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3,794 results on '"Davey-Smith, George"'

1. Principled distillation of UK Biobank phenotype data reveals underlying structure in human variation

Author

Carey, Caitlin E., Shafee, Rebecca, Wedow, Robbee, Elliott, Amanda, Palmer, Duncan S., Compitello, John, Kanai, Masahiro, Abbott, Liam, Schultz, Patrick, Karczewski, Konrad J., Bryant, Samuel C., Cusick, Caroline M., Churchhouse, Claire, Howrigan, Daniel P., King, Daniel, Davey Smith, George, Neale, Benjamin M., Walters, Raymond K., and Robinson, Elise B.

Published
2024
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4. The identification of distinct protective and susceptibility mechanisms for hip osteoarthritis: findings from a genome-wide association study meta-analysis of minimum joint space width and Mendelian randomisation cluster analyses

Author

Faber, Benjamin G, Frysz, Monika, Boer, Cindy G, Evans, Daniel S, Ebsim, Raja, Flynn, Kaitlyn A, Lundberg, Mischa, Southam, Lorraine, Hartley, April, Saunders, Fiona R, Lindner, Claudia, Gregory, Jennifer S, Aspden, Richard M, Lane, Nancy E, Harvey, Nicholas C, Evans, David M, Zeggini, Eleftheria, Davey Smith, George, Cootes, Timothy, Van Meurs, Joyce, Kemp, John P, and Tobias, Jonathan H

Subjects
Arthritis, Clinical Research, Genetics, Aging, Human Genome, 2.1 Biological and endogenous factors, Aetiology, Musculoskeletal, Cartilage, Genome-wide association study, Mendelian randomisation, Osteoarthritis, Clinical Sciences, Public Health and Health Services, Clinical sciences, Epidemiology
Abstract

BackgroundHip minimum joint space width (mJSW) provides a proxy for cartilage thickness. This study aimed to conduct a genome-wide association study (GWAS) of mJSW to (i) identify new genetic determinants of mJSW and (ii) identify which mJSW loci convey hip osteoarthritis (HOA) risk and would therefore be of therapeutic interest.MethodsGWAS meta-analysis of hip mJSW derived from plain X-rays and DXA was performed, stratified by sex and adjusted for age and ancestry principal components. Mendelian randomisation (MR) and cluster analyses were used to examine causal effect of mJSW on HOA.Findings50,745 individuals were included in the meta-analysis. 42 SNPs, which mapped to 39 loci, were identified. Mendelian randomisation (MR) revealed little evidence of a causal effect of mJSW on HOA (ORIVW 0.98 [95% CI 0.82-1.18]). However, MR-Clust analysis suggested the null MR estimates reflected the net effect of two distinct causal mechanisms cancelling each other out, one of which was protective, whereas the other increased HOA susceptibility. For the latter mechanism, all loci were positively associated with height, suggesting mechanisms leading to greater height and mJSW increase the risk of HOA in later life.InterpretationsOne group of mJSW loci reduce HOA risk via increased mJSW, suggesting possible utility as targets for chondroprotective therapies. The second group of mJSW loci increased HOA risk, despite increasing mJSW, but were also positively related to height, suggesting they contribute to HOA risk via a growth-related mechanism.FundingPrimarily funded by the Medical Research Council and Wellcome Trust.

Published
2023

8. Impact of vaccination on the association of COVID-19 with cardiovascular diseases: An OpenSAFELY cohort study

Author

Cezard, Genevieve I., Denholm, Rachel E., Knight, Rochelle, Wei, Yinghui, Teece, Lucy, Toms, Renin, Forbes, Harriet J., Walker, Alex J., Fisher, Louis, Massey, Jon, Hopcroft, Lisa E. M., Horne, Elsie M. F., Taylor, Kurt, Palmer, Tom, Arab, Marwa Al, Cuitun Coronado, Jose Ignacio, Ip, Samantha H. Y., Davy, Simon, Dillingham, Iain, Bacon, Sebastian, Mehrkar, Amir, Morton, Caroline E., Greaves, Felix, Hyams, Catherine, Davey Smith, George, Macleod, John, Chaturvedi, Nishi, Goldacre, Ben, Whiteley, William N., Wood, Angela M., Sterne, Jonathan A. C., and Walker, Venexia

Published
2024
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14. 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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16. Understanding the complex genetic architecture connecting rheumatoid arthritis, osteoporosis and inflammation: discovering causal pathways

