Search

Your search keyword '"Tyrrell, Jessica"' showing total 566 results
Start Over Author "Tyrrell, Jessica"
566 results on '"Tyrrell, Jessica"'

18. 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

19. 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
Full Text
View/download PDF

20. Investigating the Effect of Motion Capture Suits on the Test–Retest Reliability of Gait Parameters.

Author

Smith, Matt C., Leveridge, Phaedra, Massey, Garry, Tyrrell, Jessica, Hilton, Malcolm, and Williams, Genevieve K. R.

Subjects
MOTION capture (Cinematography), MOTION capture (Human mechanics), INTRACLASS correlation, BIOMECHANICS, ANKLE, TREADMILLS
Abstract

When collecting marker-based motion capture data from clinical populations, speed of collection and comfort for the participant is a priority. This could be achieved by attaching markers to motion capture Velcro suits, as opposed to the skin. This study aimed to ascertain the reliability of sagittal-plane gait parameters estimated using Plug-in Gait (PiG) and Conventional Gait Model 2 (CGM2) marker sets from data collected in Suited and Non-suited (markers placed onto skin) conditions. For ten participants, markers were placed based on PiG and CGM2 models and data captured during a 2-min treadmill walk. Trials were repeated in suited and non-suited conditions. PiG ankle flexion/extension measurements had poor/moderate reliability (Non-suited ICC = 0.531, Suited ICC = 0.435). CGM2 ankle flexion/extension measurements had good/excellent reliability (Non-suited ICC = 0.916, Suited ICC = 0.900). There were significant differences in minimal detectable change (MDC) between conditions at the ankle for PiG (Non-suited MDC = 2.32°, Suited MDC = 18.90°), but not for CGM2 (Non-suited MDC = 0.63°, Suited MDC = 0.95°). When using CGM2, knee (Non-suited ICC = 0.878, Suited ICC = 0.855) and hip (Non-suited ICC = 0.897, Suited ICC = 0.948) showed good/excellent reliability in both conditions. A motion capture suit is not a reliable solution when collecting joint angle data using the PiG model but is reliable enough to consider when using the CGM2 model. [ABSTRACT FROM AUTHOR]

Published
2024
Full Text
View/download PDF

21. Higher maternal adiposity reduces offspring birthweight if associated with a metabolically favourable profile

Author

Thompson, William D., Beaumont, Robin N., Kuang, Alan, Warrington, Nicole M., Ji, Yingjie, Tyrrell, Jessica, Wood, Andrew R., Scholtens, Denise M., Knight, Bridget A., Evans, David M., Lowe, Jr, William L., Santorelli, Gillian, Azad, Rafaq, Mason, Dan, Hattersley, Andrew T., Frayling, Timothy M., Yaghootkar, Hanieh, Borges, Maria Carolina, Lawlor, Deborah A., and Freathy, Rachel M.

