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2. Genome-wide association study and functional characterization identifies candidate genes for insulin-stimulated glucose uptake

Author

Williamson, Alice, Norris, Dougall M., Yin, Xianyong, Broadaway, K. Alaine, Moxley, Anne H., Vadlamudi, Swarooparani, Wilson, Emma P., Jackson, Anne U., Ahuja, Vasudha, Andersen, Mette K., Arzumanyan, Zorayr, Bonnycastle, Lori L., Bornstein, Stefan R., Bretschneider, Maxi P., Buchanan, Thomas A., Chang, Yi-Cheng, Chuang, Lee-Ming, Chung, Ren-Hua, Clausen, Tine D., Damm, Peter, Delgado, Graciela E., de Mello, Vanessa D., Dupuis, Josée, Dwivedi, Om P., Erdos, Michael R., Silva, Lilian Fernandes, Frayling, Timothy M., Gieger, Christian, Goodarzi, Mark O., Guo, Xiuqing, Gustafsson, Stefan, Hakaste, Liisa, Hammar, Ulf, Hatem, Gad, Herrmann, Sandra, Højlund, Kurt, Horn, Katrin, Hsueh, Willa A., Hung, Yi-Jen, Hwu, Chii-Min, Jonsson, Anna, Kårhus, Line L., Kleber, Marcus E., Kovacs, Peter, Lakka, Timo A., Lauzon, Marie, Lee, I-Te, Lindgren, Cecilia M., Lindström, Jaana, Linneberg, Allan, Liu, Ching-Ti, Luan, Jian’an, Aly, Dina Mansour, Mathiesen, Elisabeth, Moissl, Angela P., Morris, Andrew P., Narisu, Narisu, Perakakis, Nikolaos, Peters, Annette, Prasad, Rashmi B., Rodionov, Roman N., Roll, Kathryn, Rundsten, Carsten F., Sarnowski, Chloé, Savonen, Kai, Scholz, Markus, Sharma, Sapna, Stinson, Sara E., Suleman, Sufyan, Tan, Jingyi, Taylor, Kent D., Uusitupa, Matti, Vistisen, Dorte, Witte, Daniel R., Walther, Romy, Wu, Peitao, Xiang, Anny H., Zethelius, Björn, Ahlqvist, Emma, Bergman, Richard N., Chen, Yii-Der Ida, Collins, Francis S., Fall, Tove, Florez, Jose C., Fritsche, Andreas, Grallert, Harald, Groop, Leif, Hansen, Torben, Koistinen, Heikki A., Komulainen, Pirjo, Laakso, Markku, Lind, Lars, Loeffler, Markus, März, Winfried, Meigs, James B., Raffel, Leslie J., Rauramaa, Rainer, Rotter, Jerome I., Schwarz, Peter E. H., Stumvoll, Michael, Sundström, Johan, Tönjes, Anke, Tuomi, Tiinamaija, Tuomilehto, Jaakko, Wagner, Robert, Barroso, Inês, Walker, Mark, Grarup, Niels, Boehnke, Michael, Wareham, Nicholas J., Mohlke, Karen L., Wheeler, Eleanor, O’Rahilly, Stephen, Fazakerley, Daniel J., and Langenberg, Claudia

Published
2023
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4. 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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19. A temporary regulation to manage an impending shortage due to extraordinary prescribing patterns of chloroquines observed during early phase of COVID-19 epidemic.

