[en] Cardiometabolic health is complex and characterized by an ensemble of correlated and/or co-occurring conditions including obesity, dyslipidemia, hypertension, and diabetes mellitus. It is affected by social, lifestyle, and environmental factors, which in-turn exhibit complex correlation patterns. To account for the complexity of (i) exposure profiles and (ii) health outcomes, we propose to use a multitrait Bayesian variable selection approach and identify a sparse set of exposures jointly explanatory of the complex cardiometabolic health status. Using data from a subset (N = 941 participants) of the nutrition, environment, and cardiovascular health (NESCAV) study, we evaluated the link between measurements of the cumulative exposure to (N = 33) pollutants derived from hair and cardiometabolic health as proxied by up to nine measured traits. Our multitrait analysis showed increased statistical power, compared to single-trait analyses, to detect subtle contributions of exposures to a set of clinical phenotypes, while providing parsimonious results with improved interpretability. We identified six exposures that were jointly explanatory of cardiometabolic health as modeled by six complementary traits, of which, we identified strong associations between hexachlorobenzene and trifluralin exposure and adverse cardiometabolic health, including traits of obesity, dyslipidemia, and hypertension. This supports the use of this type of approach for the joint modeling, in an exposome context, of correlated exposures in relation to complex and multifaceted outcomes.
Disciplines :
Public health, health care sciences & services
Author, co-author :
Wada, Rin ; Department of Epidemiology and Biostatistics, School of Public Health Imperial College London, London W2 1PG, U.K ; MRC Centre for Environment and Health Imperial College London, London W2 1PG, U.K
Peng, Feng-Jiao ; Human Biomonitoring Research Unit, Department of Precision Health, Luxembourg Institute of Health, Strassen L-1445, Luxembourg
Lin, Chia-An; Department of Epidemiology and Biostatistics, School of Public Health Imperial College London, London W2 1PG, U.K
Vermeulen, Roel ; Department of Epidemiology and Biostatistics, School of Public Health Imperial College London, London W2 1PG, U.K ; Institute for Risk Assessment Sciences, Utrecht University, Utrecht 3584 CM, The Netherlands
Iglesias-González, Alba; Human Biomonitoring Research Unit, Department of Precision Health, Luxembourg Institute of Health, Strassen L-1445, Luxembourg
Palazzi, Paul; Human Biomonitoring Research Unit, Department of Precision Health, Luxembourg Institute of Health, Strassen L-1445, Luxembourg
Bodinier, Barbara; Department of Epidemiology and Biostatistics, School of Public Health Imperial College London, London W2 1PG, U.K ; MRC Centre for Environment and Health Imperial College London, London W2 1PG, U.K
Streel, Sylvie ; Université de Liège - ULiège > Département des sciences de la santé publique
Guillaume, Michèle ; Université de Liège - ULiège > Département des sciences de la santé publique > Santé publique : aspects spécifiques
Vuckovic, Dragana; Department of Epidemiology and Biostatistics, School of Public Health Imperial College London, London W2 1PG, U.K ; MRC Centre for Environment and Health Imperial College London, London W2 1PG, U.K
Dagnino, Sonia; Department of Epidemiology and Biostatistics, School of Public Health Imperial College London, London W2 1PG, U.K ; Transporters in Imaging and Radiotherapy in Oncology (TIRO), Institut des sciences du vivant Fréderic Joliot, CEA, Université Côte d'Azur, Nice 06107, France
Chiquet, Julien; Université Paris-Saclay, AgroParisTech, INRAE, UMR MIA Paris-Saclay, Palaiseau 91120, France
Appenzeller, Brice M R ; Human Biomonitoring Research Unit, Department of Precision Health, Luxembourg Institute of Health, Strassen L-1445, Luxembourg
Chadeau-Hyam, Marc ; Department of Epidemiology and Biostatistics, School of Public Health Imperial College London, London W2 1PG, U.K ; MRC Centre for Environment and Health Imperial College London, London W2 1PG, U.K
The NESCAV study was supported by INTERREG IV A program “Greater Region”, 2007–2013. This work has been supported by the ‘Healthy choices across social gradients’ project (Research Council of Norway, project #289440). R.W., R.V., B.B., S.D., D.V., and MC-H also acknowledge the support from the H2020-EXPANSE (grant #874627) and LongITools (grant #874739) projects.
