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1. The role of accelerometer-derived sleep traits on glycated haemoglobin and glucose levels: a Mendelian randomization study

Author

Liu, Junxi, Richmond, Rebecca C., Anderson, Emma L., Bowden, Jack, Barry, Ciarrah-Jane S., Dashti, Hassan S., Daghlas, Iyas S., Lane, Jacqueline M., Kyle, Simon D., Vetter, Céline, Morrison, Claire L., Jones, Samuel E., Wood, Andrew R., Frayling, Timothy M., Wright, Alison K., Carr, Matthew J., Anderson, Simon G., Emsley, Richard A., Ray, David W., Weedon, Michael N., Saxena, Richa, Rutter, Martin K., and Lawlor, Deborah A.

Published
2024
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3. Ultra-processed foods, adiposity and risk of head and neck cancer and oesophageal adenocarcinoma in the European Prospective Investigation into Cancer and Nutrition study: a mediation analysis

Author

Morales-Berstein, Fernanda, Biessy, Carine, Viallon, Vivian, Goncalves-Soares, Ana, Casagrande, Corinne, Hémon, Bertrand, Kliemann, Nathalie, Cairat, Manon, Blanco Lopez, Jessica, Al Nahas, Aline, Chang, Kiara, Vamos, Eszter, Rauber, Fernanda, Bertazzi Levy, Renata, Barbosa Cunha, Diana, Jakszyn, Paula, Ferrari, Pietro, Vineis, Paolo, Masala, Giovanna, Catalano, Alberto, Sonestedt, Emily, Borné, Yan, Katzke, Verena, Bajracharya, Rashmita, Agnoli, Claudia, Guevara, Marcela, Heath, Alicia, Radoï, Loredana, Mancini, Francesca, Weiderpass, Elisabete, Huerta, José María, Sánchez, María-José, Tjønneland, Anne, Kyrø, Cecilie, Schulze, Matthias B., Skeie, Guri, Lukic, Marko, Braaten, Tonje, Gunter, Marc, Millett, Christopher, Agudo, Antonio, Brennan, Paul, Borges, M. Carolina, Richmond, Rebecca C., Richardson, Tom G., Davey Smith, George, Relton, Caroline L., and Huybrechts, Inge

Published
2024
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7. Comprehensive evaluation of smoking exposures and their interactions on DNA methylation

Author

Heijmans, Bastiaan, ’t Hoen, Peter, van Meurs, Joyce, Jansen, Rick, Franke, Lude, Boomsma, Dorret, Pool, René, van Dongen, Jenny, Hottenga, Jouke, van Greevenbroek, Marleen, Stehouwer, Coen, van der Kallen, Carla, Schalkwijk, Casper, Wijmenga, Cisca, Zhernakova, Sasha, Tigchelaar, Ettje, Slagboom, P. Eline, Beekman, Marian, Deelen, Joris, Van Heemst, Diana, Veldink, Jan, van den Berg, Leonard, van Duijn, Cornelia, Hofman, Bert, Isaacs, Aaron, Uitterlinden, André, Jhamai, P. Mila, Verbiest, Michael, Suchiman, H. Eka, Verkerk, Marijn, van der Breggen, Ruud, van Rooij, Jeroen, Lakenberg, Nico, Mei, Hailiang, van Iterson, Maarten, van Galen, Michiel, Bot, Jan, Zhernakova, Dasha, van ‘t Hof, Peter, Deelen, Patrick, Nooren, Irene, Moed, Matthijs, Vermaat, Martijn, Luijk, René, Bonder, Marc, van Dijk, Freerk, Arindrarto, Wibowo, Kielbasa, Szymon, Swertz, Morris, van Zwet, Erik, Hoang, Thanh T., Lee, Yunsung, McCartney, Daniel L., Kersten, Elin T.G., Page, Christian M., Hulls, Paige M., Lee, Mikyeong, Walker, Rosie M., Breeze, Charles E., Bennett, Brian D., Burkholder, Adam B., Ward, James, Brantsæter, Anne Lise, Caspersen, Ida H., Motsinger-Reif, Alison A., Richards, Marie, White, Julie D., Zhao, Shanshan, Richmond, Rebecca C., Magnus, Maria C., Koppelman, Gerard H., Evans, Kathryn L., Marioni, Riccardo E., Håberg, Siri E., and London, Stephanie J.

Published
2024
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8. Genome-wide association studies identify 137 genetic loci for DNA methylation biomarkers of aging

Author

McCartney, Daniel L, Min, Josine L, Richmond, Rebecca C, Lu, Ake T, Sobczyk, Maria K, Davies, Gail, Broer, Linda, Guo, Xiuqing, Jeong, Ayoung, Jung, Jeesun, Kasela, Silva, Katrinli, Seyma, Kuo, Pei-Lun, Matias-Garcia, Pamela R, Mishra, Pashupati P, Nygaard, Marianne, Palviainen, Teemu, Patki, Amit, Raffield, Laura M, Ratliff, Scott M, Richardson, Tom G, Robinson, Oliver, Soerensen, Mette, Sun, Dianjianyi, Tsai, Pei-Chien, van der Zee, Matthijs D, Walker, Rosie M, Wang, Xiaochuan, Wang, Yunzhang, Xia, Rui, Xu, Zongli, Yao, Jie, Zhao, Wei, Correa, Adolfo, Boerwinkle, Eric, Dugué, Pierre-Antoine, Durda, Peter, Elliott, Hannah R, Gieger, Christian, de Geus, Eco JC, Harris, Sarah E, Hemani, Gibran, Imboden, Medea, Kähönen, Mika, Kardia, Sharon LR, Kresovich, Jacob K, Li, Shengxu, Lunetta, Kathryn L, Mangino, Massimo, Mason, Dan, McIntosh, Andrew M, Mengel-From, Jonas, Moore, Ann Zenobia, Murabito, Joanne M, Ollikainen, Miina, Pankow, James S, Pedersen, Nancy L, Peters, Annette, Polidoro, Silvia, Porteous, David J, Raitakari, Olli, Rich, Stephen S, Sandler, Dale P, Sillanpää, Elina, Smith, Alicia K, Southey, Melissa C, Strauch, Konstantin, Tiwari, Hemant, Tanaka, Toshiko, Tillin, Therese, Uitterlinden, Andre G, Van Den Berg, David J, van Dongen, Jenny, Wilson, James G, Wright, John, Yet, Idil, Arnett, Donna, Bandinelli, Stefania, Bell, Jordana T, Binder, Alexandra M, Boomsma, Dorret I, Chen, Wei, Christensen, Kaare, Conneely, Karen N, Elliott, Paul, Ferrucci, Luigi, Fornage, Myriam, Hägg, Sara, Hayward, Caroline, Irvin, Marguerite, Kaprio, Jaakko, Lawlor, Deborah A, Lehtimäki, Terho, Lohoff, Falk W, Milani, Lili, Milne, Roger L, Probst-Hensch, Nicole, Reiner, Alex P, Ritz, Beate, and Rotter, Jerome I