Published
2021
Full Text
View/download PDF

24. 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

26. Genome-wide associations for birth weight and correlations with adult disease

Author

Horikoshi, Momoko, Beaumont, Robin N, Day, Felix R, Warrington, Nicole M, Kooijman, Marjolein N, Fernandez-Tajes, Juan, Feenstra, Bjarke, van Zuydam, Natalie R, Gaulton, Kyle J, Grarup, Niels, Bradfield, Jonathan P, Strachan, David P, Li-Gao, Ruifang, Ahluwalia, Tarunveer S, Kreiner, Eskil, Rueedi, Rico, Lyytikäinen, Leo-Pekka, Cousminer, Diana L, Wu, Ying, Thiering, Elisabeth, Wang, Carol A, Have, Christian T, Hottenga, Jouke-Jan, Vilor-Tejedor, Natalia, Joshi, Peter K, Boh, Eileen Tai Hui, Ntalla, Ioanna, Pitkänen, Niina, Mahajan, Anubha, van Leeuwen, Elisabeth M, Joro, Raimo, Lagou, Vasiliki, Nodzenski, Michael, Diver, Louise A, Zondervan, Krina T, Bustamante, Mariona, Marques-Vidal, Pedro, Mercader, Josep M, Bennett, Amanda J, Rahmioglu, Nilufer, Nyholt, Dale R, Ma, Ronald CW, Tam, Claudia HT, Tam, Wing Hung, Ganesh, Santhi K, van Rooij, Frank JA, Jones, Samuel E, Loh, Po-Ru, Ruth, Katherine S, Tuke, Marcus A, Tyrrell, Jessica, Wood, Andrew R, Yaghootkar, Hanieh, Scholtens, Denise M, Paternoster, Lavinia, Prokopenko, Inga, Kovacs, Peter, Atalay, Mustafa, Willems, Sara M, Panoutsopoulou, Kalliope, Wang, Xu, Carstensen, Lisbeth, Geller, Frank, Schraut, Katharina E, Murcia, Mario, van Beijsterveldt, Catharina EM, Willemsen, Gonneke, Appel, Emil VR, Fonvig, Cilius E, Trier, Caecilie, Tiesler, Carla MT, Standl, Marie, Kutalik, Zoltán, Bonàs-Guarch, Sílvia, Hougaard, David M, Sánchez, Friman, Torrents, David, Waage, Johannes, Hollegaard, Mads V, de Haan, Hugoline G, Rosendaal, Frits R, Medina-Gomez, Carolina, Ring, Susan M, Hemani, Gibran, McMahon, George, Robertson, Neil R, Groves, Christopher J, Langenberg, Claudia, Luan, Jian’an, Scott, Robert A, Zhao, Jing Hua, Mentch, Frank D, MacKenzie, Scott M, Reynolds, Rebecca M, Lowe, William L, Tönjes, Anke, Stumvoll, Michael, Lindi, Virpi, Lakka, Timo A, and van Duijn, Cornelia M

Subjects
Nutrition, Perinatal Period - Conditions Originating in Perinatal Period, Human Genome, Genetics, Clinical Research, Preterm, Low Birth Weight and Health of the Newborn, Obesity, Prevention, Pediatric, Infant Mortality, 2.1 Biological and endogenous factors, Aetiology, Adult, Aging, Anthropometry, Birth Weight, Blood Pressure, Chromatin Assembly and Disassembly, Cohort Studies, Coronary Artery Disease, Datasets as Topic, Diabetes Mellitus, Type 2, Female, Fetus, Genetic Loci, Genetic Predisposition to Disease, Genetic Variation, Genome-Wide Association Study, Genomic Imprinting, Genotype, Glucose, Glycogen, Humans, Insulin, Male, Phenotype, Signal Transduction, CHARGE Consortium Hematology Working Group, Early Growth Genetics (EGG) Consortium, General Science & Technology
Abstract

Birth weight (BW) has been shown to be influenced by both fetal and maternal factors and in observational studies is reproducibly associated with future risk of adult metabolic diseases including type 2 diabetes (T2D) and cardiovascular disease. These life-course associations have often been attributed to the impact of an adverse early life environment. Here, we performed a multi-ancestry genome-wide association study (GWAS) meta-analysis of BW in 153,781 individuals, identifying 60 loci where fetal genotype was associated with BW (P

Published
2016

27. Colorectal cancer risk stratification using a polygenic risk score in symptomatic patients presenting to primary care — a UK Biobank retrospective cohort study

Author

Mallabar-Rimmer, Bethan, primary, Merriel, Samuel WD, additional, Webster, Amy P, additional, Wood, Andrew R, additional, Barclay, Matthew, additional, Tyrrell, Jessica, additional, Ruth, Katherine S, additional, Thirlwell, Christina, additional, Oram, Richard, additional, Weedon, Michael N, additional, Bailey, Sarah ER, additional, and Green, Harry D, additional