Wild, C. P. Complementing the Genome with an “Exposome”: The Outstanding Challenge of Environmental Exposure Measurement in Molecular Epidemiology. Cancer Epidemiol. Biomarkers Prev. 2005, 14, 1847- 1850, 10.1158/1055-9965.EPI-05-0456
Wild, C. P. The exposome: from concept to utility. Int. J. Epidemiol. 2012, 41, 24- 32, 10.1093/ije/dyr236
Vermeulen, R.; Schymanski, E. L.; Barabási, A. L.; Miller, G. W. The exposome and health: Where chemistry meets biology. Science 2020, 367, 392- 396, 10.1126/science.aay3164
Appenzeller, B. M.; Tsatsakis, A. M. Hair analysis for biomonitoring of environmental and occupational exposure to organic pollutants: State of the art, critical review and future needs. Toxicol. Lett. 2012, 210, 119- 140, 10.1016/j.toxlet.2011.10.021 Advances on biomonitoring and exposure assessment for pesticides and persistent organic pollutants
Appenzeller, B. M. R.; Hardy, E. M.; Grova, N.; Chata, C.; Faÿs, F.; Briand, O.; Schroeder, H.; Duca, R.-C. Hair analysis for the biomonitoring of pesticide exposure: comparison with blood and urine in a rat model. Arch. Toxicol. 2017, 91, 2813- 2825, 10.1007/s00204-016-1910-9
Hardy, E. M.; Duca, R. C.; Salquebre, G.; Appenzeller, B. M. Multi-residue analysis of organic pollutants in hair and urine for matrices comparison. Forensic Sci. Int. 2015, 249, 6- 19, 10.1016/j.forsciint.2014.12.003
Tsatsakis, A.; Tzatzarakis, M.; Tutudaki, M.; Babatsikou, F.; Alegakis, A.; Koutis, C. Assessment of levels of organochlorine pesticides and their metabolites in the hair of a Greek rural human population. Hum. Exp. Toxicol. 2008, 27, 933- 940, 10.1177/0960327108102047 PMID: 19273549
Peng, F.-J.; Hardy, E. M.; Béranger, R.; Mezzache, S.; Bourokba, N.; Bastien, P.; Li, J.; Zaros, C.; Chevrier, C.; Palazzi, P.; Soeur, J.; Appenzeller, B. M. Human exposure to PCBs, PBDEs and bisphenols revealed by hair analysis: A comparison between two adult female populations in China and France. Environ. Pollut. 2020, 267, 115425, 10.1016/j.envpol.2020.115425
Peng, F.-J.; Palazzi, P.; Viguié, C.; Appenzeller, B. M. Measurement of hair thyroid and steroid hormone concentrations in the rat evidence endocrine disrupting potential of a low dose mixture of polycyclic aromatic hydrocarbons. Environ. Pollut. 2022, 313, 120179, 10.1016/j.envpol.2022.120179
Ren, M.; Yan, L.; Pang, Y.; Jia, X.; Huang, J.; Shen, G.; Cheng, H.; Wang, X.; Pan, B.; Li, Z.; Wang, B. External interference from ambient air pollution on using hair metal(loid)s for biomarker-based exposure assessment. Environ. Int. 2020, 137, 105584, 10.1016/j.envint.2020.105584
Ren, M.; Jia, X.; Shi, J.; Yan, L.; Li, Z.; Lan, C.; Chen, J.; Li, N.; Li, K.; Huang, J.; Wu, S.; Lu, Q.; Li, Z.; Wang, B.; Liu, J. Simultaneous analysis of typical halogenated endocrine disrupting chemicals and metal(loid)s in human hair. Sci. Total Environ. 2020, 718, 137300, 10.1016/j.scitotenv.2020.137300
Ren, M.; Fang, M.; Liu, J.; Lu, Q.; Bao, H.; Zhuang, L.; Meng, F.; Pan, B.; Yan, L.; Li, Z. Applying hair exposome for linking environmental exposure to reproductive health: A comprehensive review and research perspective. Hyg. Environ. Health Adv. 2024, 9, 100086, 10.1016/j.heha.2023.100086
Visseren, F. L. J.; Mach, F.; Smulders, Y. M.; Carballo, D.; Koskinas, K. C.; Bäck, M.; Benetos, A.; Biffi, A.; Boavida, J. M.; Capodanno, D. 2021 ESC Guidelines on cardiovascular disease prevention in clinical practice: Developed by the Task Force for cardiovascular disease prevention in clinical practice with representatives of the European Society of Cardiology and 12 medical societies With the special contribution of the European Association of Preventive Cardiology (EAPC). Eur. Heart J. 2021, 42, 3227- 3337, 10.1093/eurheartj/ehab484
Cosselman, K. E.; Navas-Acien, A.; Kaufman, J. D. Environmental factors in cardiovascular disease. Nat. Rev. Cardiol. 2015, 12, 627- 642, 10.1038/nrcardio.2015.152
Bhatnagar, A. Cardiovascular pathophysiology of environmental pollutants. Am. J. Physiol.-Heart Circ. Physiol. 2004, 286, H479- H485, 10.1152/ajpheart.00817.2003 PMID: 14715496
Al-Kindi, S. G.; Brook, R. D.; Biswal, S.; Rajagopalan, S. Environmental determinants of cardiovascular disease: lessons learned from air pollution. Nat. Rev. Cardiol. 2020, 17, 656- 672, 10.1038/s41569-020-0371-2