Subjects
Prevention, Nutrition, Aging, Human Genome, Genetics, Generic health relevance, Inflammatory and immune system, Good Health and Well Being, Adiposity, Biomarkers, C-Reactive Protein, CpG Islands, DNA Methylation, Educational Status, Epigenesis, Genetic, Genetic Loci, Genetic Markers, Genome, Human, Genome-Wide Association Study, Granulocytes, Humans, Immunity, Innate, Lipid Metabolism, Multifactorial Inheritance, Plasminogen Activator Inhibitor 1, DNA methylation, GWAS, Epigenetic clock, Genetics of DNA Methylation Consortium, NHLBI Trans-Omics for Precision Medicine (TOPMed) Consortium, Environmental Sciences, Biological Sciences, Information and Computing Sciences, Bioinformatics
Abstract

BackgroundBiological aging estimators derived from DNA methylation data are heritable and correlate with morbidity and mortality. Consequently, identification of genetic and environmental contributors to the variation in these measures in populations has become a major goal in the field.ResultsLeveraging DNA methylation and SNP data from more than 40,000 individuals, we identify 137 genome-wide significant loci, of which 113 are novel, from genome-wide association study (GWAS) meta-analyses of four epigenetic clocks and epigenetic surrogate markers for granulocyte proportions and plasminogen activator inhibitor 1 levels, respectively. We find evidence for shared genetic loci associated with the Horvath clock and expression of transcripts encoding genes linked to lipid metabolism and immune function. Notably, these loci are independent of those reported to regulate DNA methylation levels at constituent clock CpGs. A polygenic score for GrimAge acceleration showed strong associations with adiposity-related traits, educational attainment, parental longevity, and C-reactive protein levels.ConclusionThis study illuminates the genetic architecture underlying epigenetic aging and its shared genetic contributions with lifestyle factors and longevity.

Published
2021

9. Genome-wide association analyses of physical activity and sedentary behavior provide insights into underlying mechanisms and roles in disease prevention

Author

Wang, Zhe, Emmerich, Andrew, Pillon, Nicolas J., Moore, Tim, Hemerich, Daiane, Cornelis, Marilyn C., Mazzaferro, Eugenia, Broos, Siacia, Ahluwalia, Tarunveer S., Bartz, Traci M., Bentley, Amy R., Bielak, Lawrence F., Chong, Mike, Chu, Audrey Y., Berry, Diane, Dorajoo, Rajkumar, Dueker, Nicole D., Kasbohm, Elisa, Feenstra, Bjarke, Feitosa, Mary F., Gieger, Christian, Graff, Mariaelisa, Hall, Leanne M., Haller, Toomas, Hartwig, Fernando P., Hillis, David A., Huikari, Ville, Heard-Costa, Nancy, Holzapfel, Christina, Jackson, Anne U., Johansson, Åsa, Jørgensen, Anja Moltke, Kaakinen, Marika A., Karlsson, Robert, Kerr, Kathleen F., Kim, Boram, Koolhaas, Chantal M., Kutalik, Zoltan, Lagou, Vasiliki, Lind, Penelope A., Lorentzon, Mattias, Lyytikäinen, Leo-Pekka, Mangino, Massimo, Metzendorf, Christoph, Monroe, Kristine R., Pacolet, Alexander, Pérusse, Louis, Pool, Rene, Richmond, Rebecca C., Rivera, Natalia V., Robiou-du-Pont, Sebastien, Schraut, Katharina E., Schulz, Christina-Alexandra, Stringham, Heather M., Tanaka, Toshiko, Teumer, Alexander, Turman, Constance, van der Most, Peter J., Vanmunster, Mathias, van Rooij, Frank J. A., van Vliet-Ostaptchouk, Jana V., Zhang, Xiaoshuai, Zhao, Jing-Hua, Zhao, Wei, Balkhiyarova, Zhanna, Balslev-Harder, Marie N., Baumeister, Sebastian E., Beilby, John, Blangero, John, Boomsma, Dorret I., Brage, Soren, Braund, Peter S., Brody, Jennifer A., Bruinenberg, Marcel, Ekelund, Ulf, Liu, Ching-Ti, Cole, John W., Collins, Francis S., Cupples, L. Adrienne, Esko, Tõnu, Enroth, Stefan, Faul, Jessica D., Fernandez-Rhodes, Lindsay, Fohner, Alison E., Franco, Oscar H., Galesloot, Tessel E., Gordon, Scott D., Grarup, Niels, Hartman, Catharina A., Heiss, Gerardo, Hui, Jennie, Illig, Thomas, Jago, Russell, James, Alan, Joshi, Peter K., Jung, Taeyeong, Kähönen, Mika, Kilpeläinen, Tuomas O., Koh, Woon-Puay, Kolcic, Ivana, Kraft, Peter P., Kuusisto, Johanna, Launer, Lenore J., Li, Aihua, Linneberg, Allan, Luan, Jian’an, Vidal, Pedro Marques, Medland, Sarah E., Milaneschi, Yuri, Moscati, Arden, Musk, Bill, Nelson, Christopher P., Nolte, Ilja M., Pedersen, Nancy L., Peters, Annette, Peyser, Patricia A., Power, Christine, Raitakari, Olli T., Reedik, Mägi, Reiner, Alex P., Ridker, Paul M., Rudan, Igor, Ryan, Kathy, Sarzynski, Mark A., Scott, Laura J., Scott, Robert A., Sidney, Stephen, Siggeirsdottir, Kristin, Smith, Albert V., Smith, Jennifer A., Sonestedt, Emily, Strøm, Marin, Tai, E. Shyong, Teo, Koon K., Thorand, Barbara, Tönjes, Anke, Tremblay, Angelo, Uitterlinden, Andre G., Vangipurapu, Jagadish, van Schoor, Natasja, Völker, Uwe, Willemsen, Gonneke, Williams, Kayleen, Wong, Quenna, Xu, Huichun, Young, Kristin L., Yuan, Jian Min, Zillikens, M. Carola, Zonderman, Alan B., Ameur, Adam, Bandinelli, Stefania, Bis, Joshua C., Boehnke, Michael, Bouchard, Claude, Chasman, Daniel I., Smith, George Davey, de Geus, Eco J. C., Deldicque, Louise, Dörr, Marcus, Evans, Michele K., Ferrucci, Luigi, Fornage, Myriam, Fox, Caroline, Garland, Jr, Theodore, Gudnason, Vilmundur, Gyllensten, Ulf, Hansen, Torben, Hayward, Caroline, Horta, Bernardo L., Hyppönen, Elina, Jarvelin, Marjo-Riitta, Johnson, W. Craig, Kardia, Sharon L. R., Kiemeney, Lambertus A., Laakso, Markku, Langenberg, Claudia, Lehtimäki, Terho, Marchand, Loic Le, Magnusson, Patrik K. E., Martin, Nicholas G., Melbye, Mads, Metspalu, Andres, Meyre, David, North, Kari E., Ohlsson, Claes, Oldehinkel, Albertine J., Orho-Melander, Marju, Pare, Guillaume, Park, Taesung, Pedersen, Oluf, Penninx, Brenda W. J. H., Pers, Tune H., Polasek, Ozren, Prokopenko, Inga, Rotimi, Charles N., Samani, Nilesh J., Sim, Xueling, Snieder, Harold, Sørensen, Thorkild I. A., Spector, Tim D., Timpson, Nicholas J., van Dam, Rob M., van der Velde, Nathalie, van Duijn, Cornelia M., Vollenweider, Peter, Völzke, Henry, Voortman, Trudy, Waeber, Gérard, Wareham, Nicholas J., Weir, David R., Wichmann, Heinz-Erich, Wilson, James F., Hevener, Andrea L., Krook, Anna, Zierath, Juleen R., Thomis, Martine A. I., Loos, Ruth J. F., and Hoed, Marcel den