Author

Kasher, Melody, Williams, Frances MK, Freidin, Maxim B, Malkin, Ida, Cherny, Stacey S, Benjamin, Emelia, Chasman, Daniel I, Dehghan, Abbas, Ahluwalia, Tarunveer Singh, Meigs, James, Tracy, Russell, Alizadeh, Behrooz Z, Ligthart, Symen, Bis, Josh, Eiriksdottir, Gudny, Pankratz, Nathan, Gross, Myron, Rainer, Alex, Snieder, Harold, Wilson, James G, Psaty, Bruce M, Dupuis, Josee, Prins, Bram, Vaso, Urmo, Stathopoulou, Maria, Franke, Lude, Lehtimaki, Terho, Koenig, Wolfgang, Jamshidi, Yalda, Siest, Sophie, Abbasi, Ali, Uitterlinden, Andre G, Abdollahi, Mohammadreza, Schnabel, Renate, Schick, Ursula M, Nolte, Ilja M, Kraja, Aldi, Hsu, Yi-Hsiang, Tylee, Daniel S, Zwicker, Alyson, Uher, Rudolf, Davey-Smith, George, Morrison, Alanna C, Hicks, Andrew, van Duijn, Cornelia M, Ward-Caviness, Cavin, Boerwinkle, Eric, Rotter, J, Rice, Ken, Lange, Leslie, Perola, Markus, de Geus, Eco, Morris, Andrew P, Makela, Kari Matti, Stacey, David, Eriksson, Johan, Frayling, Tim M, Slagboom, Eline P, and Livshits, Gregory

Subjects
Aging, Autoimmune Disease, Arthritis, Osteoporosis, Human Genome, Heart Disease, Cardiovascular, Rheumatoid Arthritis, Genetics, 2.1 Biological and endogenous factors, Aetiology, Inflammatory and immune system, Arthritis, Rheumatoid, C-Reactive Protein, Genome-Wide Association Study, Humans, Inflammation, Mendelian Randomization Analysis, Polymorphism, Single Nucleotide, CHARGE Inflammation Working Group, Biological Sciences, Medical and Health Sciences, Genetics & Heredity
Abstract

Rheumatoid arthritis (RA) and osteoporosis (OP) are two comorbid complex inflammatory conditions with evidence of shared genetic background and causal relationships. We aimed to clarify the genetic architecture underlying RA and various OP phenotypes while additionally considering an inflammatory component, C-reactive protein (CRP). Genome-wide association study summary statistics were acquired from the GEnetic Factors for OSteoporosis Consortium, Cohorts for Heart and Aging Research Consortium and UK Biobank. Mendelian randomization (MR) was used to detect the presence of causal relationships. Colocalization analysis was performed to determine shared genetic variants between CRP and OP phenotypes. Analysis of pleiotropy between traits owing to shared causal single nucleotide polymorphisms (SNPs) was performed using PL eiotropic A nalysis under CO mposite null hypothesis (PLACO). MR analysis was suggestive of horizontal pleiotropy between RA and OP traits. RA was a significant causal risk factor for CRP (β = 0.027, 95% confidence interval = 0.016-0.038). There was no evidence of CRP→OP causal relationship, but horizontal pleiotropy was apparent. Colocalization established shared genomic regions between CRP and OP, including GCKR and SERPINA1 genes. Pleiotropy arising from shared causal SNPs revealed through the colocalization analysis was all confirmed by PLACO. These genes were found to be involved in the same molecular function 'protein binding' (GO:0005515) associated with RA, OP and CRP. We identified three major components explaining the epidemiological relationship among RA, OP and inflammation: (1) Pleiotropy explains a portion of the shared genetic relationship between RA and OP, albeit polygenically; (2) RA contributes to CRP elevation and (3) CRP, which is influenced by RA, demonstrated pleiotropy with OP.