Published
2023
Full Text
View/download PDF

29. Using human genetics to understand the disease impacts of testosterone in men and women

Author

Ruth, Katherine S, Day, Felix R, Tyrrell, Jessica, Thompson, Deborah J, Wood, Andrew R, Mahajan, Anubha, and Beaumont, Robin N

Subjects
Genetic variation -- Health aspects -- Demographic aspects, Testosterone -- Health aspects, Biological sciences, Health
Abstract

Testosterone supplementation is commonly used for its effects on sexual function, bone health and body composition, yet its effects on disease outcomes are unknown. To better understand this, we identified genetic determinants of testosterone levels and related sex hormone traits in 425,097 UK Biobank study participants. Using 2,571 genome-wide significant associations, we demonstrate that the genetic determinants of testosterone levels are substantially different between sexes and that genetically higher testosterone is harmful for metabolic diseases in women but beneficial in men. For example, a genetically determined 1 s.d. higher testosterone increases the risks of type 2 diabetes (odds ratio (OR) = 1.37 (95% confidence interval (95% CI): 1.22-1.53)) and polycystic ovary syndrome (OR = 1.51 (95% CI: 1.33-1.72)) in women, but reduces type 2 diabetes risk in men (OR = 0.86 (95% CI: 0.76-0.98)). We also show adverse effects of higher testosterone on breast and endometrial cancers in women and prostate cancer in men. Our findings provide insights into the disease impacts of testosterone and highlight the importance of sex-specific genetic analyses. Genetic analysis of data from over 400,000 participants in the UK Biobank Study shows that circulating testosterone levels have sex-specific implications for cardiometabolic diseases and cancer outcomes., Author(s): Katherine S Ruth [sup.1] , Felix R Day [sup.2] , Jessica Tyrrell [sup.1] , Deborah J Thompson [sup.3] , Andrew R Wood [sup.1] , Anubha Mahajan [sup.4] , Robin [...]

Published
2020
Full Text
View/download PDF

30. Exome Chip Meta-analysis Fine Maps Causal Variants and Elucidates the Genetic Architecture of Rare Coding Variants in Smoking and Alcohol Use

