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22 results on '"Elders, P. J."'

1. Update of the fracture risk prediction tool FRAX:a systematic review of potential cohorts and analysis plan

Author

Vandenput, L, Johansson, H, McCloskey, E V, Liu, E, Åkesson, K E, Anderson, F A, Azagra, R, Bager, C L, Beaudart, C, Bischoff-Ferrari, H A, Biver, E, Bruyère, O, Cauley, J A, Center, J R, Chapurlat, R, Christiansen, C, Cooper, C, Crandall, C J, Cummings, S R, da Silva, J A P, Dawson-Hughes, B, Diez-Perez, A, Dufour, A B, Eisman, J A, Elders, P J M, Ferrari, S, Fujita, Y, Fujiwara, S, Glüer, C-C, Goldshtein, I, Goltzman, D, Gudnason, V, Hall, J, Hans, D, Hoff, M, Hollick, R J, Huisman, M, Iki, M, Ish-Shalom, S, Jones, G, Karlsson, M K, Khosla, S, Kiel, D P, Koh, W-P, Koromani, F, Kotowicz, M A, Kröger, H, Kwok, T, Lamy, O, Langhammer, A, Larijani, B, Lippuner, K, Mellström, D, Merlijn, T, Nordström, A, Nordström, P, O'Neill, T W, Obermayer-Pietsch, B, Ohlsson, C, Orwoll, E S, Pasco, J A, Rivadeneira, F, Schei, B, Schott, A-M, Shiroma, E J, Siggeirsdottir, K, Simonsick, E M, Sornay-Rendu, E, Sund, R, Swart, K M A, Szulc, P, Tamaki, J, Torgerson, D J, van Schoor, N M, van Staa, T P, Vila, J, Wareham, N J, Wright, N C, Yoshimura, N, Zillikens, M C, Zwart, M, Harvey, N C, Lorentzon, M, Leslie, W D, and Kanis, J A

Subjects
SDG 3 - Good Health and Well-being, Bone Density, Hip Fractures, Risk Factors, Endocrinology, Diabetes and Metabolism, Humans, Osteoporosis, Prospective Studies, 610 Medicine & health, Risk Assessment, Osteoporotic Fractures
Abstract

We describe the collection of cohorts together with the analysis plan for an update of the fracture risk prediction tool FRAX with respect to current and novel risk factors. The resource comprises 2,138,428 participants with a follow-up of approximately 20 million person-years and 116,117 documented incident major osteoporotic fractures. INTRODUCTION The availability of the fracture risk assessment tool FRAX® has substantially enhanced the targeting of treatment to those at high risk of fracture with FRAX now incorporated into more than 100 clinical osteoporosis guidelines worldwide. The aim of this study is to determine whether the current algorithms can be further optimised with respect to current and novel risk factors. METHODS A computerised literature search was performed in PubMed from inception until May 17, 2019, to identify eligible cohorts for updating the FRAX coefficients. Additionally, we searched the abstracts of conference proceedings of the American Society for Bone and Mineral Research, European Calcified Tissue Society and World Congress of Osteoporosis. Prospective cohort studies with data on baseline clinical risk factors and incident fractures were eligible. RESULTS Of the 836 records retrieved, 53 were selected for full-text assessment after screening on title and abstract. Twelve cohorts were deemed eligible and of these, 4 novel cohorts were identified. These cohorts, together with 60 previously identified cohorts, will provide the resource for constructing an updated version of FRAX comprising 2,138,428 participants with a follow-up of approximately 20 million person-years and 116,117 documented incident major osteoporotic fractures. For each known and candidate risk factor, multivariate hazard functions for hip fracture, major osteoporotic fracture and death will be tested using extended Poisson regression. Sex- and/or ethnicity-specific differences in the weights of the risk factors will be investigated. After meta-analyses of the cohort-specific beta coefficients for each risk factor, models comprising 10-year probability of hip and major osteoporotic fracture, with or without femoral neck bone mineral density, will be computed. CONCLUSIONS These assembled cohorts and described models will provide the framework for an updated FRAX tool enabling enhanced assessment of fracture risk (PROSPERO (CRD42021227266)).

Published
2022
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3. The association between social jetlag and the metabolic syndrome and type 2 diabetes: a systematic review and meta-analysis

Author

Bouman, E. J., Beulens, J. W. J., Groeneveld, L., de Kruijk, R. S., Schoonmade, L., Remmelzwaal, S., Elders, P. J. M., Rutters, F., Epidemiology and Data Science, ACS - Diabetes & metabolism, APH - Methodology, ACS - Heart failure & arrhythmias, APH - Health Behaviors & Chronic Diseases, Obstetrics and gynaecology, General practice, and APH - Aging & Later Life

Published
2022

4. Impact of the first COVID-19 wave in the Netherlands on glycaemic control in persons with type 2 diabetes

Author

van den Berg, J. M., Holthuis, E. I. H., Baak, B. N., Overbeek, J. A., Swart, K. M. A., Blom, M. T., Elders, P. J. M., Herings, R. M. C., Radiation Oncology, Neurology, General practice, APH - Aging & Later Life, APH - Health Behaviors & Chronic Diseases, ACS - Diabetes & metabolism, Epidemiology and Data Science, APH - Quality of Care, APH - Methodology, and APH - Societal Participation & Health