Published
2022

21. Within-sibship genome-wide association analyses decrease bias in estimates of direct genetic effects

Author

Howe, Laurence J, Nivard, Michel G, Morris, Tim T, Hansen, Ailin F, Rasheed, Humaira, Cho, Yoonsu, Chittoor, Geetha, Ahlskog, Rafael, Lind, Penelope A, Palviainen, Teemu, van der Zee, Matthijs D, Cheesman, Rosa, Mangino, Massimo, Wang, Yunzhang, Li, Shuai, Klaric, Lucija, Ratliff, Scott M, Bielak, Lawrence F, Nygaard, Marianne, Giannelis, Alexandros, Willoughby, Emily A, Reynolds, Chandra A, Balbona, Jared V, Andreassen, Ole A, Ask, Helga, Baras, Aris, Bauer, Christopher R, Boomsma, Dorret I, Campbell, Archie, Campbell, Harry, Chen, Zhengming, Christofidou, Paraskevi, Corfield, Elizabeth, Dahm, Christina C, Dokuru, Deepika R, Evans, Luke M, de Geus, Eco JC, Giddaluru, Sudheer, Gordon, Scott D, Harden, K Paige, Hill, W David, Hughes, Amanda, Kerr, Shona M, Kim, Yongkang, Kweon, Hyeokmoon, Latvala, Antti, Lawlor, Deborah A, Li, Liming, Lin, Kuang, Magnus, Per, Magnusson, Patrik KE, Mallard, Travis T, Martikainen, Pekka, Mills, Melinda C, Njølstad, Pål Rasmus, Overton, John D, Pedersen, Nancy L, Porteous, David J, Reid, Jeffrey, Silventoinen, Karri, Southey, Melissa C, Stoltenberg, Camilla, Tucker-Drob, Elliot M, Wright, Margaret J, Hewitt, John K, Keller, Matthew C, Stallings, Michael C, Lee, James J, Christensen, Kaare, Kardia, Sharon LR, Peyser, Patricia A, Smith, Jennifer A, Wilson, James F, Hopper, John L, Hägg, Sara, Spector, Tim D, Pingault, Jean-Baptiste, Plomin, Robert, Havdahl, Alexandra, Bartels, Meike, Martin, Nicholas G, Oskarsson, Sven, Justice, Anne E, Millwood, Iona Y, Hveem, Kristian, Naess, Øyvind, Willer, Cristen J, Åsvold, Bjørn Olav, Koellinger, Philipp D, Kaprio, Jaakko, Medland, Sarah E, Walters, Robin G, Benjamin, Daniel J, Turley, Patrick, Evans, David M, Davey Smith, George, Hayward, Caroline, Brumpton, Ben, Hemani, Gibran, and Davies, Neil M

Subjects
Human Genome, Genetics, Pediatric, 2.1 Biological and endogenous factors, Aetiology, Mental health, Generic health relevance, Genome-Wide Association Study, Humans, Mendelian Randomization Analysis, Multifactorial Inheritance, Phenotype, Polymorphism, Single Nucleotide, Social Science Genetic Association Consortium, Within Family Consortium, Biological Sciences, Medical and Health Sciences, Developmental Biology
Abstract

Estimates from genome-wide association studies (GWAS) of unrelated individuals capture effects of inherited variation (direct effects), demography (population stratification, assortative mating) and relatives (indirect genetic effects). Family-based GWAS designs can control for demographic and indirect genetic effects, but large-scale family datasets have been lacking. We combined data from 178,086 siblings from 19 cohorts to generate population (between-family) and within-sibship (within-family) GWAS estimates for 25 phenotypes. Within-sibship GWAS estimates were smaller than population estimates for height, educational attainment, age at first birth, number of children, cognitive ability, depressive symptoms and smoking. Some differences were observed in downstream SNP heritability, genetic correlations and Mendelian randomization analyses. For example, the within-sibship genetic correlation between educational attainment and body mass index attenuated towards zero. In contrast, analyses of most molecular phenotypes (for example, low-density lipoprotein-cholesterol) were generally consistent. We also found within-sibship evidence of polygenic adaptation on taller height. Here, we illustrate the importance of family-based GWAS data for phenotypes influenced by demographic and indirect genetic effects.

Published
2022

24. Obesity Partially Mediates the Diabetogenic Effect of Lowering LDL Cholesterol.

Author

Wu, Peitao, Moon, Jee-Young, Daghlas, Iyas, Franco, Giulianini, Porneala, Bianca, Ahmadizar, Fariba, Richardson, Tom, Isaksen, Jonas, Hindy, Georgy, Yao, Jie, Sitlani, Colleen, Raffield, Laura, Yanek, Lisa, Feitosa, Mary, Cuadrat, Rafael, Qi, Qibin, Arfan Ikram, M, Ellervik, Christina, Ericson, Ulrika, Goodarzi, Mark, Brody, Jennifer, Lange, Leslie, Mercader, Josep, Vaidya, Dhananjay, An, Ping, Schulze, Matthias, Masana, Lluis, Ghanbari, Mohsen, Olesen, Morten, Cai, Jianwen, Guo, Xiuqing, Floyd, James, Jäger, Susanne, Province, Michael, Kalyani, Rita, Psaty, Bruce, Orho-Melander, Marju, Ridker, Paul, Kanters, Jørgen, Uitterlinden, Andre, Davey Smith, George, Gill, Dipender, Kaplan, Robert, Kavousi, Maryam, Raghavan, Sridharan, Chasman, Daniel, Rotter, Jerome, Meigs, James, Florez, Jose, Dupuis, Josée, Liu, Ching-Ti, and Merino, Jordi

Subjects
Cholesterol, LDL, Diabetes Mellitus, Type 2, Genome-Wide Association Study, Humans, Mendelian Randomization Analysis, Obesity, Risk Factors
Abstract