Solenkova, N. V.; Newman, J. D.; Berger, J. S.; Thurston, G.; Hochman, J. S.; Lamas, G. A. Metal pollutants and cardiovascular disease: Mechanisms and consequences of exposure. Am. Heart J. 2014, 168, 812- 822, 10.1016/j.ahj.2014.07.007
Lind, L.; Lind, P. M. Can persistent organic pollutants and plastic-associated chemicals cause cardiovascular disease?. J. Intern. Med. 2012, 271, 537- 553, 10.1111/j.1365-2796.2012.02536.x
Perkins, J. T.; Petriello, M. C.; Newsome, B. J.; Hennig, B. Polychlorinated biphenyls and links to cardiovascular disease. Environ. Sci. Pollut. Res. 2016, 23, 2160- 2172, 10.1007/s11356-015-4479-6
Evangelou, E.; Ntritsos, G.; Chondrogiorgi, M.; Kavvoura, F. K.; Hernández, A. F.; Ntzani, E. E.; Tzoulaki, I. Exposure to pesticides and diabetes: A systematic review and meta-analysis. Environ. Int. 2016, 91, 60- 68, 10.1016/j.envint.2016.02.013
Czajka, M.; Matysiak-Kucharek, M.; Jodłowska-Jędrych, B.; Sawicki, K.; Fal, B.; Drop, B.; Kruszewski, M.; Kapka-Skrzypczak, L. Organophosphorus pesticides can influence the development of obesity and type 2 diabetes with concomitant metabolic changes. Environ. Res. 2019, 178, 108685, 10.1016/j.envres.2019.108685
Hernández-Mariano, J. Á.; Baltazar-Reyes, M. C.; Salazar-Martínez, E.; Cupul-Uicab, L. A. Exposure to the pesticide DDT and risk of diabetes and hypertension: Systematic review and meta-analysis of prospective studies. Int. J. Hyg. Environ. Health 2022, 239, 113865, 10.1016/j.ijheh.2021.113865
Alkerwi, A.; Guillaume, M.; Zannad, F.; Laufs, U.; Lair, M.-L. Nutrition, environment and cardiovascular health (NESCAV): protocol of an inter-regional cross-sectional study. BMC Public Health 2010, 10, 698, 10.1186/1471-2458-10-698
Grundy, S. M.; Brewer, H. B.; Cleeman, J. I.; Smith, S. C.; Lenfant, C.; Franklin, B. A.; Gordon, D. J.; Krauss, R. M.; Savage, P. J.; Smith Jr, S. C. Definition of metabolic syndrome: Report of the National Heart, Lung, and Blood Institute/American Heart Association conference on scientific issues related to definition. Circulation 2004, 109, 433- 438, 10.1161/01.cir.0000111245.75752.c6
Grundy, S. M.; Cleeman, J. I.; Daniels, S. R.; Donato, K. A.; Eckel, R. H.; Franklin, B. A.; Gordon, D. J.; Krauss, R. M.; Savage, P. J.; Smith, S. C.; Spertus, J. A.; Costa, F. Diagnosis and Management of the Metabolic Syndrome. Circulation 2005, 112, 2735- 2752, 10.1161/CIRCULATIONAHA.105.169404
Alkerwi, A.; Sauvageot, N.; Donneau, A.-F.; Lair, M.-L.; Couffignal, S.; Beissel, J.; Delagardelle, C.; Wagener, Y.; Albert, A.; Guillaume, M. First nationwide survey on cardiovascular risk factors in Grand-Duchy of Luxembourg (ORISCAV-LUX). BMC Public Health 2010, 10, 468, 10.1186/1471-2458-10-468
Alkerwi, A.; Vernier, C.; Sauvageot, N.; Crichton, G. E.; Elias, M. F. Demographic and socioeconomic disparity in nutrition: application of a novel Correlated Component Regression approach. BMJ Open 2015, 5, e006814 10.1136/bmjopen-2014-006814
Sauvageot, N.; Alkerwi, A.; Albert, A.; Guillaume, M. Use of food frequency questionnaire to assess relationships between dietary habits and cardiovascular risk factors in NESCAV study: validation with biomarkers. Nutr. J. 2013, 12, 143, 10.1186/1475-2891-12-143
Streel, S.; Donneau, A. F.; Hoge, A.; Majerus, S.; Kolh, P.; Chapelle, J. P.; Albert, A.; Guillaume, M.; Guillaume, M. Socioeconomic Impact on the Prevalence of Cardiovascular Risk Factors in Wallonia, Belgium: A Population-Based Study. BioMed Res. Int. 2015, 2015, 1- 10, 10.1155/2015/580849
Peng, F.-J.; Emond, C.; Hardy, E. M.; Sauvageot, N.; Alkerwi, A.; Lair, M.-L.; Appenzeller, B. M. Population-based biomonitoring of exposure to persistent and non-persistent organic pollutants in the Grand Duchy of Luxembourg: Results from hair analysis. Environ. Int. 2021, 153, 106526, 10.1016/j.envint.2021.106526
Peng, F.-J.; Lin, C.-A.; Wada, R.; Bodinier, B.; Iglesias-González, A.; Palazzi, P.; Streel, S.; Guillaume, M.; Vuckovic, D.; Chadeau-Hyam, M.; Appenzeller, B. M. Association of hair polychlorinated biphenyls and multiclass pesticides with obesity, diabetes, hypertension and dyslipidemia in NESCAV study. J. Hazard. Mater. 2024, 461, 132637, 10.1016/j.jhazmat.2023.132637
Kintz, P.; Salomone, A.; Vincenti, M. Hair Analysis in Clinical and Forensic Toxicology; Academic Press, 2015.