Published
2022

9. The association between social jetlag, the metabolic syndrome and type 2 diabetes in a 40+year old population: the New Hoorn study

Author

Rutters, F, Koopman, A D, Rauh, S P, Van't Riet, E, Groeneveld, L, Van Der Linden, A, Beulens, J W, Elders, P J, Dekker, J M, Nijpels, G, Epidemiology and Data Science, EMGO - Lifestyle, overweight and diabetes, Gastroenterology and hepatology, General practice, and EMGO - Musculoskeletal health

Abstract

Background and aims: Social jetlag is the discrepancy between our internal circadian clock and social clock and is a measure of circadian misalignment. Previous studies have shown that up to two thirds of the general population, aged 18-35y, suffer from social jetlag and its negative effects on metabolic parameters. As data from the general population over 40+y is missing, the aim of this study is to examine the prevalence of social jetlag and the association between social jetlag, the metabolic syndrome and type 2 diabetes in a 40+yearold, population-based cohort. Materials and methods: We used cross-sectional data from the New Hoorn study cohort, n=1734, 48% male, aged 45-73y. Social jetlag was measured using a questionnaire, calculated as the difference in mid-point sleep on week and weekend days and defined as 0-1h, 1-2h or >2h social jetlag.Metabolic syndrome was defined according to the Adult Treatment Panel III, including waist circumference, hypertension and levels of fasting plasma glucose, HDL-C and triglycerides. Pre-diabetes and Type 2 diabetes were defined according to the WHO guidelines; glucose levels > 6.1 mmol/l, HbA1c > 6% or use of diabetes medication. Results: In our 40+year-old population-based cohort, we observed that only 15% of the unemployed/retired participants had social jetlag of >1h and 65% of the employed participants. In the unemployed/retired group no significant associations were observed between social jetlag status, (parameters of) metabolic syndrome and (pre-)diabetes. However, in the employed group, logistic regression adjusted for age, sex and sleep duration showed a positive association between social jetlag, metabolic syndrome and (pre-)diabetes, with respectively OR 1.1 (95%CI 0.7-1.7) and OR 1.7 (95%CI 1.2-2.4) for participants with 1-2h social jetlag, as well as OR 2.1 (95%CI 1.2-3.6) and OR 2.3 (95%CI 1.5-3.8) for >2h of social jetlag, when compared to participants with 0-1h social jetlag. Conclusion: Social jetlag is associated with metabolic syndrome and (pre-)diabetes in working, 40+year-old participants.

Published
2016
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10. Clinical medication reviews in elderly patients with polypharmacy:a cross-sectional study in Dutch community pharmacies

Author

Chau, S H, Jansen, A P D, van de Ven, P M, Hoogland, P, Elders, P J M, Hugtenburg, J G, Clinical pharmacology and pharmacy, General practice, EMGO - Quality of care, Epidemiology and Data Science, EMGO - Mental health, Anatomy and neurosciences, EMGO - Lifestyle, overweight and diabetes, and EMGO - Musculoskeletal health

Abstract

OBJECTIVE: To investigate the nature and prevalence of drug related problems (DRPs) in older patients with polypharmacy identified by community pharmacists in daily practice through means of a clinical medication review (CMR) and assess the implementation rate of proposed interventions to solve DRPs.DESIGN: A cross-sectional study METHOD: We analysed the CMR data of 3,807 older patients (≥ 65 years) with polypharmacy (≥ 5 drugs) completed in January-August 2012. Using the "Service Apotheek Medicatie Review Tool" (SAMRT, Service Pharmacy Medication Review Tool), pharmacists in 258 community pharmacies registered the patients' year of birth, gender, dispensing data, DRPs, and proposed and implemented interventions.RESULTS: Pharmacists identified a median of two DRPs (interquartile range 1-4; mean 3.0) per patient. The DRP categories overtreatment (25.5 %) and undertreatment (15.9 %) were found to occur most frequently. On average, 46.2 % of the proposed interventions to address DRPs were implemented as proposed. In 22.4 % of cases the intervention differed from the proposal, whereas in 31.3 % of cases no intervention was implemented.CONCLUSION: In daily practice, community pharmacists identified a mean of three DRPs in older patients with polypharmacy, a number comparable to that found in controlled studies. Over- or undertreatment caused nearly half of the identified DRPs. The majority (69.9%) of the proposed interventions led to an intervention for the patient.

