Bots, Michiel, Meliefste, Kees, Wang, Meng, Bueno-de-Mesquita, Bas, Sugiri, Dorothea, Krämer, Ursula, Heinrich, Joachim, de Hoogh, Kees, Key, Timothy, Peters, Annette, Cyrys, Josef, Concin, Hans, Nagel, Gabriele, Ineichen, Alex, Schaffner, Emmanuel, Probst-Hensch, Nicole, Dratva, Julia, Ducret-Stich, Regina, Vilier, Alice, Clavel-Chapelon, Françoise, Stempfelet, Morgane, Grioni, Sara, Krogh, Vittorio, Tsai, Ming-Yi, Marcon, Alessandro, Ricceri, Fulvio, Sacerdote, Carlotta, Galassi, Claudia, Migliore, Enrica, Ranzi, Andrea, Cesaroni, Giulia, Badaloni, Chiara, Forastiere, Francesco, Tamayo, Ibon, Amiano, Pilar, Dorronsoro, Miren, Katsoulis, Michail, Trichopoulou, Antonia, Vineis, Paolo, and Hoek, Gerard

Published
2014

50. Plasma autoantibodies against apolipoprotein B-100 peptide 210 in subclinical atherosclerosis

Author

McLeod, Olga, Silveira, Angela, Fredrikson, Gunilla N., Gertow, Karl, Baldassarre, Damiano, Veglia, Fabrizio, Sennblad, Bengt, Strawbridge, Rona J., Larsson, Malin, Leander, Karin, Gigante, Bruna, Kauhanen, Jussi, Rauramaa, Rainer, Smit, Andries J., Mannarino, Elmo, Giral, Philippe, Humphries, Steve E., Tremoli, Elena, de Faire, Ulf, Öhrvik, John, Nilsson, Jan, and Hamsten, Anders

Published
2014
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