Author

Surendran, Praveen, Young, Robin, Barnes, Daniel R., Nielsen, Sune Fallgaard, Rasheed, Asif, Samuel, Maria, Zhao, Wei, Kontto, Jukka, Perola, Markus, Caslake, Muriel, de Craen, Anton J.M., Trompet, Stella, Uria-Nickelsen, Maria, Malarstig, Anders, Reily, Dermot F., Hoek, Maarten, Vogt, Thomas, Jukema, J. Wouter, Sattar, Naveed, Ford, Ian, Packard, Chris J., Alam, Dewan S., Majumder, Abdulla al Shafi, Di Angelantonio, Emanuele, Chowdhury, Rajiv, Amouyel, Philippe, Arveiler, Dominique, Blankenberg, Stefan, Ferrières, Jean, Kee, Frank, Kuulasmaa, Kari, Müller-Nurasyid, Martina, Veronesi, Giovanni, Virtamo, Jarmo, EPIC-CVD Consortium, Frossard, Philippe, Nordestgaard, Børge Grønne, Saleheen, Danish, Danesh, John, Butterworth, Adam S., Howson, Joanna M.M., Erzurumluoglu, A. Mesut, Jackson, Victoria E., Melbourne, Carl A., Varga, Tibor V., Warren, Helen R., Tragante, Vinicius, Tachmazidou, Ioanna, Harris, Sarah E., Evangelou, Evangelos, Marten, Jonathan, Zhang, Weihua, Altmaier, Elisabeth, Luan, Jian’an, Langenberg, Claudia, Scott, Robert A., Yaghootkar, Hanieh, Stirrups, Kathleen, Kanoni, Stavroula, Marouli, Eirini, Karpe, Fredrik, Dominiczak, Anna F., Sever, Peter, Poulter, Neil, Rolandsson, Olov, Baumbach, Clemens, Afaq, Saima, Chambers, John C., Kooner, Jaspal S., Wareham, Nicholas J., Renström, Frida, Hallmans, Göran, Marioni, Riccardo E., Corley, Janie, Starr, John M., Verweij, Niek, de Boer, Rudolf A., van der Meer, Peter, Yavas, Ersin, Vaartjes, Ilonca, Bots, Michiel L., Asselbergs, Folkert W., Grabe, Hans J., Völzke, Henry, Nauck, Matthias, Weiss, Stefan, Pharoah, Paul D.P., Dunning, Alison M., Dennis, Joe G., Thompson, Deborah J., Michailidou, Kyriaki, Easton, Douglas F., Antoniou, Antonis C., Tyrrell, Jessica, Mihailov, Evelin, Samani, Nilesh J., Zhou, Kaixin, Neville, Matthew J., Metspalu, Andres, Palmer, Colin N.A., Hall, Ian P., Strachan, David P., Deary, Ian J., Frayling, Tim M., Hayward, Caroline, van der Harst, Pim, Zeggini, Eleftheria, Understanding Society Scientific Group, Munroe, Patricia B., Jansson, Jan-Håkan, Franks, Paul W., Deloukas, Panos, Caulfield, Mark J., Wain, Louise V., Tobin, Martin D., Brazel, David M., Jiang, Yu, Hughey, Jordan M., Turcot, Valérie, Zhan, Xiaowei, Gong, Jian, Batini, Chiara, Weissenkampen, J. Dylan, Liu, MengZhen, Bertelsen, Sarah, Chou, Yi-Ling, Faul, Jessica D., Haessler, Jeff, Hammerschlag, Anke R., Hsu, Chris, Kapoor, Manav, Lai, Dongbing, Le, Nhung, de Leeuw, Christiaan A., Loukola, Anu, Mangino, Massimo, Pistis, Giorgio, Qaiser, Beenish, Rohde, Rebecca, Shao, Yaming, Stringham, Heather, Wetherill, Leah, Agrawal, Arpana, Bierut, Laura, Chen, Chu, Eaton, Charles B., Goate, Alison, Haiman, Christopher, Heath, Andrew, Iacono, William G., Martin, Nicholas G., Polderman, Tinca J., Reiner, Alex, Rice, John, Schlessinger, David, Scholte, H. Steven, Smith, Jennifer A., Tardif, Jean-Claude, Tindle, Hilary A., van der Leij, Andries R., Boehnke, Michael, Chang-Claude, Jenny, Cucca, Francesco, David, Sean P., Foroud, Tatiana, Kardia, Sharon L.R., Kooperberg, Charles, Laakso, Markku, Lettre, Guillaume, Madden, Pamela, McGue, Matt, North, Kari, Posthuma, Danielle, Spector, Timothy, Stram, Daniel, Weir, David R., Kaprio, Jaakko, Abecasis, Gonçalo R., Liu, Dajiang J., and Vrieze, Scott

Published
2019
Full Text
View/download PDF

31. Methodological approaches, challenges, and opportunities in the application of Mendelian randomisation to lifecourse epidemiology: A systematic literature review

Author

Power, Grace M., primary, Sanderson, Eleanor, additional, Pagoni, Panagiota, additional, Fraser, Abigail, additional, Morris, Tim, additional, Prince, Claire, additional, Frayling, Timothy M., additional, Heron, Jon, additional, Richardson, Tom G., additional, Richmond, Rebecca, additional, Tyrrell, Jessica, additional, Warrington, Nicole, additional, Davey Smith, George, additional, Howe, Laura D., additional, and Tilling, Kate M., additional