Published
2016

11. The general practitioner in charge of treatment of patients with bipolar disorder:an exploratory study

Author

Ter Meulen, W G, Visser, H M, Elders, P J M, Kupka, R W, EMGO - Mental health, Psychiatry, Internal medicine, and General practice

Abstract

BACKGROUND: The role of the general practitioner (gp) in the treatment of severe psychiatric disorders, including bipolar disorder (bd), is under discussion.AIM: To investigate how many patients with a recognised bd are being treated for their illness exclusively in the setting of primary care and to find out how many patients are registrated as having bd on their gp's file.METHOD: We made an exploratory study in a gp's database containing data for 14,254 Dutch adult patients in the Amsterdam over a period of 3.5 years (2010-2013).RESULTS: We found that the gp was in charge of the treatment of bd in less than one patient per practice. The percentage of patients officially recognised as having bd in the database we studied was 0.15%, a percentage that is much lower than the percentage of bd in the Dutch population as a whole. There are several possible explanations for this discrepancy.CONCLUSION: Given these low numbers, it is unlikely that the gps can have adequate experience of giving their bd patients the latest type of treatment. In view of the increasing role played by gps in the treatment of bd, it is important that there is strong collaboration with specialised mental health care, and that a low threshold prevails for consultation and referral.

Published
2016

12. A Meta-Analysis of Trabecular Bone Score in Fracture Risk Prediction and Its Relationship to FRAX

Author

McCloskey, E.V., Oden, A., Harvey, N.C., Leslie, W.D., Hans, D., Johansson, H., Barkmann, R., Boutroy, S., Brown, J., Chapurlat, R., Elders, P. J. M., Fujita, Yuki, Gluer, C. C., Goltzman, D., Iki, M., Karlsson, M., Kindmark, A., Kotowicz, M., Kurumatani, N., Kwok, Terry, Lamy, O., Leung, J., Lippuner, K., Ljunggren, O., Lorentzon, M., Mellstrom, D., Merlijn, T., Oei, L., Ohlsson, C., Pasco, J. A., Rivadeneira, F., Rosengren, B., Sornay-Rendu, E., Szulc, P., Tamaki, J., Kanis, John A., Epidemiology, Internal Medicine, General practice, and EMGO - Musculoskeletal health

Subjects
Male, Lumbar Vertebrae, Hip Fractures, Models, Biological, frax, meta-analysis, trabecular bone structure, fracture, Bone Density, Risk Factors, Humans, Osteoporosis, Spinal Fractures, tbs, Female, Prospective Studies, risk
Abstract

Trabecular bone score (TBS) is a gray-level textural index of bone microarchitecture derived from lumbar spine dual-energy X-ray absorptiometry (DXA) images. TBS is a bone mineral density (BMD)-independent predictor of fracture risk. The objective of this meta-analysis was to determine whether TBS predicted fracture risk independently of FRAX probability and to examine their combined performance by adjusting the FRAX probability for TBS. We utilized individual-level data from 17,809 men and women in 14 prospective population-based cohorts. Baseline evaluation included TBS and the FRAX risk variables, and outcomes during follow-up (mean 6.7 years) comprised major osteoporotic fractures. The association between TBS, FRAX probabilities, and the risk of fracture was examined using an extension of the Poisson regression model in each cohort and for each sex and expressed as the gradient of risk (GR; hazard ratio per 1 SD change in risk variable in direction of increased risk). FRAX probabilities were adjusted for TBS using an adjustment factor derived from an independent cohort (the Manitoba Bone Density Cohort). Overall, the GR of TBS for major osteoporotic fracture was 1.44 (95% confidence interval [CI] 1.35-1.53) when adjusted for age and time since baseline and was similar in men and women (p > 0.10). When additionally adjusted for FRAX 10-year probability of major osteoporotic fracture, TBS remained a significant, independent predictor for fracture (GR = 1.32, 95% CI 1.24-1.41). The adjustment of FRAX probability for TBS resulted in a small increase in the GR (1.76, 95% CI 1.65-1.87 versus 1.70, 95% CI 1.60-1.81). A smaller change in GR for hip fracture was observed (FRAX hip fracture probability GR 2.25 vs. 2.22). TBS is a significant predictor of fracture risk independently of FRAX. The findings support the use of TBS as a potential adjustment for FRAX probability, though the impact of the adjustment remains to be determined in the context of clinical assessment guidelines. (C) 2015 American Society for Bone and Mineral Research.

Published
2015
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13. Anti-osteoporosis drug prescribing after hip fracture in the UK: 2000-2010

Author

Klop, C, Gibson-Smith, D, Elders, P J M, Welsing, P M J, Leufkens, H G M, Harvey, N C, Bijlsma, J W J, van Staa, T-P, de Vries, F, Sub Pharmacotherapy, Theoretical, Sub Pharmacoepidemiology, Pharmacoepidemiology and Clinical Pharmacology, Sub Pharmacotherapy, Theoretical, Sub Pharmacoepidemiology, Pharmacoepidemiology and Clinical Pharmacology, Psychiatry, General practice, Rheumatology, EMGO - Musculoskeletal health, Epidemiologie, and RS: CAPHRI School for Public Health and Primary Care