OBJECTIVE: LDL cholesterol (LDLc)-lowering drugs modestly increase body weight and type 2 diabetes risk, but the extent to which the diabetogenic effect of lowering LDLc is mediated through increased BMI is unknown. RESEARCH DESIGN AND METHODS: We conducted summary-level univariable and multivariable Mendelian randomization (MR) analyses in 921,908 participants to investigate the effect of lowering LDLc on type 2 diabetes risk and the proportion of this effect mediated through BMI. We used data from 92,532 participants from 14 observational studies to replicate findings in individual-level MR analyses. RESULTS: A 1-SD decrease in genetically predicted LDLc was associated with increased type 2 diabetes odds (odds ratio [OR] 1.12 [95% CI 1.01, 1.24]) and BMI (β = 0.07 SD units [95% CI 0.02, 0.12]) in univariable MR analyses. The multivariable MR analysis showed evidence of an indirect effect of lowering LDLc on type 2 diabetes through BMI (OR 1.04 [95% CI 1.01, 1.08]) with a proportion mediated of 38% of the total effect (P = 0.03). Total and indirect effect estimates were similar across a number of sensitivity analyses. Individual-level MR analyses confirmed the indirect effect of lowering LDLc on type 2 diabetes through BMI with an estimated proportion mediated of 8% (P = 0.04). CONCLUSIONS: These findings suggest that the diabetogenic effect attributed to lowering LDLc is partially mediated through increased BMI. Our results could help advance understanding of adipose tissue and lipids in type 2 diabetes pathophysiology and inform strategies to reduce diabetes risk among individuals taking LDLc-lowering medications.

Published
2022

25. Association between circulating inflammatory markers and adult cancer risk: a Mendelian randomization analysis

Author

Landi, Maria Teresa, Stevens, Victoria, Wang, Ying, Albanes, Demetrios, Caporaso, Neil, Brennan, Paul, Amos, Christopher I., Shete, Sanjay, Hung, Rayjean J., Bickeböller, Heike, Risch, Angela, Houlston, Richard, Lam, Stephen, Tardon, Adonina, Chen, Chu, Bojesen, Stig E., Johansson, Mattias, Wichmann, H-Erich, Christiani, David, Rennert, Gadi, Arnold, Susanne, Field, John K., Le Marchand, Loic, Melander, Olle, Brunnström, Hans, Liu, Geoffrey, Andrew, Angeline, Kiemeney, Lambertus A., Shen, Hongbing, Zienolddiny, Shan, Grankvist, Kjell, Johansson, Mikael, Teare, M. Dawn, Hong, Yun-Chul, Yuan, Jian-Min, Lazarus, Philip, Schabath, Matthew B., Aldrich, Melinda C., Eeles, Rosalind A., Haiman, Christopher A., Kote-Jarai, Zsofia, Schumacher, Fredrick R., Benlloch, Sara, Al Olama, Ali Amin, Muir, Kenneth R., Berndt, Sonja I., Conti, David V., Wiklund, Fredrik, Chanock, Stephen, Tangen, Catherine M., Batra, Jyotsna, Clements, Judith A., Grönberg, Henrik, Pashayan, Nora, Schleutker, Johanna, Albanes, Demetrius, Weinstein, Stephanie J., Wolk, Alicja, West, Catharine M.L., Mucci, Lorelei A., Cancel-Tassin, Géraldine, Koutros, Stella, Sørensen, Karina Dalsgaard, Grindedal, Eli Marie, Neal, David E., Hamdy, Freddie C., Donovan, Jenny L., Travis, Ruth C., Hamilton, Robert J., Ingles, Sue Ann, Rosenstein, Barry S., Lu, Yong-Jie, Giles, Graham G., MacInnis, Robert J., Kibel, Adam S., Vega, Ana, Kogevinas, Manolis, Penney, Kathryn L., Park, Jong Y., Stanfrod, Janet L., Cybulski, Cezary, Nordestgaard, Børge G., Nielsen, Sune F., Brenner, Hermann, Maier, Christiane, Logothetis, Christopher J., John, Esther M., Teixeira, Manuel R., Neuhausen, Susan L., De Ruyck, Kim, Razack, Azad, Newcomb, Lisa F., Lessel, Davor, Kaneva, Radka, Usmani, Nawaid, Claessens, Frank, Townsend, Paul A., Castelao, Jose Esteban, Roobol, Monique J., Menegaux, Florence, Khaw, Kay-Tee, Cannon-Albright, Lisa, Pandha, Hardev, Thibodeau, Stephen N., Hunter, David J., Kraft, Peter, Blot, William J., Riboli, Elio, Yarmolinsky, James, Robinson, Jamie W., Mariosa, Daniela, Karhunen, Ville, Huang, Jian, Dimou, Niki, Murphy, Neil, Burrows, Kimberley, Bouras, Emmanouil, Smith-Byrne, Karl, Lewis, Sarah J., Galesloot, Tessel E., Vermeulen, Sita, Martin, Paul, Hou, Lifang, Newcomb, Polly A., White, Emily, Wu, Anna H., Le Marchand, Loïc, Phipps, Amanda I., Buchanan, Daniel D., Zhao, Sizheng Steven, Gill, Dipender, Chanock, Stephen J., Purdue, Mark P., Davey Smith, George, Herzig, Karl-Heinz, Järvelin, Marjo-Riitta, Amos, Chris I., Dehghan, Abbas, Gunter, Marc J., Tsilidis, Kostas K., and Martin, Richard M.