Published
2023
Full Text
View/download PDF

36. Hyperglycaemia is a causal risk factor for upper limb pathologies.

Author

Green, Harry D, Burden, Ella, Chen, Ji, Evans, Jonathan, Patel, Kashyap, Wood, Andrew R, Beaumont, Robin N, Tyrrell, Jessica, Frayling, Timothy M, Hattersley, Andrew T, Oram, Richard A, Bowden, Jack, Barroso, Inês, Smith, Christopher, and Weedon, Michael N

Subjects
CARPAL tunnel syndrome, HYPERGLYCEMIA, MUSCULOSKELETAL system diseases, FAT, DIABETES complications, GENETIC techniques
Abstract

Background Diabetes (regardless of type) and obesity are associated with a range of musculoskeletal disorders. The causal mechanisms driving these associations are unknown for many upper limb pathologies. We used genetic techniques to test the causal link between glycemia, obesity and musculoskeletal conditions. Methods In the UK Biobank's unrelated European cohort (N  = 379 708) we performed mendelian randomisation (MR) analyses to test for a causal effect of long-term high glycaemia and adiposity on four musculoskeletal pathologies: frozen shoulder, Dupuytren's disease, carpal tunnel syndrome and trigger finger. We also performed single-gene MR using rare variants in the GCK gene. Results Using MR, we found evidence that long-term high glycaemia has a causal role in the aetiology of upper limb conditions. A 10-mmol/mol increase in genetically predicted haemoglobin A1C (HbA1c) was associated with frozen shoulder: odds ratio (OR) = 1.50 [95% confidence interval (CI), 1.20–1.88], Dupuytren's disease: OR = 1.17 (95% CI, 1.01–1.35), trigger finger: OR = 1.30 (95% CI, 1.09–1.55) and carpal tunnel syndrome: OR = 1.20 (95% CI, 1.09–1.33). Carriers of GCK mutations have increased odds of frozen shoulder: OR = 7.16 (95% CI, 2.93–17.51) and carpal tunnel syndrome: OR = 2.86 (95% CI, 1.50–5.44) but not Dupuytren's disease or trigger finger. We found evidence that an increase in genetically predicted body mass index (BMI) of 5 kg/m2 was associated with carpal tunnel syndrome: OR = 1.13 (95% CI, 1.10–1.16) and associated negatively with Dupuytren's disease: OR = 0.94 (95% CI, 0.90–0.98), but no evidence of association with frozen shoulder or trigger finger. Trigger finger (OR 1.96 (95% CI, 1.42–2.69) P  =   3.6e-05) and carpal tunnel syndrome [OR 1.63 (95% CI, 1.36–1.95) P  =   8.5e-08] are associated with genetically predicted unfavourable adiposity increase of one standard deviation of body fat. Conclusions Our study consistently demonstrates a causal role of long-term high glycaemia in the aetiology of upper limb musculoskeletal conditions. Clinicians treating diabetes patients should be aware of these complications in clinic, specifically those managing the care of GCK mutation carriers. Upper limb musculoskeletal conditions should be considered diabetes complications. [ABSTRACT FROM AUTHOR]

Published
2024
Full Text
View/download PDF

39. The role of body image dissatisfaction in the relationship between body size and disordered eating and self-harm: complimentary Mendelian randomization and mediation analyses

Author

Power, Grace M., Warne, Naomi, Bould, Helen, Casanova, Francesco, Jones, Samuel E., Richardson, Tom G., Tyrrell, Jessica, Davey Smith, George, and Heron, Jon