Subjects
Male, PRESCRIPTION, OLDER MEN, Endocrinology, Diabetes and Metabolism, medicine.medical_treatment, SUBSEQUENT FRACTURES, Osteoporosis, Kaplan-Meier Estimate, Overweight, Osteoporotic fracture, THERAPY, Endocrinology, Strontium ranelate, Recurrence, Secondary Prevention, Cumulative incidence, Practice Patterns, Physicians', VITAMIN-D, media_common, RISK, Aged, 80 and over, Hip fracture, Bone Density Conservation Agents, Middle Aged, Diabetes and Metabolism, Anti-osteoporotic drugs, POSTMENOPAUSAL WOMEN, Female, Original Article, HEALTH BELIEFS, medicine.symptom, medicine.drug, Drug, medicine.medical_specialty, media_common.quotation_subject, Drug Prescriptions, Internal medicine, MANAGEMENT, medicine, Humans, Bisphosphonate, Aged, Primary Health Care, Hip Fractures, Proportional hazards model, business.industry, CARE, medicine.disease, Drug Utilization, United Kingdom, Surgery, business, Osteoporotic Fractures
Abstract

SummaryThe probability of initiating with anti-osteoporosis therapy increased from 7 % in 2000 to 46 % in 2010. This improvement was greater for patients over the age of 75 years. Men, those overweight, having dementia or exposed to antipsychotics, sedatives/hypnotics or opioid analgesics were significantly less likely to receive anti-osteoporosis drugs.IntroductionThe objective of this study was to examine trends and determinants of anti-osteoporosis drug prescribing after hip fracture in the UK between 2000 and 2010.MethodsData were extracted from the UK Clinical Practice Research Datalink for patients ?50 years who had a first hip fracture between 2000 and 2010 and who did not currently (?6 months prior) receive anti-osteoporosis drugs (bisphosphonates, strontium ranelate, parathyroid hormone, calcitonin and raloxifene) (n?=?27,542). The cumulative incidence probability of being prescribed anti-osteoporosis drugs within 1 year after hip fracture was estimated by Kaplan-Meier life-table analyses. Determinants for treatment initiation were estimated by Cox proportional hazards models.ResultsThe probability of being prescribed any anti-osteoporosis drug after hip fracture increased from 7 % in 2000 to 46 % in 2010. This trend was more marked in patients ?75 years. The increase in prescribing of anti-osteoporosis drugs was complemented by a similar increase in vitamin D/calcium provision. Cumulative incidence of receiving anti-osteoporosis therapy was greater at any given point in time in women (8 % in 2000, 51 % in 2010) compared to men (4 % in 2000, 34 % in 2010). In addition to male gender, multivariable Cox regression identified reduced likelihood of receiving anti-osteoporosis drugs for those being overweight, having dementia and exposed to psychotropic drugs (antipsychotics, sedatives/hypnotics) or opioid analgesics.ConclusionAlthough the prescribing of anti-osteoporosis drugs after hip fracture has increased substantially since 2000, the overall rate remained inadequate, particularly in men. With the continuing increase in the absolute number of hip fractures, further research should be made into the barriers to optimise osteoporosis management.

Published
2015
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14. The risk of major and any (non-hip) fragility fracture after hip fracture in the United Kingdom: 2000-2010

Author

Gibson-Smith, D, Klop, C, Elders, P J M, Welsing, P M J, van Schoor, N, Leufkens, H G M, Harvey, N C, van Staa, T P, de Vries, F, Pharmacoepidemiology and Clinical Pharmacology, Sub Pharmacoepidemiology, Sub Pharmacotherapy, Theoretical, Pharmacoepidemiology and Clinical Pharmacology, Sub Pharmacoepidemiology, Sub Pharmacotherapy, Theoretical, Psychiatry, General practice, Epidemiology and Data Science, EMGO - Musculoskeletal health, Epidemiologie, RS: CAPHRI School for Public Health and Primary Care, MUMC+: DA CDL Algemeen (9), and RS: CAPHRI - Clinical epidemiology

Subjects
Male, medicine.medical_specialty, Secular trends, SUBSEQUENT FRACTURE, DATABASE, Endocrinology, Diabetes and Metabolism, Osteoporosis, Population, Comorbidity, Osteoporotic fracture, OSTEOPOROSIS, Risk Assessment, Age Distribution, Recurrence, Risk Factors, Internal medicine, BISPHOSPHONATES, medicine, Humans, Cumulative incidence, Sex Distribution, education, POPULATION, Aged, Aged, 80 and over, Hip fracture, education.field_of_study, business.industry, Hip Fractures, Incidence (epidemiology), Incidence, MORTALITY, Hazard ratio, WOMEN, FALLS, Middle Aged, medicine.disease, TRENDS, United Kingdom, Orthopedic surgery, Fracture (geology), SURVIVAL, Female, business, Osteoporotic Fractures
Abstract