Author

Kälkner, Karl-Mikael, Sundström, Anders, Haverinen, Maria Juhasz, Nordback, Kenneth, Arthurson, Veronica, Zethelius, Björn, and Ljung, Rickard

Subjects
COVID-19 pandemic, COVID-19 treatment, SCARCITY, CHLOROQUINE, HYDROXYCHLOROQUINE
Abstract

Background: Chloroquine and hydroxychloroquine (C/HC) received considerable international media attention due to anticipated treatment effect in COVID-19. This led to increased prescriptions threatening to generate product shortages for patients prescribed within approved indications. We evaluated effects of a temporary regulation mandating pharmacies to only dispense C/HC prescribed by physicians with defined specialties. Methods: Data from Region Stockholm, which include 2.4 out of 10 million Sweden's population, were used. Weekly time trends of prescriptions and requisitions of C/HC by prescriber's workplace during January to April 2020 were followed. Results: Numbers of unique individuals with filled prescriptions of chloroquine increased tenfold and of hydroxychloroquine more than threefold from January to March. In the first week of April, filled prescriptions of C/HC dropped. In the later weeks of April, the number of filled prescriptions was back at similar levels as before the SARS-CoV-2 outbreak. During January and February, specialists in rheumatology accounted for 686 out of all 979 prescriptions dispensed (70.1%) of C/HC. In March, a large proportion of prescriptions dispensed were from specialists not usually prescribing C/HC, and rheumatology accounted for 628 out of all 1,639 prescriptions (38.3%). In April, specialists in rheumatology accounted for 386 out of all 641 prescriptions dispensed (60.0%). Conclusion: After an observed increase in prescriptions of C/HC, a temporary regulation was introduced on 2nd April 2020 to reduce prescriptions from specialists not usually prescribing C/HC to avoid shortages for patients within approved indications. Subsequently, dispensed prescriptions decreased from April and remained at pre-COVID-19 levels thereafter. [ABSTRACT FROM AUTHOR]

Published
2023
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20. Validation of myocarditis diagnoses in the Swedish patient register for analyses of potential adverse reactions to COVID-19 vaccines.

Author

Gedeborg, Rolf, Holm, Lennart, Feltelius, Nils, Sundström, Anders, Eggers, Kai M., Nurminen, Marja-Leena, Grünewald, Maria, Pihlström, Nicklas, Zethelius, Björn, and Ljung, Rickard

Subjects
VACCINATION complications, MYOCARDITIS, COVID-19, MAGNETIC resonance imaging, DIAGNOSIS
Abstract

Background: Coronavirus disease 2019 (COVID-19) mRNA vaccines are associated with an increased risk of myocarditis using hospital discharge diagnoses as an outcome. The validity of these register-based diagnoses is uncertain. Methods: Patient records for subjects < 40 years of age and a diagnosis of myocarditis in the Swedish National Patient Register were manually reviewed. Brighton Collaboration diagnosis criteria for myocarditis were applied based on patient history, clinical examination, laboratory data, electrocardiograms, echocardiography, magnetic resonance imaging and myocardial biopsy. Poisson regression was used to estimate incidence rate ratios, comparing the register-based outcome variable to validated outcomes. Interrater reliability was assessed by a blinded re-evaluation. Results: Overall, 95.6% (327/342) of cases registered as myocarditis were confirmed (definite, probable or possible myocarditis according to Brighton Collaboration diagnosis criteria, positive predictive value 0.96 [95% CI 0.93-0.98]). Of the 4.4% (15/342) cases reclassified as no myocarditis or as insufficient information, two cases had been exposed to the COVID-19 vaccine no more than 28 days before the myocarditis diagnosis, two cases were exposed >28 days before admission and 11 cases were unexposed to the vaccine. The reclassification had only minor impact on incidence rate ratios for myocarditis following COVID-19 vaccination. In total, 51 cases were sampled for a blinded re-evaluation. Of the 30 randomly sampled cases initially classified as either definite or probably myocarditis, none were re-classified after re-evaluation. Of the in all 15 cases initially classified as no myocarditis or insufficient information, 7 were after re-evaluation re-classified as probable or possible myocarditis. This re-classification was mostly due to substantial variability in electrocardiogram interpretation. Conclusion: This validation of register-based diagnoses of myocarditis by manual patient record review confirmed the register diagnosis in 96% of cases and had high interrater reliability. Reclassification had only a minor impact on the incidence rate ratios for myocarditis following COVID-19 vaccination. [ABSTRACT FROM AUTHOR]

Published
2023
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31. Self-reported physical activity and different cardiovascular diseases—Results from updated measurements over 40 years.