Published
2022
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23. Applying Mendelian randomization to appraise causality in relationships between nutrition and cancer

Author

Wade, Kaitlin H., Yarmolinsky, James, Giovannucci, Edward, Lewis, Sarah J., Millwood, Iona Y., Munafò, Marcus R., Meddens, Fleur, Burrows, Kimberley, Bell, Joshua A., Davies, Neil M., Mariosa, Daniela, Kanerva, Noora, Vincent, Emma E., Smith-Byrne, Karl, Guida, Florence, Gunter, Marc J., Sanderson, Eleanor, Dudbridge, Frank, Burgess, Stephen, Cornelis, Marilyn C., Richardson, Tom G., Borges, Maria Carolina, Bowden, Jack, Hemani, Gibran, Cho, Yoonsu, Spiller, Wes, Richmond, Rebecca C., Carter, Alice R., Langdon, Ryan, Lawlor, Deborah A., Walters, Robin G., Vimaleswaran, Karani Santhanakrishnan, Anderson, Annie, Sandu, Meda R., Tilling, Kate, Davey Smith, George, Martin, Richard M., and Relton, Caroline L.

Published
2022
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24. Maternal and fetal genetic effects on birth weight and their relevance to cardio-metabolic risk factors

Author

Warrington, Nicole M, Beaumont, Robin N, Horikoshi, Momoko, Day, Felix R, Helgeland, Øyvind, Laurin, Charles, Bacelis, Jonas, Peng, Shouneng, Hao, Ke, Feenstra, Bjarke, Wood, Andrew R, Mahajan, Anubha, Tyrrell, Jessica, Robertson, Neil R, Rayner, N William, Qiao, Zhen, Moen, Gunn-Helen, Vaudel, Marc, Marsit, Carmen J, Chen, Jia, Nodzenski, Michael, Schnurr, Theresia M, Zafarmand, Mohammad H, Bradfield, Jonathan P, Grarup, Niels, Kooijman, Marjolein N, Li-Gao, Ruifang, Geller, Frank, Ahluwalia, Tarunveer S, Paternoster, Lavinia, Rueedi, Rico, Huikari, Ville, Hottenga, Jouke-Jan, Lyytikäinen, Leo-Pekka, Cavadino, Alana, Metrustry, Sarah, Cousminer, Diana L, Wu, Ying, Thiering, Elisabeth, Wang, Carol A, Have, Christian T, Vilor-Tejedor, Natalia, Joshi, Peter K, Painter, Jodie N, Ntalla, Ioanna, Myhre, Ronny, Pitkänen, Niina, van Leeuwen, Elisabeth M, Joro, Raimo, Lagou, Vasiliki, Richmond, Rebecca C, Espinosa, Ana, Barton, Sheila J, Inskip, Hazel M, Holloway, John W, Santa-Marina, Loreto, Estivill, Xavier, Ang, Wei, Marsh, Julie A, Reichetzeder, Christoph, Marullo, Letizia, Hocher, Berthold, Lunetta, Kathryn L, Murabito, Joanne M, Relton, Caroline L, Kogevinas, Manolis, Chatzi, Leda, Allard, Catherine, Bouchard, Luigi, Hivert, Marie-France, Zhang, Ge, Muglia, Louis J, Heikkinen, Jani, Morgen, Camilla S, van Kampen, Antoine HC, van Schaik, Barbera DC, Mentch, Frank D, Langenberg, Claudia, Luan, Jian’an, Scott, Robert A, Zhao, Jing Hua, Hemani, Gibran, Ring, Susan M, Bennett, Amanda J, Gaulton, Kyle J, Fernandez-Tajes, Juan, van Zuydam, Natalie R, Medina-Gomez, Carolina, de Haan, Hugoline G, Rosendaal, Frits R, Kutalik, Zoltán, Marques-Vidal, Pedro, Das, Shikta, Willemsen, Gonneke, Mbarek, Hamdi, Müller-Nurasyid, Martina, Standl, Marie, Appel, Emil VR, Fonvig, Cilius E, and Trier, Caecilie

Subjects
Biological Sciences, Genetics, Cardiovascular, Perinatal Period - Conditions Originating in Perinatal Period, Nutrition, Prevention, Preterm, Low Birth Weight and Health of the Newborn, Pediatric, Obesity, Conditions Affecting the Embryonic and Fetal Periods, Infant Mortality, 2.1 Biological and endogenous factors, Aetiology, Reproductive health and childbirth, Good Health and Well Being, Adult, Birth Weight, Blood Pressure, Body Height, Diabetes Mellitus, Type 2, Female, Fetal Development, Genetic Predisposition to Disease, Genome-Wide Association Study, Heart Diseases, Humans, Infant, Newborn, Male, Maternal Inheritance, Maternal-Fetal Exchange, Metabolic Diseases, Models, Genetic, Polymorphism, Single Nucleotide, Pregnancy, Risk Factors, EGG Consortium, Medical and Health Sciences, Developmental Biology, Agricultural biotechnology, Bioinformatics and computational biology
Abstract

Birth weight variation is influenced by fetal and maternal genetic and non-genetic factors, and has been reproducibly associated with future cardio-metabolic health outcomes. In expanded genome-wide association analyses of own birth weight (n = 321,223) and offspring birth weight (n = 230,069 mothers), we identified 190 independent association signals (129 of which are novel). We used structural equation modeling to decompose the contributions of direct fetal and indirect maternal genetic effects, then applied Mendelian randomization to illuminate causal pathways. For example, both indirect maternal and direct fetal genetic effects drive the observational relationship between lower birth weight and higher later blood pressure: maternal blood pressure-raising alleles reduce offspring birth weight, but only direct fetal effects of these alleles, once inherited, increase later offspring blood pressure. Using maternal birth weight-lowering genotypes to proxy for an adverse intrauterine environment provided no evidence that it causally raises offspring blood pressure, indicating that the inverse birth weight-blood pressure association is attributable to genetic effects, and not to intrauterine programming.