UNLABELLED: The risk of a subsequent major or any fracture after a hip fracture and secular trends herein were examined. Within 1 year, 2.7 and 8.4% of patients sustained a major or any (non-hip) fracture, which increased to 14.7 and 32.5% after 5 years. Subsequent fracture rates increased during the study period both for major and any (non-hip) fracture. INTRODUCTION: Hip fractures are associated with subsequent fractures, particularly in the year following initial fracture. Age-adjusted hip fracture rates have stabilised in many developed countries, but secular trends in subsequent fracture remain poorly documented. We thus evaluated secular trends (2000-2010) and determinants for the risk of a subsequent major (humerus, vertebral, or forearm) and any (non-hip) fracture after hip fracture. METHODS: Patients ≥50 years with a hip fracture between 2000 and 2010 were extracted from the UK Clinical Practice Research Datalink (n = 30,516). Incidence rates, cumulative incidence probabilities, and adjusted hazard ratios (aHRs) were calculated. RESULTS: Within 1 year following hip fracture, 2.7 and 8.4% of patients sustained a major or any (non-hip) fracture, which increased to 14.7 and 32.5% after 5 years, respectively. The most important risk factors for a subsequent major fracture within 1 year were the female gender [aHR 1.90, 95% confidence interval (CI) 1.51-2.40] and a history of secondary osteoporosis (aHR 1.54, 95% CI 1.17-2.02). The annual risk increased during the study period for both subsequent major (2009-2010 vs. 2000-2002: aHR 1.44, 95% CI 1.12-1.83) and any (non-hip) facture (2009-2010 vs. 2000-2002: aHR 1.80, 95% CI 1.58-2.06). CONCLUSION: The risk of sustaining a major or any (non-hip) fracture after hip fracture is small in the first year. However, given the recent rise in secondary fracture rates and the substantial risk of subsequent fracture in the longer term, fracture prevention is clearly indicated for patients who have sustained a hip fracture.

Published
2014
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18. Bewegen en vallen

Author

Schooten, K. S., Pijnappels, M. A. G. M., Rispens, S. M., Elders, P. J. M., Lips, P. T. A. M., Andreas Daffertshofer, Peter Beek, and Jaap van Dieen