Hardy, E. M.; Dereumeaux, C.; Guldner, L.; Briand, O.; Vandentorren, S.; Oleko, A.; Zaros, C.; Appenzeller, B. M. Hair versus urine for the biomonitoring of pesticide exposure: Results from a pilot cohort study on pregnant women. Environ. Int. 2021, 152, 106481, 10.1016/j.envint.2021.106481
Stekhoven, D. J.; Bühlmann, P. MissForest─non-parametric missing value imputation for mixed-type data. Bioinformatics 2012, 28, 112- 118, 10.1093/bioinformatics/btr597
Bodinier, B. sharp: Stability-enHanced Approaches using Resampling Procedures. R package version 1.3.0, 2022.
Bodinier, B.; Filippi, S.; Nøst, T. H.; Chiquet, J.; Chadeau-Hyam, M. Automated calibration for stability selection in penalised regression and graphical models. J. R. Stat. Soc. C 2023, 72, qlad058
Blondel, V. D.; Guillaume, J.-L.; Lambiotte, R.; Lefebvre, E. Fast unfolding of communities in large networks. J. Stat. Mech.: Theory Exp. 2008, 2008, P10008, 10.1088/1742-5468/2008/10/P10008
Bottolo, L.; Chadeau-Hyam, M.; Hastie, D. I.; Langley, S. R.; Petretto, E.; Tiret, L.; Tregouet, D.; Richardson, S. ESS++: a C++ objected-oriented algorithm for Bayesian stochastic search model exploration. Bioinformatics 2011, 27, 587- 588, 10.1093/bioinformatics/btq684
Bottolo, L.; Chadeau-Hyam, M.; Hastie, D. I.; Zeller, T.; Liquet, B.; Newcombe, P.; Yengo, L.; Wild, P. S.; Schillert, A.; Ziegler, A. GUESS-ing Polygenic Associations with Multiple Phenotypes Using a GPU-Based Evolutionary Stochastic Search Algorithm. PLOS Genet. 2013, 9, e1003657 10.1371/journal.pgen.1003657
Liquet, B.; Bottolo, L.; Campanella, G.; Richardson, S.; Chadeau-Hyam, M. R2GUESS: A Graphics Processing Unit-Based R Package for Bayesian Variable Selection Regression of Multivariate Responses. J. Stat. Software 2016, 69, 1- 32, 10.18637/jss.v069.i02
Chipman, H.; George, E. I.; McCulloch, R. E. Institute of Mathematical Statistics Lecture Notes - Monograph Series; Lecture Notes-Monograph Series; Institute of Mathematical Statistics: Beachwood, OH, 2001, pp 65- 116.
Kass, R. E.; Raftery, A. E. Bayes Factors. J. Am. Stat. Assoc. 1995, 90, 773- 795, 10.1080/01621459.1995.10476572
Zago, A. M.; Faria, N. M. X.; Fávero, J. L.; Meucci, R. D.; Woskie, S.; Fassa, A. G. Pesticide exposure and risk of cardiovascular disease: A systematic review. Glob. Public Health 2022, 17, 3944- 3966, 10.1080/17441692.2020.1808693
Castilla, R.; Asuaje, A.; Rivière, S.; Romero, C. G.; Martín, P.; Cao, G.; Kleiman de Pisarev, D.; Milesi, V.; Alvarez, L. Environmental pollutant hexachlorobenzene induces hypertension in a rat model. Chemosphere 2018, 195, 576- 584, 10.1016/j.chemosphere.2017.11.117
Barber, J. L.; Sweetman, A. J.; van Wijk, D.; Jones, K. C. Hexachlorobenzene in the global environment: Emissions, levels, distribution, trends and processes. Sci. Total Environ. 2005, 349, 1- 44, 10.1016/j.scitotenv.2005.03.014