Published
2019

26. Investigating the effect of sexual behaviour on oropharyngeal cancer risk: a methodological assessment of Mendelian randomization

Author

Gormley, Mark, Dudding, Tom, Kachuri, Linda, Burrows, Kimberley, Chong, Amanda H. W., Martin, Richard M., Thomas, Steven J., Tyrrell, Jessica, Ness, Andrew R., Brennan, Paul, Munafò, Marcus R., Pring, Miranda, Boccia, Stefania, Olshan, Andrew F., Diergaarde, Brenda, Hung, Rayjean J., Liu, Geoffrey, Tajara, Eloiza H., Severino, Patricia, Toporcov, Tatiana N., Lacko, Martin, Waterboer, Tim, Brenner, Nicole, Smith, George Davey, Vincent, Emma E., and Richmond, Rebecca C.

Published
2022
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27. Exploring the causal effect of maternal pregnancy adiposity on offspring adiposity: Mendelian randomisation using polygenic risk scores

Author

Bond, Tom A., Richmond, Rebecca C., Karhunen, Ville, Cuellar-Partida, Gabriel, Borges, Maria Carolina, Zuber, Verena, Couto Alves, Alexessander, Mason, Dan, Yang, Tiffany C., Gunter, Marc J., Dehghan, Abbas, Tzoulaki, Ioanna, Sebert, Sylvain, Evans, David M., Lewin, Alex M., O’Reilly, Paul F., Lawlor, Deborah A., and Järvelin, Marjo-Riitta

Published
2022
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28. Longitudinal associations of DNA methylation and sleep in children: a meta-analysis

Author

Sammallahti, Sara, Koopman-Verhoeff, M. Elisabeth, Binter, Anne-Claire, Mulder, Rosa H., Cabré-Riera, Alba, Kvist, Tuomas, Malmberg, Anni L. K., Pesce, Giancarlo, Plancoulaine, Sabine, Heiss, Jonathan A., Rifas-Shiman, Sheryl L., Röder, Stefan W., Starling, Anne P., Wilson, Rory, Guerlich, Kathrin, Haftorn, Kristine L., Page, Christian M., Luik, Annemarie I., Tiemeier, Henning, Felix, Janine F., Raikkonen, Katri, Lahti, Jari, Relton, Caroline L., Sharp, Gemma C., Waldenberger, Melanie, Grote, Veit, Heude, Barbara, Annesi-Maesano, Isabella, Hivert, Marie-France, Zenclussen, Ana C., Herberth, Gunda, Dabelea, Dana, Grazuleviciene, Regina, Vafeiadi, Marina, Håberg, Siri E., London, Stephanie J., Guxens, Mònica, Richmond, Rebecca C., and Cecil, Charlotte A. M.

Published
2022
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32. The effects of daylight saving time clock changes on accelerometer‐measured sleep duration in the UK Biobank.

Author

Lange, Melanie A., Richmond, Rebecca C., Birnie, Kate, Shapland, Chin Yang, Tilling, Kate, and Davies, Neil M.

Abstract

Summary We explored the effects of daylight saving time clock changes on sleep duration in a large accelerometer dataset. Our sample included UK Biobank participants (n = 11,780; aged 43–78 years) with accelerometer data for one or more days during the 2 weeks surrounding the Spring and Autumn daylight saving time transitions from October 2013 and November 2015. Between‐individual t‐tests compared sleep duration on the Sunday (midnight to midnight) of the clock changes with the Sunday before and the Sunday after. We also compared sleep duration on all other days (Monday–Saturday) before and after the clock changes. In Spring, mean sleep duration was 65 min lower on the Sunday of the clock changes than the Sunday before (95% confidence interval −72 to −58 min), and 61 min lower than the Sunday after (95% confidence interval −69 to −53). In Autumn, the mean sleep duration on the Sunday of the clock changes was 33 min higher than the Sunday before (95% confidence interval 27–39 min), and 38 min higher than the Sunday after (95% confidence interval 32–43 min). There was some evidence of catch‐up sleep after both transitions, with sleep duration a little higher on the Monday–Friday than before, although this was less pronounced in Autumn. Future research should use large datasets with longer periods of accelerometer wear to capture sleep duration before and after the transition in the same individuals, and examine other aspects of sleep such as circadian misalignment, sleep fragmentation or daytime napping. [ABSTRACT FROM AUTHOR]

Published
2024
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35. Epigenetic timing effects on child developmental outcomes: A longitudinal meta-regression of findings from the Pregnancy And Childhood Epigenetics Consortium

Author

Neumann, Alexander, primary, Sammallahti, Sara, additional, Cosin-Tomas, Marta, additional, Reese, Sarah E, additional, Suderman, Matthew, additional, Alemany, Silvia, additional, Almqvist, Catarina, additional, Andrusaityte, Sandra, additional, Arshad, Syed H, additional, Bakermans-Kranenburg, Marian J, additional, Beilin, Lawrence, additional, Breton, Carrie, additional, Bustamante, Mariona, additional, Czamara, Darina, additional, Dabelea, Dana, additional, Eng, Celeste, additional, Eskenazi, Brenda, additional, Fuemmeler, Bernard F, additional, Gilliland, Frank D, additional, Grazuleviciene, Regina, additional, Håberg, Siri E, additional, Herberth, Gunda, additional, Holland, Nina, additional, Hough, Amy, additional, Hu, Donglei, additional, Huen, Karen, additional, Hüls, Anke, additional, Jin, Jianping, additional, Julvez, Jordi, additional, Koletzko, Berthold V, additional, Koppelman, Gerard H, additional, Kull, Inger, additional, Lu, Xueling, additional, Maitre, Léa, additional, Mason, Dan, additional, Mélen, Erik, additional, Merid, Simon K, additional, Molloy, Peter L, additional, Mori, Trevor A, additional, Mulder, Rosa H, additional, Page, Christian M, additional, Richmond, Rebecca C, additional, Roder, Stefan, additional, Ross, Jason P, additional, Schellhas, Laura, additional, Sebert, Sylvain, additional, Sheppard, Dean, additional, Snieder, Harold, additional, Starling, Anne P, additional, Stein, Dan J, additional, Tindula, Gwen, additional, van IJzendoorn, Marinus H, additional, Vonk, Judith, additional, Walton, Esther, additional, Witonsky, Jonathan, additional, Xu, Cheng-Jian, additional, Yang, Ivana V, additional, Yousefi, Paul D, additional, Zar, Heather J, additional, Zenclussen, Ana C, additional, Zhang, Hongmei, additional, Tiemeier, Henning, additional, London, Stephanie J, additional, Felix, Janine F, additional, and Cecil, Charlotte, additional