22. The power of genetic diversity in genome-wide association studies of lipids

Author

Graham, Sarah E, Clarke, Shoa L, Wu, Kuan-Han H, Kanoni, Stavroula, Zajac, Greg JM, Ramdas, Shweta, Surakka, Ida, Ntalla, Ioanna, Vedantam, Sailaja, Winkler, Thomas W, Locke, Adam E, Marouli, Eirini, Hwang, Mi Yeong, Han, Sohee, Narita, Akira, Choudhury, Ananyo, Bentley, Amy R, Ekoru, Kenneth, Verma, Anurag, Trivedi, Bhavi, Martin, Hilary C, Hunt, Karen A, Hui, Qin, Klarin, Derek, Zhu, Xiang, Thorleifsson, Gudmar, Helgadottir, Anna, Gudbjartsson, Daniel F, Holm, Hilma, Olafsson, Isleifur, Akiyama, Masato, Sakaue, Saori, Terao, Chikashi, Kanai, Masahiro, Zhou, Wei, Brumpton, Ben M, Rasheed, Humaira, Ruotsalainen, Sanni E, Havulinna, Aki S, Veturi, Yogasudha, Feng, QiPing, Rosenthal, Elisabeth A, Lingren, Todd, Pacheco, Jennifer Allen, Pendergrass, Sarah A, Haessler, Jeffrey, Giulianini, Franco, Bradford, Yuki, Miller, Jason E, Campbell, Archie, Lin, Kuang, Millwood, Iona Y, Hindy, George, Rasheed, Asif, Faul, Jessica D, Zhao, Wei, Weir, David R, Turman, Constance, Huang, Hongyan, Graff, Mariaelisa, Mahajan, Anubha, Brown, Michael R, Zhang, Weihua, Yu, Ketian, Schmidt, Ellen M, Pandit, Anita, Gustafsson, Stefan, Yin, Xianyong, Luan, Jian’an, Zhao, Jing-Hua, Matsuda, Fumihiko, Jang, Hye-Mi, Yoon, Kyungheon, Medina-Gomez, Carolina, Pitsillides, Achilleas, Hottenga, Jouke Jan, Willemsen, Gonneke, Wood, Andrew R, Ji, Yingji, Gao, Zishan, Haworth, Simon, Mitchell, Ruth E, Chai, Jin Fang, Aadahl, Mette, Yao, Jie, Manichaikul, Ani, Warren, Helen R, Ramirez, Julia, Bork-Jensen, Jette, Kårhus, Line L, Goel, Anuj, Sabater-Lleal, Maria, Noordam, Raymond, Sidore, Carlo, Fiorillo, Edoardo, McDaid, Aaron F, Marques-Vidal, Pedro, Wielscher, Matthias, Trompet, Stella, Sattar, Naveed, Møllehave, Line T, Thuesen, Betina H, Munz, Matthias, Zeng, Lingyao, Huang, Jianfeng, Yang, Bin, Poveda, Alaitz, Kurbasic, Azra, Lamina, Claudia, Forer, Lukas, Scholz, Markus, Galesloot, Tessel E., Bradfield, Jonathan P., Daw, E Warwick, Zmuda, Joseph M, Mitchell, Jonathan S, Fuchsberger, Christian, Christensen, Henry, Brody, Jennifer A, Feitosa, Mary F, Wojczynski, Mary K, Preuss, Michael, Mangino, Massimo, Christofidou, Paraskevi, Verweij, Niek, Benjamins, Jan W, Engmann, Jorgen, Kember, Rachel L, Slieker, Roderick C, Lo, Ken Sin, Zilhao, Nuno R, Le, Phuong, Kleber, Marcus E, Delgado, Graciela E, Huo, Shaofeng, Ikeda, Daisuke D, Iha, Hiroyuki, Yang, Jian, Liu, Jun, Leonard, Hampton L, Marten, Jonathan, Schmidt, Börge, Arendt, Marina, Smyth, Laura J, Cañadas-Garre, Marisa, Wang, Chaolong, Nakatochi, Masahiro, Wong, Andrew, Hutri-Kähönen, Nina, Sim, Xueling, Xia, Rui, Huerta-Chagoya, Alicia, Fernandez-Lopez, Juan Carlos, Lyssenko, Valeriya, Ahmed, Meraj, Jackson, Anne U, Irvin, Marguerite R, Oldmeadow, Christopher, Kim, Han-Na, Ryu, Seungho, Timmers, Paul RHJ, Arbeeva, Liubov, Dorajoo, Rajkumar, Lange, Leslie A, Chai, Xiaoran, Prasad, Gauri, Lorés-Motta, Laura, Pauper, Marc, Long, Jirong, Li, Xiaohui, Theusch, Elizabeth, Takeuchi, Fumihiko, Spracklen, Cassandra N, Loukola, Anu, Bollepalli, Sailalitha, Warner, Sophie C, Wang, Ya Xing, Wei, Wen B., Nutile, Teresa, Ruggiero, Daniela, Sung, Yun Ju, Hung, Yi-Jen, Chen, Shufeng, Liu, Fangchao, Yang, Jingyun, Kentistou, Katherine A, Gorski, Mathias, Brumat, Marco, Meidtner, Karina, Bielak, Lawrence F, Smith, Jennifer A, Hebbar, Prashantha, Farmaki, Aliki-Eleni, Hofer, Edith, Lin, Maoxuan, Xue, Chao, Zhang, Jifeng, Concas, Maria Pina, Vaccargiu, Simona, van der Most, Peter J, Pitkänen, Niina, Cade, Brian E, Lee, Jiwon, van der Laan, Sander W., Chitrala, Kumaraswamy Naidu, Weiss, Stefan, Zimmermann, Martina E, Lee, Jong Young, Choi, Hyeok Sun, Nethander, Maria, Freitag-Wolf, Sandra, Southam, Lorraine, Rayner, Nigel W, Wang, Carol A, Lin, Shih-Yi, Wang, Jun-Sing, Couture, Christian, Lyytikäinen, Leo-Pekka, Nikus, Kjell, Cuellar-Partida, Gabriel, Vestergaard, Henrik, Hildalgo, Bertha, Giannakopoulou, Olga, Cai, Qiuyin, Obura, Morgan O, van Setten, Jessica, Li, Xiaoyin, Schwander, Karen, Terzikhan, Natalie, Shin, Jae Hun, Jackson, Rebecca D, Reiner, Alexander P, Martin, Lisa Warsinger, Chen, Zhengming, Li, Liming, Highland, Heather M, Young, Kristin L, Kawaguchi, Takahisa, Thiery, Joachim, Bis, Joshua C, Nadkarni, Girish N., Launer, Lenore J, Li, Huaixing, Nalls, Mike A, Raitakari, Olli T, Ichihara, Sahoko, Wild, Sarah H, Nelson, Christopher P, Campbell, Harry, Jäger, Susanne, Nabika, Toru, Al-Mulla, Fahd, Niinikoski, Harri, Braund, Peter S, Kolcic, Ivana, Kovacs, Peter, Giardoglou, Tota, Katsuya, Tomohiro, Bhatti, Konain Fatima, de Kleijn, Dominique, de Borst, Gert J., Kim, Eung Kweon, Adams, Hieab H.H., Ikram, M. Arfan, Zhu, Xiaofeng, Asselbergs, Folkert W, Kraaijeveld, Adriaan O, Beulens, Joline WJ, Shu, Xiao-Ou, Rallidis, Loukianos S, Pedersen, Oluf, Hansen, Torben, Mitchell, Paul, Hewitt, Alex W, Kähönen, Mika, Pérusse, Louis, Bouchard, Claude, Tönjes, Anke, Chen, Yii-Der Ida, Pennell, Craig E, Mori, Trevor A, Lieb, Wolfgang, Franke, Andre, Ohlsson, Claes, Mellström, Dan, Cho, Yoon Shin, Lee, Hyejin, Yuan, Jian-Min, Koh, Woon-Puay, Rhee, Sang Youl, Woo, Jeong-Taek, Heid, Iris M, Stark, Klaus J, Völzke, Henry, Homuth, Georg, Evans, Michele K, Zonderman, Alan B, Polasek, Ozren, Pasterkamp, Gerard, Hoefer, Imo E, Redline, Susan, Pahkala, Katja, Oldehinkel, Albertine J, Snieder, Harold, Biino, Ginevra, Schmidt, Reinhold, Schmidt, Helena, Chen, Y Eugene, Bandinelli, Stefania, Dedoussis, George, Thanaraj, Thangavel Alphonse, Kardia, Sharon LR, Kato, Norihiro, Schulze, Matthias B, Girotto, Giorgia, Jung, Bettina, Böger, Carsten A, Joshi, Peter K, Bennett, David A, De Jager, Philip L, Lu, Xiangfeng, Mamakou, Vasiliki, Brown, Morris, Caulfield, Mark J, Munroe, Patricia B, Guo, Xiuqing, Ciullo, Marina, Jonas, Jost B., Samani, Nilesh J, Chasman, Daniel I., Kaprio, Jaakko, Pajukanta, Päivi, Tusié-Luna, Teresa, Aguilar-Salinas, Carlos A, Adair, Linda S, Bechayda, Sonny Augustin, de Silva, H. 