Published
2024
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29. Genome-wide analysis identifies genetic effects on reproductive success and ongoing natural selection at the FADS locus

Author

Mathieson, Iain, Day, Felix R., Barban, Nicola, Tropf, Felix C., Brazel, David M., Vaez, Ahmad, van Zuydam, Natalie, Bitarello, Bárbara D., Gardner, Eugene J., Akimova, Evelina T., Azad, Ajuna, Bergmann, Sven, Bielak, Lawrence F., Boomsma, Dorret I., Bosak, Kristina, Brumat, Marco, Buring, Julie E., Cesarini, David, Chasman, Daniel I., Chavarro, Jorge E., Cocca, Massimiliano, Concas, Maria Pina, Davey Smith, George, Davies, Gail, Deary, Ian J., Esko, Tõnu, Faul, Jessica D., Franco, Oscar, Ganna, Andrea, Gaskins, Audrey J., Gelemanovic, Andrea, de Geus, Eco J. C., Gieger, Christian, Girotto, Giorgia, Gopinath, Bamini, Grabe, Hans Jörgen, Gunderson, Erica P., Hayward, Caroline, He, Chunyan, van Heemst, Diana, Hill, W. David, Hoffmann, Eva R., Homuth, Georg, Hottenga, Jouke Jan, Huang, Hongyang, Hyppӧnen, Elina, Ikram, M. Arfan, Jansen, Rick, Johannesson, Magnus, Kamali, Zoha, Kardia, Sharon L. R., Kavousi, Maryam, Kifley, Annette, Kiiskinen, Tuomo, Kraft, Peter, Kühnel, Brigitte, Langenberg, Claudia, Liew, Gerald, Lind, Penelope A., Luan, Jian’an, Mägi, Reedik, Magnusson, Patrik K. E., Mahajan, Anubha, Martin, Nicholas G., Mbarek, Hamdi, McCarthy, Mark I., McMahon, George, Medland, Sarah E., Meitinger, Thomas, Metspalu, Andres, Mihailov, Evelin, Milani, Lili, Missmer, Stacey A., Mitchell, Paul, Møllegaard, Stine, Mook-Kanamori, Dennis O., Morgan, Anna, van der Most, Peter J., de Mutsert, Renée, Nauck, Matthias, Nolte, Ilja M., Noordam, Raymond, Penninx, Brenda W. J. H., Peters, Annette, Peyser, Patricia A., Polašek, Ozren, Power, Chris, Pribisalic, Ajka, Redmond, Paul, Rich-Edwards, Janet W., Ridker, Paul M., Rietveld, Cornelius A., Ring, Susan M., Rose, Lynda M., Rueedi, Rico, Shukla, Vallari, Smith, Jennifer A., Stankovic, Stasa, Stefánsson, Kári, Stöckl, Doris, Strauch, Konstantin, Swertz, Morris A., Teumer, Alexander, Thorleifsson, Gudmar, Thorsteinsdottir, Unnur, Thurik, A. Roy, Timpson, Nicholas J., Turman, Constance, Uitterlinden, André G., Waldenberger, Melanie, Wareham, Nicholas J., Weir, David R., Willemsen, Gonneke, Zhao, Jing Hau, Zhao, Wei, Zhao, Yajie, Snieder, Harold, den Hoed, Marcel, Ong, Ken K., Mills, Melinda C., and Perry, John R. B.

Published
2023
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32. Malaria is a cause of iron deficiency in African children

Author

Muriuki, John Muthii, Mentzer, Alexander J, Mitchell, Ruth, Webb, Emily L, Etyang, Anthony O, Kyobutungi, Catherine, Morovat, Alireza, Kimita, Wandia, Ndungu, Francis M, Macharia, Alex W, Ngetsa, Caroline J, Makale, Johnstone, Lule, Swaib A, Musani, Solomon K, Raffield, Laura M, Cutland, Clare L, Sirima, Sodiomon B, Diarra, Amidou, Tiono, Alfred B, Fried, Michal, Gwamaka, Moses, Adu-Afarwuah, Seth, Wirth, James P, Wegmüller, Rita, Madhi, Shabir A, Snow, Robert W, Hill, Adrian VS, Rockett, Kirk A, Sandhu, Manjinder S, Kwiatkowski, Dominic P, Prentice, Andrew M, Byrd, Kendra A, Ndjebayi, Alex, Stewart, Christine P, Engle-Stone, Reina, Green, Tim J, Karakochuk, Crystal D, Suchdev, Parminder S, Bejon, Philip, Duffy, Patrick E, Davey Smith, George, Elliott, Alison M, Williams, Thomas N, and Atkinson, Sarah H