Published
2024
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37. Comprehensive evaluation of smoking exposures and their interactions on DNA methylation

Author

Hoang, Thanh T., primary, Lee, Yunsung, additional, McCartney, Daniel L., additional, Kersten, Elin T.G., additional, Page, Christian M., additional, Hulls, Paige M., additional, Lee, Mikyeong, additional, Walker, Rosie M., additional, Breeze, Charles E., additional, Bennett, Brian D., additional, Burkholder, Adam B., additional, Ward, James, additional, Brantsæter, Anne Lise, additional, Caspersen, Ida H., additional, Motsinger-Reif, Alison A., additional, Richards, Marie, additional, White, Julie D., additional, Zhao, Shanshan, additional, Richmond, Rebecca C., additional, Magnus, Maria C., additional, Koppelman, Gerard H., additional, Evans, Kathryn L., additional, Marioni, Riccardo E., additional, Håberg, Siri E., additional, London, Stephanie J., additional, Heijmans, Bastiaan, additional, ’t Hoen, Peter, additional, van Meurs, Joyce, additional, Jansen, Rick, additional, Franke, Lude, additional, Boomsma, Dorret, additional, Pool, René, additional, van Dongen, Jenny, additional, Hottenga, Jouke, additional, van Greevenbroek, Marleen, additional, Stehouwer, Coen, additional, van der Kallen, Carla, additional, Schalkwijk, Casper, additional, Wijmenga, Cisca, additional, Zhernakova, Sasha, additional, Tigchelaar, Ettje, additional, Slagboom, P. Eline, additional, Beekman, Marian, additional, Deelen, Joris, additional, Van Heemst, Diana, additional, Veldink, Jan, additional, van den Berg, Leonard, additional, van Duijn, Cornelia, additional, Hofman, Bert, additional, Isaacs, Aaron, additional, Uitterlinden, André, additional, Jhamai, P. Mila, additional, Verbiest, Michael, additional, Suchiman, H. Eka, additional, Verkerk, Marijn, additional, van der Breggen, Ruud, additional, van Rooij, Jeroen, additional, Lakenberg, Nico, additional, Mei, Hailiang, additional, van Iterson, Maarten, additional, van Galen, Michiel, additional, Bot, Jan, additional, Zhernakova, Dasha, additional, van ‘t Hof, Peter, additional, Deelen, Patrick, additional, Nooren, Irene, additional, Moed, Matthijs, additional, Vermaat, Martijn, additional, Luijk, René, additional, Bonder, Marc, additional, van Dijk, Freerk, additional, Arindrarto, Wibowo, additional, Kielbasa, Szymon, additional, Swertz, Morris, additional, and van Zwet, Erik, additional

Published
2024
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38. Maternal BMI at the start of pregnancy and offspring epigenome-wide DNA methylation: findings from the pregnancy and childhood epigenetics (PACE) consortium

Author

Sharp, Gemma C, Salas, Lucas A, Monnereau, Claire, Allard, Catherine, Yousefi, Paul, Everson, Todd M, Bohlin, Jon, Xu, Zongli, Huang, Rae-Chi, Reese, Sarah E, Xu, Cheng-Jian, Baïz, Nour, Hoyo, Cathrine, Agha, Golareh, Roy, Ritu, Holloway, John W, Ghantous, Akram, Merid, Simon K, Bakulski, Kelly M, Küpers, Leanne K, Zhang, Hongmei, Richmond, Rebecca C, Page, Christian M, Duijts, Liesbeth, Lie, Rolv T, Melton, Phillip E, Vonk, Judith M, Nohr, Ellen A, Williams-DeVane, ClarLynda, Huen, Karen, Rifas-Shiman, Sheryl L, Ruiz-Arenas, Carlos, Gonseth, Semira, Rezwan, Faisal I, Herceg, Zdenko, Ekström, Sandra, Croen, Lisa, Falahi, Fahimeh, Perron, Patrice, Karagas, Margaret R, Quraishi, Bilal M, Suderman, Matthew, Magnus, Maria C, Jaddoe, Vincent WV, Taylor, Jack A, Anderson, Denise, Zhao, Shanshan, Smit, Henriette A, Josey, Michele J, Bradman, Asa, Baccarelli, Andrea A, Bustamante, Mariona, Håberg, Siri E, Pershagen, Göran, Hertz-Picciotto, Irva, Newschaffer, Craig, Corpeleijn, Eva, Bouchard, Luigi, Lawlor, Debbie A, Maguire, Rachel L, Barcellos, Lisa F, Smith, George Davey, Eskenazi, Brenda, Karmaus, Wilfried, Marsit, Carmen J, Hivert, Marie-France, Snieder, Harold, Fallin, M Daniele, Melén, Erik, Munthe-Kaas, Monica C, Arshad, Hasan, Wiemels, Joseph L, Annesi-Maesano, Isabella, Vrijheid, Martine, Oken, Emily, Holland, Nina, Murphy, Susan K, Sørensen, Thorkild IA, Koppelman, Gerard H, Newnham, John P, Wilcox, Allen J, Nystad, Wenche, London, Stephanie J, Felix, Janine F, and Relton, Caroline L

Subjects
Biological Sciences, Genetics, Perinatal Period - Conditions Originating in Perinatal Period, Contraception/Reproduction, Pediatric, Human Genome, Obesity, 2.1 Biological and endogenous factors, Aetiology, Reproductive health and childbirth, Adult, Body Mass Index, Cohort Studies, DNA Methylation, Epigenesis, Genetic, Epigenomics, Female, Humans, Infant, Newborn, Male, Maternal Inheritance, Mothers, Pregnancy, Pregnancy Outcome, Prenatal Exposure Delayed Effects, Medical and Health Sciences, Genetics & Heredity
Abstract

Pre-pregnancy maternal obesity is associated with adverse offspring outcomes at birth and later in life. Individual studies have shown that epigenetic modifications such as DNA methylation could contribute. Within the Pregnancy and Childhood Epigenetics (PACE) Consortium, we meta-analysed the association between pre-pregnancy maternal BMI and methylation at over 450,000 sites in newborn blood DNA, across 19 cohorts (9,340 mother-newborn pairs). We attempted to infer causality by comparing the effects of maternal versus paternal BMI and incorporating genetic variation. In four additional cohorts (1,817 mother-child pairs), we meta-analysed the association between maternal BMI at the start of pregnancy and blood methylation in adolescents. In newborns, maternal BMI was associated with small (