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M., Ramdas, S., Surakka, I., Ntalla, I., Vedantam, S., Winkler, T. W., Locke, A. E., Marouli, E., Hwang, M. Y., Han, S., Narita, A., Choudhury, A., Bentley, A. R., Ekoru, K., Verma, A., Trivedi, B., Martin, H. C., Hunt, K. A., Hui, Q., Klarin, D., Zhu, X., Thorleifsson, G., Helgadottir, A., Gudbjartsson, D. F., Holm, H., Olafsson, I., Akiyama, M., Sakaue, S., Terao, C., Kanai, M., Zhou, W., Brumpton, B. M., Rasheed, H., Ruotsalainen, S. E., Havulinna, A. S., Veturi, Y., Feng, Q. P., Rosenthal, E. A., Lingren, T., Pacheco, J. A., Pendergrass, S. A., Haessler, J., Giulianini, F., Bradford, Y., Miller, J. E., Campbell, A., Lin, K., Millwood, I. Y., Hindy, G., Rasheed, A., Faul, J. D., Zhao, W., Weir, D. R., Turman, C., Huang, H., Graff, M., Mahajan, A., Brown, M. R., Zhang, W., Yu, K., Schmidt, E. M., Pandit, A., Gustafsson, S., Yin, X., Luan, J., Zhao, J. -H., Matsuda, F., Jang, H. -M., Yoon, K., Medina-Gomez, C., Pitsillides, A., Hottenga, J. J., Willemsen, G., Wood, A. 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J., Canadas-Garre, M., Wang, C., Nakatochi, M., Wong, A., Hutri-Kahonen, N., Sim, X., Xia, R., Huerta-Chagoya, A., Fernandez-Lopez, J. C., Lyssenko, V., Ahmed, M., Jackson, A. U., Irvin, M. R., Oldmeadow, C., Kim, H. -N., Ryu, S., Timmers, P. R. H. J., Arbeeva, L., Dorajoo, R., Lange, L. A., Chai, X., Prasad, G., Lores-Motta, L., Pauper, M., Long, J., Li, X., Theusch, E., Takeuchi, F., Spracklen, C. N., Loukola, A., Bollepalli, S., Warner, S. C., Wang, Y. X., Wei, W. B., Nutile, T., Ruggiero, D., Sung, Y. J., Hung, Y. -J., Chen, S., Liu, F., Kentistou, K. A., Gorski, M., Brumat, M., Meidtner, K., Bielak, L. F., Smith, J. A., Hebbar, P., Farmaki, A. -E., Hofer, E., Lin, M., Xue, C., Zhang, J., Concas, M. P., Vaccargiu, S., van der Most, P. J., Pitkanen, N., Cade, B. E., Lee, J., van der Laan, S. W., Chitrala, K. N., Weiss, S., Zimmermann, M. E., Lee, J. Y., Choi, H. S., Nethander, M., Freitag-Wolf, S., Southam, L., Rayner, N. W., Wang, C. 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A., Lieb, W., Franke, A., Ohlsson, C., Mellstrom, D., Cho, Y. S., Lee, H., Yuan, J. -M., Koh, W. -P., Rhee, S. Y., Woo, J. -T., Heid, I. M., Stark, K. J., Volzke, H., Homuth, G., Evans, M. K., Zonderman, A. B., Polasek, O., Pasterkamp, G., Hoefer, I. E., Redline, S., Pahkala, K., Oldehinkel, A. J., Snieder, H., Biino, G., Schmidt, R., Schmidt, H., Chen, Y. E., Bandinelli, S., Dedoussis, G., Thanaraj, T. A., Kardia, S. L. R., Kato, N., Schulze, M. B., Girotto, G., Jung, B., Boger, C. A., Joshi, P. K., Bennett, D. A., De Jager, P. L., Lu, X., Mamakou, V., Brown, M., Caulfield, M. J., Munroe, P. B., Guo, X., Ciullo, M., Jonas, J. B., Samani, N. J., Kaprio, J., Pajukanta, P., Adair, L. S., Bechayda, S. A., de Silva, H. J., Wickremasinghe, A. R., Krauss, R. M., Wu, J. -Y., Zheng, W., den Hollander, A. I., Bharadwaj, D., Correa, A., Wilson, J. G., Lind, L., Heng, C. -K., Nelson, A. E., Golightly, Y. M., Wilson, J. F., Penninx, B., Kim, H. -L., Attia, J., Scott, R. J., Rao, D. C., Arnett, D. K., Walker, M., Koistinen, H. A., Chandak, G. R., Yajnik, C. S., Mercader, J. M., Tusie-Luna, T., Aguilar-Salinas, C. A., Villalpando, C. G., Orozco, L., Fornage, M., Tai, E. S., van Dam, R. M., Lehtimaki, T., Chaturvedi, N., Yokota, M., Reilly, D. F., Mcknight, A. J., Kee, F., Jockel, K. -H., Mccarthy, M. I., Palmer, C. N. A., Vitart, V., Hayward, C., Simonsick, E., van Duijn, C. M., Lu, F., Qu, J., Hishigaki, H., Lin, X., Marz, W., Parra, E. J., Cruz, M., Gudnason, V., Tardif, J. -C., Lettre, G., 't Hart, L. M., Elders, P. J. M., Damrauer, S. M., Kumari, M., Kivimaki, M., van der Harst, P., Spector, T. D., Loos, R. J. F., Province, M. A., Psaty, B. M., Brandslund, I., Pramstaller, P. P., Christensen, K., Ripatti, S., Widen, E., Hakonarson, H., Grant, S. F. A., Kiemeney, L. A. L. M., de Graaf, J., Loeffler, M., Kronenberg, F., Gu, D., Erdmann, J., Schunkert, H., Franks, P. W., Linneberg, A., Jukema, J. W., Khera, A. 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D., Jousilahti, P., Salomaa, V., Hveem, K., Asvold, B. O., Kubo, M., Kamatani, Y., Okada, Y., Murakami, Y., Thorsteinsdottir, U., Stefansson, K., Ho, Y. -L., Lynch, J. A., Rader, D. J., Tsao, P. S., Chang, K. -M., Cho, K., O'Donnell, C. J., Gaziano, J. M., Wilson, P., Rotimi, C. N., Hazelhurst, S., Ramsay, M., Trembath, R. C., van Heel, D. A., Tamiya, G., Yamamoto, M., Kim, B. -J., Mohlke, K. L., Frayling, T. M., Hirschhorn, J. N., Kathiresan, S., Boehnke, M., Natarajan, P., Peloso, G. M., Brown, C. D., Morris, A. P., Assimes, T. L., Deloukas, P., Sun, Y. V., Willer, C. J., Interdisciplinary Centre Psychopathology and Emotion regulation (ICPE), Life Course Epidemiology (LCE), Cardiovascular Centre (CVC), Biological Psychology, APH - Health Behaviors & Chronic Diseases, APH - Personalized Medicine, APH - Mental Health, APH - Methodology, AMS - Ageing & Vitality, and AMS - Sports