Abstract

Disordered eating and self-harm commonly co-occur in young people suggesting potential for shared underlying causes. Body image dissatisfaction (BID) has been recognised as a psychological correlate of body size, associated with both disordered eating and self-harm. However, the investigation into etiological pathways early in the lifecourse to provide detail on how body size and BID may foster disordered eating and self-harm remains largely unexplored. Employing data from two large population-based cohorts, the UK Biobank and the Avon Longitudinal Study of Parents And Children (ALSPAC), we conducted bidirectional Mendelian randomization (MR) to determine the causal direction of effect between genetically predicted prepubertal body size and two measures of BID indicating (i) desire to be smaller, and (ii) desire to be larger. We then used multivariable regression followed by counterfactual mediation analyses. Bidirectional MR indicated robust evidence that increased genetically predicted prepubertal body size increased desire to be smaller and decreased desire to be larger. Evidence for the reverse causal direction was negligible. These findings remained very similar across sensitivity analyses. In females and males, multivariable regression analyses demonstrated that being overweight increased the risk of disordered eating (risk ratio (RR), 95% confidence interval (CI): 1.19, 1.01 to 1.40 and 1.98, 1.28 to 3.05, respectively) and self-harm (RR, 95% CI: 1.35, 1.04 to 1.77 and 1.55, 0.86 to 2.81, respectively), while being underweight was protective against disordered eating (RR, 95% CI: 0.57, 0.40 to 0.81 and 0.81, 0.38 to 1.73, respectively). There was weak evidence of an increase in the risk of self-harm among underweight individuals. Mediation analyses indicated that the relationship between being overweight and subsequent disordered eating was largely mediated by the desire to be smaller. Our research carries important public health implications, suggesting distinct risk profiles for self-harm and disordered eating in relation to weight and body image. In addition, a better understanding of genetically predicted prepubertal BID may be valuable in the prevention and treatment of disordered eating and self-harm in adolescence.

Published
2024
Full Text
View/download PDF

40. Using Mendelian Randomisation methods to understand whether diurnal preference is causally related to mental health

Author

O’Loughlin, Jessica, Casanova, Francesco, Jones, Samuel E., Hagenaars, Saskia P., Beaumont, Robin N., Freathy, Rachel M., Watkins, Edward R., Vetter, Céline, Rutter, Martin K., Cain, Sean W., Phillips, Andrew J. K., Windred, Daniel P., Wood, Andrew R., Weedon, Michael N., and Tyrrell, Jessica

Abstract

Late diurnal preference has been linked to poorer mental health outcomes, but the understanding of the causal role of diurnal preference on mental health and wellbeing is currently limited. Late diurnal preference is often associated with circadian misalignment (a mismatch between the timing of the endogenous circadian system and behavioural rhythms), so that evening people live more frequently against their internal clock. This study aims to quantify the causal contribution of diurnal preference on mental health outcomes, including anxiety, depression and general wellbeing and test the hypothesis that more misaligned individuals have poorer mental health and wellbeing using an actigraphy-based measure of circadian misalignment. Multiple Mendelian Randomisation (MR) approaches were used to test causal pathways between diurnal preference and seven well-validated mental health and wellbeing outcomes in up to 451,025 individuals. In addition, observational analyses tested the association between a novel, objective measure of behavioural misalignment (Composite Phase Deviation, CPD) and seven mental health and wellbeing outcomes. Using genetic instruments identified in the largest GWAS for diurnal preference, we provide robust evidence that early diurnal preference is protective for depression and improves wellbeing. For example, using one-sample MR, a twofold higher genetic liability of morningness was associated with lower odds of depressive symptoms (OR: 0.92, 95% CI: 0.88, 0.97). It is possible that behavioural factors including circadian misalignment may contribute in the chronotype depression relationship, but further work is needed to confirm these findings.