Subjects
Medical Microbiology, Biomedical and Clinical Sciences, Clinical Sciences, Brain Disorders, Pediatric, Infectious Diseases, Malaria, Vector-Borne Diseases, Rare Diseases, Clinical Research, Infection, Good Health and Well Being, Absorption, Physiological, Adolescent, Africa, Child, Child, Preschool, Female, Geography, Hepcidins, Humans, Infant, Iron Deficiencies, Male, Mendelian Randomization Analysis, Sickle Cell Trait, Medical and Health Sciences, Immunology, Biomedical and clinical sciences, Health sciences
Abstract

Malaria and iron deficiency (ID) are common and interrelated public health problems in African children. Observational data suggest that interrupting malaria transmission reduces the prevalence of ID1. To test the hypothesis that malaria might cause ID, we used sickle cell trait (HbAS, rs334 ), a genetic variant that confers specific protection against malaria2, as an instrumental variable in Mendelian randomization analyses. HbAS was associated with a 30% reduction in ID among children living in malaria-endemic countries in Africa (n = 7,453), but not among individuals living in malaria-free areas (n = 3,818). Genetically predicted malaria risk was associated with an odds ratio of 2.65 for ID per unit increase in the log incidence rate of malaria. This suggests that an intervention that halves the risk of malaria episodes would reduce the prevalence of ID in African children by 49%.

Published
2021

34. The identification of distinct protective and susceptibility mechanisms for hip osteoarthritis: findings from a genome-wide association study meta-analysis of minimum joint space width and Mendelian randomisation cluster analyses

Author

Faber, Benjamin G., Frysz, Monika, Boer, Cindy G., Evans, Daniel S., Ebsim, Raja, Flynn, Kaitlyn A., Lundberg, Mischa, Southam, Lorraine, Hartley, April, Saunders, Fiona R., Lindner, Claudia, Gregory, Jennifer S., Aspden, Richard M., Lane, Nancy E., Harvey, Nicholas C., Evans, David M., Zeggini, Eleftheria, Davey Smith, George, Cootes, Timothy, Van Meurs, Joyce, Kemp, John P., and Tobias, Jonathan H.

Published
2023
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37. Immune-mediated genetic pathways resulting in pulmonary function impairment increase lung cancer susceptibility.

Author

Kachuri, Linda, Johansson, Mattias, Rashkin, Sara R, Graff, Rebecca E, Bossé, Yohan, Manem, Venkata, Caporaso, Neil E, Landi, Maria Teresa, Christiani, David C, Vineis, Paolo, Liu, Geoffrey, Scelo, Ghislaine, Zaridze, David, Shete, Sanjay S, Albanes, Demetrius, Aldrich, Melinda C, Tardón, Adonina, Rennert, Gad, Chen, Chu, Goodman, Gary E, Doherty, Jennifer A, Bickeböller, Heike, Field, John K, Davies, Michael P, Dawn Teare, M, Kiemeney, Lambertus A, Bojesen, Stig E, Haugen, Aage, Zienolddiny, Shanbeh, Lam, Stephen, Le Marchand, Loïc, Cheng, Iona, Schabath, Matthew B, Duell, Eric J, Andrew, Angeline S, Manjer, Jonas, Lazarus, Philip, Arnold, Susanne, McKay, James D, Emami, Nima C, Warkentin, Matthew T, Brhane, Yonathan, Obeidat, Ma'en, Martin, Richard M, Relton, Caroline, Davey Smith, George, Haycock, Philip C, Amos, Christopher I, Brennan, Paul, Witte, John S, and Hung, Rayjean J

Subjects
Lung, Humans, Lung Neoplasms, Genetic Predisposition to Disease, Respiratory Function Tests, Vital Capacity, Forced Expiratory Volume, Prospective Studies, Phenotype, Polymorphism, Single Nucleotide, Adult, Aged, Middle Aged, Female, Male, Mendelian Randomization Analysis, Polymorphism, Single Nucleotide
Abstract

Impaired lung function is often caused by cigarette smoking, making it challenging to disentangle its role in lung cancer susceptibility. Investigation of the shared genetic basis of these phenotypes in the UK Biobank and International Lung Cancer Consortium (29,266 cases, 56,450 controls) shows that lung cancer is genetically correlated with reduced forced expiratory volume in one second (FEV1: rg = 0.098, p = 2.3 × 10-8) and the ratio of FEV1 to forced vital capacity (FEV1/FVC: rg = 0.137, p = 2.0 × 10-12). Mendelian randomization analyses demonstrate that reduced FEV1 increases squamous cell carcinoma risk (odds ratio (OR) = 1.51, 95% confidence intervals: 1.21-1.88), while reduced FEV1/FVC increases the risk of adenocarcinoma (OR = 1.17, 1.01-1.35) and lung cancer in never smokers (OR = 1.56, 1.05-2.30). These findings support a causal role of pulmonary impairment in lung cancer etiology. Integrative analyses reveal that pulmonary function instruments, including 73 novel variants, influence lung tissue gene expression and implicate immune-related pathways in mediating the observed effects on lung carcinogenesis.