Published
2017

40. Integrating multiple lines of evidence to assess the effects of maternal BMI on pregnancy and perinatal outcomes

Author

Borges, Maria Carolina, Clayton, Gemma L., Freathy, Rachel M., Felix, Janine F., Fernández-Sanlés, Alba, Soares, Ana Gonçalves, Kilpi, Fanny, Yang, Qian, McEachan, Rosemary R.C., Richmond, Rebecca C., Liu, Xueping, Skotte, Line, Irizar, Amaia, Hattersley, Andrew T., Bodinier, Barbara, Scholtens, Denise M., Nohr, Ellen A., Bond, Tom A., Hayes, M. Geoffrey, West, Jane, Tyrrell, Jessica, Wright, John, Bouchard, Luigi, Murcia, Mario, Bustamante, Mariona, Chadeau-Hyam, Marc, Jarvelin, Marjo Riitta, Vrijheid, Martine, Perron, Patrice, Magnus, Per, Gaillard, Romy, Jaddoe, Vincent W.V., Lowe, William L., Feenstra, Bjarke, Hivert, Marie France, Sørensen, Thorkild I.A., Håberg, Siri E., Serbert, Sylvain, Magnus, Maria, Lawlor, Deborah A., Borges, Maria Carolina, Clayton, Gemma L., Freathy, Rachel M., Felix, Janine F., Fernández-Sanlés, Alba, Soares, Ana Gonçalves, Kilpi, Fanny, Yang, Qian, McEachan, Rosemary R.C., Richmond, Rebecca C., Liu, Xueping, Skotte, Line, Irizar, Amaia, Hattersley, Andrew T., Bodinier, Barbara, Scholtens, Denise M., Nohr, Ellen A., Bond, Tom A., Hayes, M. Geoffrey, West, Jane, Tyrrell, Jessica, Wright, John, Bouchard, Luigi, Murcia, Mario, Bustamante, Mariona, Chadeau-Hyam, Marc, Jarvelin, Marjo Riitta, Vrijheid, Martine, Perron, Patrice, Magnus, Per, Gaillard, Romy, Jaddoe, Vincent W.V., Lowe, William L., Feenstra, Bjarke, Hivert, Marie France, Sørensen, Thorkild I.A., Håberg, Siri E., Serbert, Sylvain, Magnus, Maria, and Lawlor, Deborah A.

Abstract

Background: Higher maternal pre-pregnancy body mass index (BMI) is associated with adverse pregnancy and perinatal outcomes. However, whether these associations are causal remains unclear. Methods: We explored the relation of maternal pre-/early-pregnancy BMI with 20 pregnancy and perinatal outcomes by integrating evidence from three different approaches (i.e. multivariable regression, Mendelian randomisation, and paternal negative control analyses), including data from over 400,000 women. Results: All three analytical approaches supported associations of higher maternal BMI with lower odds of maternal anaemia, delivering a small-for-gestational-age baby and initiating breastfeeding, but higher odds of hypertensive disorders of pregnancy, gestational hypertension, preeclampsia, gestational diabetes, pre-labour membrane rupture, induction of labour, caesarean section, large-for-gestational age, high birthweight, low Apgar score at 1 min, and neonatal intensive care unit admission. For example, higher maternal BMI was associated with higher risk of gestational hypertension in multivariable regression (OR = 1.67; 95% CI = 1.63, 1.70 per standard unit in BMI) and Mendelian randomisation (OR = 1.59; 95% CI = 1.38, 1.83), which was not seen for paternal BMI (OR = 1.01; 95% CI = 0.98, 1.04). Findings did not support a relation between maternal BMI and perinatal depression. For other outcomes, evidence was inconclusive due to inconsistencies across the applied approaches or substantial imprecision in effect estimates from Mendelian randomisation. Conclusions: Our findings support a causal role for maternal pre-/early-pregnancy BMI on 14 out of 20 adverse pregnancy and perinatal outcomes. Pre-conception interventions to support women maintaining a healthy BMI may reduce the burden of obstetric and neonatal complications. Funding: Medical Research Council, British Heart Founda

Published
2024

41. Ultra-processed foods, adiposity and risk of head and neck cancer and oesophageal adenocarcinoma in the European Prospective Investigation into Cancer and Nutrition study:a mediation analysis

Author

Morales-Berstein, Fernanda, Biessy, Carine, Viallon, Vivian, Goncalves-Soares, Ana, Casagrande, Corinne, Hémon, Bertrand, Kliemann, Nathalie, Cairat, Manon, Blanco Lopez, Jessica, Al Nahas, Aline, Chang, Kiara, Vamos, Eszter, Rauber, Fernanda, Bertazzi Levy, Renata, Barbosa Cunha, Diana, Jakszyn, Paula, Ferrari, Pietro, Vineis, Paolo, Masala, Giovanna, Catalano, Alberto, Sonestedt, Emily, Borné, Yan, Katzke, Verena, Bajracharya, Rashmita, Agnoli, Claudia, Guevara, Marcela, Heath, Alicia, Radoï, Loredana, Mancini, Francesca, Weiderpass, Elisabete, Huerta, José María, Sánchez, María-José, Tjønneland, Anne, Kyrø, Cecilie, Schulze, Matthias B, Skeie, Guri, Lukic, Marko, Braaten, Tonje, Gunter, Marc, Millett, Christopher, Agudo, Antonio, Brennan, Paul, Borges, M Carolina, Richmond, Rebecca C, Richardson, Tom G, Davey Smith, George, Relton, Caroline L, Huybrechts, Inge, Morales-Berstein, Fernanda, Biessy, Carine, Viallon, Vivian, Goncalves-Soares, Ana, Casagrande, Corinne, Hémon, Bertrand, Kliemann, Nathalie, Cairat, Manon, Blanco Lopez, Jessica, Al Nahas, Aline, Chang, Kiara, Vamos, Eszter, Rauber, Fernanda, Bertazzi Levy, Renata, Barbosa Cunha, Diana, Jakszyn, Paula, Ferrari, Pietro, Vineis, Paolo, Masala, Giovanna, Catalano, Alberto, Sonestedt, Emily, Borné, Yan, Katzke, Verena, Bajracharya, Rashmita, Agnoli, Claudia, Guevara, Marcela, Heath, Alicia, Radoï, Loredana, Mancini, Francesca, Weiderpass, Elisabete, Huerta, José María, Sánchez, María-José, Tjønneland, Anne, Kyrø, Cecilie, Schulze, Matthias B, Skeie, Guri, Lukic, Marko, Braaten, Tonje, Gunter, Marc, Millett, Christopher, Agudo, Antonio, Brennan, Paul, Borges, M Carolina, Richmond, Rebecca C, Richardson, Tom G, Davey Smith, George, Relton, Caroline L, and Huybrechts, Inge