Subjects
blood lipid level, Multifactorial Inheritance, GWAS, blood lipid levels, cardiovascular disease, Vascular damage Radboud Institute for Health Sciences [Radboudumc 16], Medizin, LOCI, ANCESTRY, VARIANTS, Polymorphism, Single Nucleotide, Linkage Disequilibrium, Sensory disorders Donders Center for Medical Neuroscience [Radboudumc 12], Article, Population Groups, SDG 3 - Good Health and Well-being, Humans, Genetic Predisposition to Disease, METAANALYSIS, POLYMORPHISMS, RISK, Multidisciplinary, Cardiovascular Diseases, Genome-Wide Association Study, Cardiovascular Diseases/genetics, Genetic Predisposition to Disease/genetics, Genome-Wide Association Study/methods, Polymorphism, Single Nucleotide/genetics, CHOLESTEROL, Human Genetics, INDIVIDUALS, Urological cancers Radboud Institute for Health Sciences [Radboudumc 15], DISCOVERY, LOW-FREQUENCY, Delivery of Health Care
Abstract

Increased blood lipid levels are heritable risk factors of cardiovascular disease with varied prevalence worldwide owing to different dietary patterns and medication use 1 . Despite advances in prevention and treatment, in particular through reducing low-density lipoprotein cholesterol levels 2 , heart disease remains the leading cause of death worldwide 3 . Genome-wideassociation studies (GWAS) of blood lipid levels have led to important biological and clinical insights, as well as new drug targets, for cardiovascular disease. However, most previous GWAS 4-23 have been conducted in European ancestry populations and may have missed genetic variants that contribute to lipid-level variation in other ancestry groups. These include differences in allele frequencies, effect sizes and linkage-disequilibrium patterns 24 . Here we conduct a multi-ancestry, genome-wide genetic discovery meta-analysis of lipid levels in approximately 1.65 million individuals, including 350,000 of non-European ancestries. We quantify the gain in studying non-European ancestries and provide evidence to support the expansion of recruitment of additional ancestries, even with relatively small sample sizes. We find that increasing diversity rather than studying additional individuals of European ancestry results in substantial improvements in fine-mapping functional variants and portability of polygenic prediction (evaluated in approximately 295,000 individuals from 7 ancestry groupings). Modest gains in the number of discovered loci and ancestry-specific variants were also achieved. As GWAS expand emphasis beyond the identification of genes and fundamental biology towards the use of genetic variants for preventive and precision medicine 25 , we anticipate that increased diversity of participants will lead to more accurate and equitable 26 application of polygenic scores in clinical practice.

Published
2021
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