Author

Lind, Lars, Zethelius, Björn, and Byberg, Liisa

Subjects
*PHYSICAL activity, *CARDIOVASCULAR diseases, *MYOCARDIAL infarction, *ISCHEMIC stroke, *HEART failure, *DRUG-eluting stents
Abstract

Background: Self-reported leisure-time physical activity (PA) has previously been linked to risk of cardiovascular disease (CVD). We now aim to investigate the strength of associations between PA and different CVDs and how the risk varies with age. Methods: PA and traditional CV risk factors assessed by a questionnaire on a four-level scale in 2,175 men at age 50 years in the ULSAM study. Examinations were thereafter repeated at ages 60, 70, and 77. Results: During 40 years follow-up, 883 individuals experienced a CVD (myocardial infarction, stroke, or heart failure). Using data from all four examinations, a graded reduction in risk of incident CVD was seen with increasing PA (HR 0.84, 95%CI; 0.77–0.93, p = 0.001 for trend test). PA was related to myocardial infarction (HR 0.84, 95%CI; 0.74–0.95, 490 cases), heart failure (HR 0.79, 95%CI; 0.68–0.91, 356 cases), but only of borderline significance vs ischemic stroke (HR 0.85, 95%CI; 0.73–1.00, 315 cases) when the CVDs were analyzed separately. Adjusting for traditional CV risk factors attenuated all relationships between PA and incident CVD, and PA did not improve discrimination of CVD when added on top of risk factors. When 10-year risk was calculated from each examination, age 70 was the time-point when PA was most closely related to incident CVD. Conclusion: Leisure-time physical activity is related to future CVD. This was most evident at 70 years of age. If a causal relationship between self-reported PA and CVD exists, this relationship might to a major degree be mediated by traditional risk factors. [ABSTRACT FROM AUTHOR]

Published
2022
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34. Genome-Wide Association Identifies Nine Common Variants Associated With Fasting Proinsulin Levels and Provides New Insights Into the Pathophysiology of Type 2 Diabetes

Author

Strawbridge, Rona J., Dupuis, Josée, Prokopenko, Inga, Barker, Adam, Ahlqvist, Emma, Rybin, Denis, Petrie, John R., Travers, Mary E., Bouatia-Naji, Nabila, Dimas, Antigone S., Nica, Alexandra, Wheeler, Eleanor, Chen, Han, Voight, Benjamin F., Taneera, Jalal, Kanoni, Stavroula, Peden, John F., Turrini, Fabiola, Gustafsson, Stefan, Zabena, Carina, Almgren, Peter, Barker, David J.P., Barnes, Daniel, Dennison, Elaine M., Eriksson, Johan G., Eriksson, Per, Eury, Elodie, Folkersen, Lasse, Fox, Caroline S., Frayling, Timothy M., Goel, Anuj, Gu, Harvest F., Horikoshi, Momoko, Isomaa, Bo, Jackson, Anne U., Jameson, Karen A., Kajantie, Eero, Kerr-Conte, Julie, Kuulasmaa, Teemu, Kuusisto, Johanna, Loos, Ruth J.F., Luan, Jianʼan, Makrilakis, Konstantinos, Manning, Alisa K., Martínez-Larrad, María Teresa, Narisu, Narisu, Nastase Mannila, Maria, Öhrvik, John, Osmond, Clive, Pascoe, Laura, Payne, Felicity, Sayer, Avan A., Sennblad, Bengt, Silveira, Angela, Stančáková, Alena, Stirrups, Kathy, Swift, Amy J., Syvänen, Ann-Christine, Tuomi, Tiinamaija, van ʼt Hooft, Ferdinand M., Walker, Mark, Weedon, Michael N., Xie, Weijia, Zethelius, Björn, Ongen, Halit, Mälarstig, Anders, Hopewell, Jemma C., Saleheen, Danish, Chambers, John, Parish, Sarah, Danesh, John, Kooner, Jaspal, Östenson, Claes-Göran, Lind, Lars, Cooper, Cyrus C., Serrano-Ríos, Manuel, Ferrannini, Ele, Forsen, Tom J., Clarke, Robert, Franzosi, Maria Grazia, Seedorf, Udo, Watkins, Hugh, Froguel, Philippe, Johnson, Paul, Deloukas, Panos, Collins, Francis S., Laakso, Markku, Dermitzakis, Emmanouil T., Boehnke, Michael, McCarthy, Mark I., Wareham, Nicholas J., Groop, Leif, Pattou, François, Gloyn, Anna L., Dedoussis, George V., Lyssenko, Valeriya, Meigs, James B., Barroso, Inês, Watanabe, Richard M., Ingelsson, Erik, Langenberg, Claudia, Hamsten, Anders, and Florez, Jose C.