Abstract

Objectives The risk of suicidal behavior after discharge from psychiatric admission is high. The aim of this study was to examine whether the SAFE intervention, an implementation of a systematic safer discharge procedure, was associated with a reduction in suicidal behavior after discharge. Methods The SAFE intervention was implemented at Mental Health Center Copenhagen in March 2018 and consisted of three systematic discharge procedures: (1) A face-to-face meeting between patient and outpatient staff prior to discharge, (2) A face-to-face meeting within the first week after discharge, and (3) Involvement of relatives. Risk of suicide attempt at six-month post-discharge among patients discharged from the SAFE intervention was compared with patients discharged from comparison mental health centers using propensity score matching. Results 7604 discharges took place at the intervention site, which were 1:1 matched with discharges from comparison sites. During the six months of follow-up, a total of 570 suicide attempts and 25 suicides occurred. The rate of suicide attempt was 11,652 per 100,000 person-years at the SAFE site, while it was 10,530 at comparisons sites. No observable difference in suicide attempt 1.10 (95% CI: 0.89–1.35) or death by suicide (OR = 1.27; 95% CI:0.58–2.81) was found between sites at 6-month follow-up. Conclusion No difference in suicidal behavior between the sites was found in this pragmatic study. High rates of suicidal behavior were found during the 6-months discharge period, which could suggest that a preventive intervention should include support over a longer post-discharge period than the one-week follow-up offered in the SAFE intervention., PURPOSE: To investigate the role of adiposity in the associations between ultra-processed food (UPF) consumption and head and neck cancer (HNC) and oesophageal adenocarcinoma (OAC) in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort.METHODS: Our study included 450,111 EPIC participants. We used Cox regressions to investigate the associations between the consumption of UPFs and HNC and OAC risk. A mediation analysis was performed to assess the role of body mass index (BMI) and waist-to-hip ratio (WHR) in these associations. In sensitivity analyses, we investigated accidental death as a negative control outcome.RESULTS: During a mean follow-up of 14.13 ± 3.98 years, 910 and 215 participants developed HNC and OAC, respectively. A 10% g/d higher consumption of UPFs was associated with an increased risk of HNC (hazard ratio [HR] = 1.23, 95% confidence interval [CI] 1.14-1.34) and OAC (HR = 1.24, 95% CI 1.05-1.47). WHR mediated 5% (95% CI 3-10%) of the association between the consumption of UPFs and HNC risk, while BMI and WHR, respectively, mediated 13% (95% CI 6-53%) and 15% (95% CI 8-72%) of the association between the consumption of UPFs and OAC risk. UPF consumption was positively associated with accidental death in the negative control analysis.CONCLUSIONS: We reaffirmed that higher UPF consumption is associated with greater risk of HNC and OAC in EPIC. The proportion mediated via adiposity was small. Further research is required to investigate other mechanisms that may be at play (if there is indeed any causal effect of UPF consumption on these cancers).

Published
2024

42. DNA Methylation in Newborns and Maternal Smoking in Pregnancy: Genome-wide Consortium Meta-analysis

Author

Joubert, Bonnie R, Felix, Janine F, Yousefi, Paul, Bakulski, Kelly M, Just, Allan C, Breton, Carrie, Reese, Sarah E, Markunas, Christina A, Richmond, Rebecca C, Xu, Cheng-Jian, Küpers, Leanne K, Oh, Sam S, Hoyo, Cathrine, Gruzieva, Olena, Söderhäll, Cilla, Salas, Lucas A, Baïz, Nour, Zhang, Hongmei, Lepeule, Johanna, Ruiz, Carlos, Ligthart, Symen, Wang, Tianyuan, Taylor, Jack A, Duijts, Liesbeth, Sharp, Gemma C, Jankipersadsing, Soesma A, Nilsen, Roy M, Vaez, Ahmad, Fallin, M Daniele, Hu, Donglei, Litonjua, Augusto A, Fuemmeler, Bernard F, Huen, Karen, Kere, Juha, Kull, Inger, Munthe-Kaas, Monica Cheng, Gehring, Ulrike, Bustamante, Mariona, Saurel-Coubizolles, Marie José, Quraishi, Bilal M, Ren, Jie, Tost, Jörg, Gonzalez, Juan R, Peters, Marjolein J, Håberg, Siri E, Xu, Zongli, van Meurs, Joyce B, Gaunt, Tom R, Kerkhof, Marjan, Corpeleijn, Eva, Feinberg, Andrew P, Eng, Celeste, Baccarelli, Andrea A, Neelon, Sara E Benjamin, Bradman, Asa, Merid, Simon Kebede, Bergström, Anna, Herceg, Zdenko, Hernandez-Vargas, Hector, Brunekreef, Bert, Pinart, Mariona, Heude, Barbara, Ewart, Susan, Yao, Jin, Lemonnier, Nathanaël, Franco, Oscar H, Wu, Michael C, Hofman, Albert, McArdle, Wendy, Van der Vlies, Pieter, Falahi, Fahimeh, Gillman, Matthew W, Barcellos, Lisa F, Kumar, Ashish, Wickman, Magnus, Guerra, Stefano, Charles, Marie-Aline, Holloway, John, Auffray, Charles, Tiemeier, Henning W, Smith, George Davey, Postma, Dirkje, Hivert, Marie-France, Eskenazi, Brenda, Vrijheid, Martine, Arshad, Hasan, Antó, Josep M, Dehghan, Abbas, Karmaus, Wilfried, Annesi-Maesano, Isabella, Sunyer, Jordi, Ghantous, Akram, Pershagen, Göran, Holland, Nina, Murphy, Susan K, DeMeo, Dawn L, Burchard, Esteban G, Ladd-Acosta, Christine, Snieder, Harold, and Nystad, Wenche

Subjects
Genetics, Pediatric, Human Genome, Tobacco, Tobacco Smoke and Health, Prevention, Aetiology, 2.1 Biological and endogenous factors, 2.2 Factors relating to the physical environment, Respiratory, Reproductive health and childbirth, Good Health and Well Being, Asthma, Child, Child, Preschool, Chromosome Mapping, Cleft Lip, Cleft Palate, DNA Methylation, Epigenesis, Genetic, Female, Genetic Association Studies, Humans, Infant, Infant, Newborn, Pregnancy, Smoking, White People, Biological Sciences, Medical and Health Sciences, Genetics & Heredity
Abstract

Epigenetic modifications, including DNA methylation, represent a potential mechanism for environmental impacts on human disease. Maternal smoking in pregnancy remains an important public health problem that impacts child health in a myriad of ways and has potential lifelong consequences. The mechanisms are largely unknown, but epigenetics most likely plays a role. We formed the Pregnancy And Childhood Epigenetics (PACE) consortium and meta-analyzed, across 13 cohorts (n = 6,685), the association between maternal smoking in pregnancy and newborn blood DNA methylation at over 450,000 CpG sites (CpGs) by using the Illumina 450K BeadChip. Over 6,000 CpGs were differentially methylated in relation to maternal smoking at genome-wide statistical significance (false discovery rate, 5%), including 2,965 CpGs corresponding to 2,017 genes not previously related to smoking and methylation in either newborns or adults. Several genes are relevant to diseases that can be caused by maternal smoking (e.g., orofacial clefts and asthma) or adult smoking (e.g., certain cancers). A number of differentially methylated CpGs were associated with gene expression. We observed enrichment in pathways and processes critical to development. In older children (5 cohorts, n = 3,187), 100% of CpGs gave at least nominal levels of significance, far more than expected by chance (p value < 2.2 × 10(-16)). Results were robust to different normalization methods used across studies and cell type adjustment. In this large scale meta-analysis of methylation data, we identified numerous loci involved in response to maternal smoking in pregnancy with persistence into later childhood and provide insights into mechanisms underlying effects of this important exposure.