Published
2024
Full Text
View/download PDF

41. Genome-wide association analysis of self-reported daytime sleepiness identifies 42 loci that suggest biological subtypes

Author

Wang, Heming, Lane, Jacqueline M., Jones, Samuel E., Dashti, Hassan S., Ollila, Hanna M., Wood, Andrew R., van Hees, Vincent T., Brumpton, Ben, Winsvold, Bendik S., Kantojärvi, Katri, Palviainen, Teemu, Cade, Brian E., Sofer, Tamar, Song, Yanwei, Patel, Krunal, Anderson, Simon G., Bechtold, David A., Bowden, Jack, Emsley, Richard, Kyle, Simon D., Little, Max A., Loudon, Andrew S., Scheer, Frank A. J. L., Purcell, Shaun M., Richmond, Rebecca C., Spiegelhalder, Kai, Tyrrell, Jessica, Zhu, Xiaofeng, Hublin, Christer, Kaprio, Jaakko A., Kristiansson, Kati, Sulkava, Sonja, Paunio, Tiina, Hveem, Kristian, Nielsen, Jonas B., Willer, Cristen J., Zwart, John-Anker, Strand, Linn B., Frayling, Timothy M., Ray, David, Lawlor, Deborah A., Rutter, Martin K., Weedon, Michael N., Redline, Susan, and Saxena, Richa

Published
2019
Full Text
View/download PDF

42. Genetic studies of accelerometer-based sleep measures yield new insights into human sleep behaviour

Author

Jones, Samuel E., van Hees, Vincent T., Mazzotti, Diego R., Marques-Vidal, Pedro, Sabia, Séverine, van der Spek, Ashley, Dashti, Hassan S., Engmann, Jorgen, Kocevska, Desana, Tyrrell, Jessica, Beaumont, Robin N., Hillsdon, Melvyn, Ruth, Katherine S., Tuke, Marcus A., Yaghootkar, Hanieh, Sharp, Seth A., Ji, Yingjie, Harrison, Jamie W., Freathy, Rachel M., Murray, Anna, Luik, Annemarie I., Amin, Najaf, Lane, Jacqueline M., Saxena, Richa, Rutter, Martin K., Tiemeier, Henning, Kutalik, Zoltán, Kumari, Meena, Frayling, Timothy M., Weedon, Michael N., Gehrman, Philip R., and Wood, Andrew R.

Published
2019
Full Text
View/download PDF

43. Genome-wide association study identifies genetic loci for self-reported habitual sleep duration supported by accelerometer-derived estimates

Author

Dashti, Hassan S., Jones, Samuel E., Wood, Andrew R., Lane, Jacqueline M., van Hees, Vincent T., Wang, Heming, Rhodes, Jessica A., Song, Yanwei, Patel, Krunal, Anderson, Simon G., Beaumont, Robin N., Bechtold, David A., Bowden, Jack, Cade, Brian E., Garaulet, Marta, Kyle, Simon D., Little, Max A., Loudon, Andrew S., Luik, Annemarie I., Scheer, Frank A. J. L., Spiegelhalder, Kai, Tyrrell, Jessica, Gottlieb, Daniel J., Tiemeier, Henning, Ray, David W., Purcell, Shaun M., Frayling, Timothy M., Redline, Susan, Lawlor, Deborah A., Rutter, Martin K., Weedon, Michael N., and Saxena, Richa

Published
2019
Full Text
View/download PDF

44. Identification and analysis of individuals who deviate from their genetically-predicted phenotype.

Author

Hawkes, Gareth, Yengo, Loic, Vedantam, Sailaja, Marouli, Eirini, Beaumont, Robin N., Tyrrell, Jessica, Weedon, Michael N., Hirschhorn, Joel, Frayling, Timothy M., and Wood, Andrew R.

Subjects
HUMAN phenotype, LDL cholesterol, GENOME-wide association studies, CARDIOVASCULAR diseases risk factors, GENETIC variation, PHENOTYPES
Abstract