Published
2011
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39. Detailed Physiologic Characterization Reveals Diverse Mechanisms for Novel Genetic Loci Regulating Glucose and Insulin Metabolism in Humans

Author

Ingelsson, Erik, Langenberg, Claudia, Hivert, Marie-France, Prokopenko, Inga, Lyssenko, Valeriya, Dupuis, Josée, Mägi, Reedik, Sharp, Stephen, Jackson, Anne U., Assimes, Themistocles L., Shrader, Peter, Knowles, Joshua W., Zethelius, Björn, Abbasi, Fahim A., Bergman, Richard N., Bergmann, Antje, Berne, Christian, Boehnke, Michael, Bonnycastle, Lori L., Bornstein, Stefan R., Buchanan, Thomas A., Bumpstead, Suzannah J., Böttcher, Yvonne, Chines, Peter, Collins, Francis S., Cooper, Cyrus C., Dennison, Elaine M., Erdos, Michael R., Ferrannini, Ele, Fox, Caroline S., Graessler, Jürgen, Hao, Ke, Isomaa, Bo, Jameson, Karen A., Kovacs, Peter, Kuusisto, Johanna, Laakso, Markku, Ladenvall, Claes, Mohlke, Karen L., Morken, Mario A., Narisu, Narisu, Nathan, David M., Pascoe, Laura, Payne, Felicity, Petrie, John R., Sayer, Avan A., Schwarz, Peter E., Scott, Laura J., Stringham, Heather M., Stumvoll, Michael, Swift, Amy J., Syvänen, Ann-Christine, Tuomi, Tiinamaija, Tuomilehto, Jaakko, Tönjes, Anke, Valle, Timo T., Williams, Gordon H., Lind, Lars, Barroso, Inês, Quertermous, Thomas, Walker, Mark, Wareham, Nicholas J., Meigs, James B., McCarthy, Mark I., Groop, Leif, Watanabe, Richard M., and Florez, Jose C.

Published
2010
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45. Comparison of years of life lost to 1,565 suicides versus 10,650 COVID-19 deaths in 2020 in Sweden: four times more years of life lost per suicide than per COVID-19 death.

Author

Ljung, Rickard, Grünewald, Maria, Sundström, Anders, Sundbom, Lena Thunander, and Zethelius, Björn