Published
2020

41. Dairying, diseases and the evolution of lactase persistence in Europe

Author

Evershed, Richard P., Davey Smith, George, Roffet-Salque, Mélanie, Timpson, Adrian, Diekmann, Yoan, Lyon, Matthew S., Cramp, Lucy J. E., Casanova, Emmanuelle, Smyth, Jessica, Whelton, Helen L., Dunne, Julie, Brychova, Veronika, Šoberl, Lucija, Gerbault, Pascale, Gillis, Rosalind E., Heyd, Volker, Johnson, Emily, Kendall, Iain, Manning, Katie, Marciniak, Arkadiusz, Outram, Alan K., Vigne, Jean-Denis, Shennan, Stephen, Bevan, Andrew, Colledge, Sue, Allason-Jones, Lyndsay, Amkreutz, Luc, Anders, Alexandra, Arbogast, Rose-Marie, Bălăşescu, Adrian, Bánffy, Eszter, Barclay, Alistair, Behrens, Anja, Bogucki, Peter, Carrancho Alonso, Ángel, Carretero, José Miguel, Cavanagh, Nigel, Claßen, Erich, Collado Giraldo, Hipolito, Conrad, Matthias, Csengeri, Piroska, Czerniak, Lech, Dębiec, Maciej, Denaire, Anthony, Domboróczki, László, Donald, Christina, Ebert, Julia, Evans, Christopher, Francés-Negro, Marta, Gronenborn, Detlef, Haack, Fabian, Halle, Matthias, Hamon, Caroline, Hülshoff, Roman, Ilett, Michael, Iriarte, Eneko, Jakucs, János, Jeunesse, Christian, Johnson, Melanie, Jones, Andy M., Karul, Necmi, Kiosak, Dmytro, Kotova, Nadezhda, Krause, Rüdiger, Kretschmer, Saskia, Krüger, Marta, Lefranc, Philippe, Lelong, Olivia, Lenneis, Eva, Logvin, Andrey, Lüth, Friedrich, Marton, Tibor, Marley, Jane, Mortimer, Richard, Oosterbeek, Luiz, Oross, Krisztián, Pavúk, Juraj, Pechtl, Joachim, Pétrequin, Pierre, Pollard, Joshua, Pollard, Richard, Powlesland, Dominic, Pyzel, Joanna, Raczky, Pál, Richardson, Andrew, Rowe, Peter, Rowland, Stephen, Rowlandson, Ian, Saile, Thomas, Sebők, Katalin, Schier, Wolfram, Schmalfuß, Germo, Sharapova, Svetlana, Sharp, Helen, Sheridan, Alison, Shevnina, Irina, Sobkowiak-Tabaka, Iwona, Stadler, Peter, Stäuble, Harald, Stobbe, Astrid, Stojanovski, Darko, Tasić, Nenad, van Wijk, Ivo, Vostrovská, Ivana, Vuković, Jasna, Wolfram, Sabine, Zeeb-Lanz, Andrea, and Thomas, Mark G.

Published
2022
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44. Identification of common genetic risk variants for autism spectrum disorder

Author

Grove, Jakob, Ripke, Stephan, Als, Thomas D, Mattheisen, Manuel, Walters, Raymond K, Won, Hyejung, Pallesen, Jonatan, Agerbo, Esben, Andreassen, Ole A, Anney, Richard, Awashti, Swapnil, Belliveau, Rich, Bettella, Francesco, Buxbaum, Joseph D, Bybjerg-Grauholm, Jonas, Bækvad-Hansen, Marie, Cerrato, Felecia, Chambert, Kimberly, Christensen, Jane H, Churchhouse, Claire, Dellenvall, Karin, Demontis, Ditte, De Rubeis, Silvia, Devlin, Bernie, Djurovic, Srdjan, Dumont, Ashley L, Goldstein, Jacqueline I, Hansen, Christine S, Hauberg, Mads Engel, Hollegaard, Mads V, Hope, Sigrun, Howrigan, Daniel P, Huang, Hailiang, Hultman, Christina M, Klei, Lambertus, Maller, Julian, Martin, Joanna, Martin, Alicia R, Moran, Jennifer L, Nyegaard, Mette, Nærland, Terje, Palmer, Duncan S, Palotie, Aarno, Pedersen, Carsten Bøcker, Pedersen, Marianne Giørtz, dPoterba, Timothy, Poulsen, Jesper Buchhave, Pourcain, Beate St, Qvist, Per, Rehnström, Karola, Reichenberg, Abraham, Reichert, Jennifer, Robinson, Elise B, Roeder, Kathryn, Roussos, Panos, Saemundsen, Evald, Sandin, Sven, Satterstrom, F Kyle, Davey Smith, George, Stefansson, Hreinn, Steinberg, Stacy, Stevens, Christine R, Sullivan, Patrick F, Turley, Patrick, Walters, G Bragi, Xu, Xinyi, Stefansson, Kari, Geschwind, Daniel H, Nordentoft, Merete, Hougaard, David M, Werge, Thomas, Mors, Ole, Mortensen, Preben Bo, Neale, Benjamin M, Daly, Mark J, and Børglum, Anders D