Published
2016

44. Investigating the relationships between unfavourable habitual sleep and metabolomic traits: evidence from multi-cohort multivariable regression and Mendelian randomization analyses

Author

Bos, Maxime M., Goulding, Neil J., Lee, Matthew A., Hofman, Amy, Bot, Mariska, Pool, René, Vijfhuizen, Lisanne S., Zhang, Xiang, Li, Chihua, Mustafa, Rima, Neville, Matt J., Li-Gao, Ruifang, Trompet, Stella, Beekman, Marian, Biermasz, Nienke R., Boomsma, Dorret I., de Boer, Irene, Christodoulides, Constantinos, Dehghan, Abbas, van Dijk, Ko Willems, Ford, Ian, Ghanbari, Mohsen, Heijmans, Bastiaan T., Ikram, M. Arfan, Jukema, J. Wouter, Mook-Kanamori, Dennis O., Karpe, Fredrik, Luik, Annemarie I., Lumey, L. H., van den Maagdenberg, Arn M. J. M., Mooijaart, Simon P., de Mutsert, Renée, Penninx, Brenda W. J. H., Rensen, Patrick C. N., Richmond, Rebecca C., Rosendaal, Frits R., Sattar, Naveed, Schoevers, Robert A., Slagboom, P. Eline, Terwindt, Gisela M., Thesing, Carisha S., Wade, Kaitlin H., Wijsman, Carolien A., Willemsen, Gonneke, Zwinderman, Aeilko H., van Heemst, Diana, Noordam, Raymond, and Lawlor, Deborah A.

Published
2021
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46. Testing The Validity of Value-Added Measures of Educational Progress With Genetic Data

Author

Morris, Tim T., Davies, Neil M., Dorling, Danny, Richmond, Rebecca C., and Smith, George Davey

Abstract

Value-added measures of educational progress have been used by education researchers and policy-makers to assess the performance of teachers and schools, contributing to performance-related pay and position in school league tables. They are designed to control for all underlying differences between pupils and should therefore provide unbiased measures of school and teacher influence on pupil progress, however, their effectiveness has been questioned. We exploit genetic data from a UK birth cohort to investigate how successfully value-added measures control for genetic differences between pupils. We use raw value-added, contextual value-added (which additionally controls for background characteristics) and teacher-reported value-added measures built from data at ages 11, 14 and 16. Sample sizes for analyses range from 4,600 to 6,518. Our findings demonstrate that genetic differences between pupils explain little variation in raw value-added measures but explain up to 20% of the variation in contextual value-added measures (95% CI = 6.06% to 35.71%). Value-added measures built from teacher-rated ability have a greater proportion of variance explained by genetic differences between pupils, with 36.3% of their cross-sectional variation being statistically accounted for by genetics (95% CI = 22.8% to 49.8%). By contrast, a far greater proportion of variance is explained by genetic differences for raw test scores at each age of at least 47.3% (95% CI: 35.9 to 58.7). These findings provide evidence that value-added measures of educational progress can be influenced by genetic differences between pupils, and therefore may provide a biased measure of school and teacher performance. We include a glossary of genetic terms for educational researchers interested in the use of genetic data in educational research.

Published
2018
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47. Estimating the health impact of nicotine exposure by dissecting the effects of nicotine versus non-nicotine constituents of tobacco smoke: A multivariable Mendelian randomisation study.

Author

Khouja, Jasmine N., Sanderson, Eleanor, Wootton, Robyn E., Taylor, Amy E., Church, Billy A., Richmond, Rebecca C., and Munafò, Marcus R.

Subjects
NICOTINE, TOBACCO smoke, SMOKING, COTININE, CHRONIC obstructive pulmonary disease, GENOME-wide association studies
Abstract

The detrimental health effects of smoking are well-known, but the impact of regular nicotine use without exposure to the other constituents of tobacco is less clear. Given the increasing daily use of alternative nicotine delivery systems, such as e-cigarettes, it is increasingly important to understand and separate the effects of nicotine use from the impact of tobacco smoke exposure. Using a multivariable Mendelian randomisation framework, we explored the direct effects of nicotine compared with the non-nicotine constituents of tobacco smoke on health outcomes (lung cancer, chronic obstructive pulmonary disease [COPD], forced expiratory volume in one second [FEV-1], forced vital capacity [FVC], coronary heart disease [CHD], and heart rate [HR]). We used Genome-Wide Association Study (GWAS) summary statistics from Buchwald and colleagues, the GWAS and Sequencing Consortium of Alcohol and Nicotine, the International Lung Cancer Consortium, and UK Biobank. Increased nicotine metabolism increased the risk of COPD, lung cancer, and lung function in the univariable analysis. However, when accounting for smoking heaviness in the multivariable analysis, we found that increased nicotine metabolite ratio (indicative of decreased nicotine exposure per cigarette smoked) decreases heart rate (b = -0.30, 95% CI -0.50 to -0.10) and lung function (b = -33.33, 95% CI -41.76 to -24.90). There was no clear evidence of an effect on the remaining outcomes. The results suggest that these smoking-related outcomes are not due to nicotine exposure but are caused by the other components of tobacco smoke; however, there are multiple potential sources of bias, and the results should be triangulated using evidence from a range of methodologies. Author summary: Although we know that smoking tobacco negatively impacts health, we know relatively little about whether nicotine plays a role in causing poor health outcomes. When used for short periods of time, nicotine appears to have little impact on health. However, until recently, nicotine has rarely been used for long periods without accompanying exposure to tobacco smoke, so it is hard to disentangle the effects of regular nicotine use from the effects of tobacco smoke exposure. In this study, we aimed to dissect the effects of nicotine versus non-nicotine constituents of tobacco smoke on heart and lung health using multivariable Mendelian randomisation and data from a range of sources (including UK Biobank). We found that nicotine does not appear to be an independent cause of poor lung function, lung cancer, chronic obstructive pulmonary disease, or coronary heart disease, but does increase heart rate. These results support previous evidence which suggests that nicotine on its own does not directly cause poor health outcomes, with the exception of increasing heart rate. [ABSTRACT FROM AUTHOR]

Published
2024
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