Subjects
SARS-CoV-2, SUICIDE
Abstract

Background: The burden of disease from the severe acute respiratory syndrome coronavirus 2 (SARSCoV-2) pandemic is large; however, suicide affects the population year after year. From a public health perspective, it is important to not neglect contributors to the total burden of disease. The aim of this paper is to compare years of life lost (YLL) to suicide with those lost to coronavirus disease 2019 (COVID-19). Methods: A nationwide cohort study in 2020, in Sweden. YLL was measured as the sex- and age-specific remaining life expectancy at the time of the person's death based on the death risks that pertained to the Swedish population in 2019. YLL to suicide was compared to YLL to COVID-19 and presented by sex and age groups. Suicide deaths in 2020 were estimated as the annual average of suicides in 2015-2019. Results: Annual average of suicide was 1,565, whereof 1,076 (68.8%) men and 489 (31.2%) women. In 2020, 10,650 persons died of COVID-19, whereof 5,681 (53.3%) men and 4,969 (46.7%) women. Estimated total YLL to suicide and COVID-19 in 2020 was 53,237 and 90,116, respectively. The COVID-19 YLL to suicide YLL ratio in 2020 was 1.69 (90,116/53,237). Men accounted for 67.1% of suicide YLL and of 56.4% of COVID-19 YLL. Those 44 years or younger accounted for 60.3% of suicide YLL and 3.9% of COVID-19 YLL. Those 75 years and older accounted for 2.9% of suicide YLL and 60.9% of COVID-19 YLL. On average, each suicide generates 34 YLL (53,237/1,565), and each COVID-19 death generates 8.5 YLL (90,116/10,650). Conclusions: YLL to suicide affects Sweden year after year, foremost attributable to the younger age groups, whereas YLL to COVID-19 is foremost attributable to the elderly. On average, each suicide generates four times more YLL than a COVID-19 death. Enormous efforts and resources have been put on tackling the pandemic, and without these, the burden would probably have been much larger. However, from a public health perspective, it is important to not neglect other contributors to the total burden of disease where national efforts also may have an impact. [ABSTRACT FROM AUTHOR]

Published
2022
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46. Exploring the association between use of gonadotropin releasing hormones agonists and prostate cancer diagnosis per se and diabetes control in men with type 2 diabetes mellitus: a nationwide, population-based cohort study.

Author

Lin, E., Garmo, Hans, Van Hemelrijck, Mieke, Adolfsson, Jan, Stattin, Pär, Zethelius, Björn, and Crawley, Danielle

Subjects
GONADOTROPIN releasing hormone, PROSTATE cancer, TYPE 2 diabetes, CANCER diagnosis, GLYCEMIC control, DIAGNOSIS of diabetes, DIABETES
Abstract

Background: Gonadotropin Releasing Hormones agonists (GnRH), which are first line treatment for metastatic prostate cancer (PCa), increase risk of type 2 diabetes mellitus (T2DM). This study aims to quantify the association of use of GnRH with diabetes control in PCa men with T2DM.Methods: Nationwide population-based cohort study in the Swedish National Diabetes Register and Prostate Cancer data Base Sweden 4.1, on the association between GnRH and diabetes control in T2DM men with PCa by comparing T2DM men with PCa vs. without PCa, as well as comparing T2DM men with PCa on or not on GnRH. The primary exposure was use of GnRH. Worsening diabetes control was the primary outcome, defined as: 1) HbA1c rose to 58 mmol/mol or higher; 2) HbA1c increase by 10 mmol/mol or more; 3) Start of antidiabetic drugs or switch to insulin. We also combined all above definitions. Cox proportional hazards regression was used to analyze the association.Results: There were 5714 T2DM men with PCa of whom 692 were on GnRH and 28,445 PCa-free men with T2DM with similar baseline characteristics. Diabetes control was worse in men with GnRH vs. PCa-free men (HR: 1.24, 95% CI: 1.13-1.34) as well as compared with PCa men without GnRH (HR:1.58, 95% CI: 1.39-1.80), when we defined the worsening control of diabetes by combining all definitions above.Conclusion: Use of GnRH in T2DM men with PCa was associated with worse glycemic control. The findings highlight the need to closely monitor diabetes control in men with T2DM and PCa starting GnRH. [ABSTRACT FROM AUTHOR]

Published
2021
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