Findings from genome-wide association studies have facilitated the generation of genetic predictors for many common human phenotypes. Stratifying individuals misaligned to a genetic predictor based on common variants may be important for follow-up studies that aim to identify alternative causal factors. Using genome-wide imputed genetic data, we aimed to classify 158,951 unrelated individuals from the UK Biobank as either concordant or deviating from two well-measured phenotypes. We first applied our methods to standing height: our primary analysis classified 244 individuals (0.15%) as misaligned to their genetically predicted height. We show that these individuals are enriched for self-reporting being shorter or taller than average at age 10, diagnosed congenital malformations, and rare loss-of-function variants in genes previously catalogued as causal for growth disorders. Secondly, we apply our methods to LDL cholesterol. We classified 156 (0.12%) individuals as misaligned to their genetically predicted LDL cholesterol and show that these individuals were enriched for both clinically actionable cardiovascular risk factors and rare genetic variants in genes previously shown to be involved in metabolic processes. Individuals whose LDL-C was higher than expected based on the genetic predictor were also at higher risk of developing coronary artery disease and type-two diabetes, even after adjustment for measured LDL-C, BMI and age, suggesting upward deviation from genetically predicted LDL-C is indicative of generally poor health. Our results remained broadly consistent when performing sensitivity analysis based on a variety of parametric and non-parametric methods to define individuals deviating from polygenic expectation. Our analyses demonstrate the potential importance of quantitatively identifying individuals for further follow-up based on deviation from genetic predictions. Author summary: Human genetics is becoming increasingly useful to help predict human traits across a population owing to findings from large-scale genetic association studies and advances in the power of genetic predictors. This provides an opportunity to potentially identify individuals that deviate from genetic predictions for a common phenotype under investigation. For example, an individual may be genetically predicted to be tall, but be shorter than expected. It is potentially important to identify individuals who deviate from genetic predictions as this can facilitate further follow-up to assess likely causes. Using 158,951 unrelated individuals from the UK Biobank, with height and LDL cholesterol, as exemplar traits, we demonstrate that approximately 0.15% & 0.12% of individuals deviate from their genetically predicted phenotypes respectively. We observed these individuals to be enriched for a range of rare clinical diagnoses, as well as rare genetic factors that may be causal. Our analyses also demonstrate several methods for detecting individuals who deviate from genetic predictions that can be applied to a range of continuous human phenotypes. [ABSTRACT FROM AUTHOR]

Published
2023
Full Text
View/download PDF

46. Genetic evidence that high BMI in childhood has a protective effect on intermediate diabetes traits, including measures of insulin sensitivity and secretion

Author

Hawkes, Gareth, primary, Beaumont, Robin N, additional, Tyrrell, Jessica, additional, Power, Grace M, additional, Wood, Andrew, additional, Laakso, Markku, additional, Silva, Lilian Fernandes, additional, Boehnke, Michael, additional, Yin, Xianyong, additional, Richardson, Tom G, additional, Davey Smith, George, additional, and Frayling, Timothy M, additional

Published
2023
Full Text
View/download PDF

50. Additional file 3 of Mendelian randomisation study of body composition and depression in people of East Asian ancestry highlights potential setting-specific causality

Author

O’Loughlin, Jessica, Casanova, Francesco, Fairhurst-Hunter, Zammy, Hughes, Amanda, Bowden, Jack, Watkins, Edward R., Freathy, Rachel M., Millwood, Iona Y., Lin, Kuang, Chen, Zhengming, Li, Liming, Lv, Jun, Walters, Robin G., Howe, Laura D., Kuchenbaecker, Karoline, and Tyrrell, Jessica

Abstract

Additional file 3: Fig. S1. Observational and genetic associationsbetween WHR and depressive symptoms. Fig. S2. The genetic 1-sample MR estimatesof BMI to depressive symptoms stratified by sex and region. Fig. S3. Thegenetic 1-sample MR estimates of BMI to major depression stratified by sex andregion. Figs. S4-S8. Scatter plots of SNP-depression outcome vs. SNP-BMI2-sample MR analyses. Figs. S9-S13. Scatter plots of SNP-depression outcome vs.SNP-WHR 2-sample MR analyses.

Published
2023
Full Text
View/download PDF

Catalog

Books, media, physical & digital resources
See catalog results