Subjects
Intellectual and Developmental Disabilities (IDD), Human Genome, Pediatric, Brain Disorders, Autism, Biotechnology, Genetics, Mental Health, Prevention, 2.3 Psychological, social and economic factors, Aetiology, 2.1 Biological and endogenous factors, Mental health, Adolescent, Autism Spectrum Disorder, Case-Control Studies, Child, Child, Preschool, Denmark, Female, Genetic Predisposition to Disease, Genome-Wide Association Study, Humans, Male, Multifactorial Inheritance, Phenotype, Polymorphism, Single Nucleotide, Risk Factors, Autism Spectrum Disorder Working Group of the Psychiatric Genomics Consortium, BUPGEN, Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium, 23andMe Research Team, Biological Sciences, Medical and Health Sciences, Developmental Biology
Abstract

Autism spectrum disorder (ASD) is a highly heritable and heterogeneous group of neurodevelopmental phenotypes diagnosed in more than 1% of children. Common genetic variants contribute substantially to ASD susceptibility, but to date no individual variants have been robustly associated with ASD. With a marked sample-size increase from a unique Danish population resource, we report a genome-wide association meta-analysis of 18,381 individuals with ASD and 27,969 controls that identified five genome-wide-significant loci. Leveraging GWAS results from three phenotypes with significantly overlapping genetic architectures (schizophrenia, major depression, and educational attainment), we identified seven additional loci shared with other traits at equally strict significance levels. Dissecting the polygenic architecture, we found both quantitative and qualitative polygenic heterogeneity across ASD subtypes. These results highlight biological insights, particularly relating to neuronal function and corticogenesis, and establish that GWAS performed at scale will be much more productive in the near term in ASD.

Published
2019

46. Blood pressure-lowering treatment for prevention of major cardiovascular diseases in people with and without type 2 diabetes: an individual participant-level data meta-analysis

Author

Agodoa, L, Algra, A, Asselbergs, F W, Beckett, N, Berge, E, Black, H, Brouwers, F P J, Brown, M, Bulpitt, C J, Byington, B, Cutler, J, Devereaux, R B, Dwyer, J, Estacio, R, Fagard, R, Fox, K, Fukui, T, Imai, Y, Ishii, M, Julius, S, Kanno, Y, Kjeldsen, S E, Kostis, J, Kuramoto, K, Lanke, J, Lewis, E, Lewis, J, Lievre, M, Lindholm, L H, Lueders, S, MacMahon, S, Mancia, G, Matsuzaki, M, Mehlum, M H, Nissen, S, Ogawa, H, Ogihara, T, Ohkubo, T, Palmer, C, Patel, A, Pfeffer, M, Poulter, N R, Rakugi, H, Reboldi, G, Reid, C, Remuzzi, G, Ruggenenti, P, Saruta, T, Schrader, J, Schrier, R, Sever, P, Sleight, P, Staessen, J A, Suzuki, H, Thijs, L, Ueshima, K, Umemoto, S, van Gilst, W H, Verdecchia, P, Wachtell, K, Whelton, P, Wing, L, Yui, Y, Yusuf, S, Zanchetti, A, Zhang, Z Y, Anderson, C, Baigent, C, Brenner, BM, Collins, R, de Zeeuw, D, Lubsen, J, Malacco, E, Neal, B, Perkovic, V, Pitt, B, Rodgers, A, Rothwell, P, Salimi-Khorshidi, G, Sundström, J, Turnbull, F, Viberti, G, Wang, J, Nazarzadeh, Milad, Bidel, Zeinab, Canoy, Dexter, Copland, Emma, Bennett, Derrick A, Dehghan, Abbas, Davey Smith, George, Holman, Rury R, Woodward, Mark, Gupta, Ajay, Adler, Amanda I, Wamil, Malgorzata, Sattar, Naveed, Cushman, William C, McManus, Richard J, Teo, Koon, Davis, Barry R, Chalmers, John, Pepine, Carl J, and Rahimi, Kazem

Published
2022
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