Search

Your search keyword '"Beaumont, Robin"' showing total 524 results
Start Over Author "Beaumont, Robin"
524 results on '"Beaumont, Robin"'

151. Development and Standardization of an Improved Type 1 Diabetes Genetic Risk Score for Use in Newborn Screening and Incident Diagnosis

Author

Sharp, Seth A., primary, Rich, Stephen S., additional, Wood, Andrew R., additional, Jones, Samuel E., additional, Beaumont, Robin N., additional, Harrison, James W., additional, Schneider, Darius A., additional, Locke, Jonathan M., additional, Tyrrell, Jess, additional, Weedon, Michael N., additional, Hagopian, William A., additional, and Oram, Richard A., additional

Published
2019
Full Text
View/download PDF

152. 2DOES HIGH BMI IN THE ABSENCE OF METABOLIC CONSEQUENCES CAUSE DEPRESSION?

Author

Tyrrell, Jess, primary, Mulugeta, Anwar, additional, Wood, Andrew, additional, Zhou, Ang, additional, Beaumont, Robin, additional, Tuke, Marcus, additional, Jones, Samuel, additional, Ruth, Katherine, additional, Yaghootkar, Hanieh, additional, Lewis, Cathryn, additional, Frayling, Tim, additional, and Hypponen, Elina, additional

Published
2019
Full Text
View/download PDF

153. Effects of body mass index on relationship status, social contact and socio-economic position: Mendelian randomization and within-sibling study in UK Biobank.

Author

Howe, Laura D, Kanayalal, Roshni, Harrison, Sean, Beaumont, Robin N, Davies, Alisha R, Frayling, Timothy M, Davies, Neil M, Hughes, Amanda, Jones, Samuel E, Sassi, Franco, Wood, Andrew R, and Tyrrell, Jessica

Subjects
BODY mass index, SOCIAL interaction, RELATIONSHIP status, SOCIAL participation, PARASOCIAL relationships, WAIST circumference, UNMARRIED couples, RESEARCH, TISSUE banks, RESEARCH methodology, MEDICAL cooperation, EVALUATION research, COMPARATIVE studies
Abstract

Background: We assessed whether body mass index (BMI) affects social and socio-economic outcomes.Methods: We used Mendelian randomization (MR), non-linear MR and non-genetic and MR within-sibling analyses, to estimate relationships of BMI with six socio-economic and four social outcomes in 378 244 people of European ancestry in UK Biobank.Results: In MR of minimally related individuals, higher BMI was related to higher deprivation, lower income, fewer years of education, lower odds of degree-level education and skilled employment. Non-linear MR suggested both low (bottom decile, <22 kg/m2) and high (top seven deciles, >24.6 kg/m2) BMI, increased deprivation and reduced income. Non-genetic within-sibling analysis supported an effect of BMI on socio-economic position (SEP); precision in within-sibling MR was too low to draw inference about effects of BMI on SEP. There was some evidence of pleiotropy, with MR Egger suggesting limited effects of BMI on deprivation, although precision of these estimates is also low. Non-linear MR suggested that low BMI (bottom three deciles, <23.5 kg/m2) reduces the odds of cohabiting with a partner or spouse in men, whereas high BMI (top two deciles, >30.7 kg/m2) reduces the odds of cohabitation in women. Both non-genetic and MR within-sibling analyses supported this sex-specific effect of BMI on cohabitation. In men only, higher BMI was related to lower participation in leisure and social activities. There was little evidence that BMI affects visits from friends and family or having someone to confide in.Conclusions: BMI may affect social and socio-economic outcomes, with both high and low BMI being detrimental for SEP, although larger within-family MR studies may help to test the robustness of MR results in unrelated individuals. Triangulation of evidence across MR and within-family analyses supports evidence of a sex-specific effect of BMI on cohabitation. [ABSTRACT FROM AUTHOR]

Published
2020
Full Text
View/download PDF

154. Using genetics to understand the causal influence of higher BMI on depression

Author

Tyrrell, Jessica, primary, Mulugeta, Anwar, additional, Wood, Andrew R, additional, Zhou, Ang, additional, Beaumont, Robin N, additional, Tuke, Marcus A, additional, Jones, Samuel E, additional, Ruth, Katherine S, additional, Yaghootkar, Hanieh, additional, Sharp, Seth, additional, Thompson, William D, additional, Ji, Yingjie, additional, Harrison, Jamie, additional, Freathy, Rachel M, additional, Murray, Anna, additional, Weedon, Michael N, additional, Lewis, Cathryn, additional, Frayling, Timothy M, additional, and Hyppönen, Elina, additional

Published
2018
Full Text
View/download PDF

155. Genome-Wide and Abdominal MRI Data Provide Evidence That a Genetically Determined Favorable Adiposity Phenotype Is Characterized by Lower Ectopic Liver Fat and Lower Risk of Type 2 Diabetes, Heart Disease, and Hypertension

Author

Ji, Yingjie, primary, Yiorkas, Andrianos M., additional, Frau, Francesca, additional, Mook-Kanamori, Dennis, additional, Staiger, Harald, additional, Thomas, E. Louise, additional, Atabaki-Pasdar, Naeimeh, additional, Campbell, Archie, additional, Tyrrell, Jessica, additional, Jones, Samuel E., additional, Beaumont, Robin N., additional, Wood, Andrew R., additional, Tuke, Marcus A., additional, Ruth, Katherine S., additional, Mahajan, Anubha, additional, Murray, Anna, additional, Freathy, Rachel M., additional, Weedon, Michael N., additional, Hattersley, Andrew T., additional, Hayward, Caroline, additional, Machann, Jürgen, additional, Häring, Hans-Ulrich, additional, Franks, Paul, additional, de Mutsert, Renée, additional, Pearson, Ewan, additional, Stefan, Norbert, additional, Frayling, Timothy M., additional, Allebrandt, Karla V., additional, Bell, Jimmy D., additional, Blakemore, Alexandra I., additional, and Yaghootkar, Hanieh, additional

Published
2018
Full Text
View/download PDF

156. Genetic studies of accelerometer-based sleep measures in 85,670 individuals yield new insights into human sleep behaviour

Author

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

Published
2018
Full Text
View/download PDF

157. GWAS in 446,118 European adults identifies 78 genetic loci for self-reported habitual sleep duration supported by accelerometer-derived estimates

Author

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

Published
2018
Full Text
View/download PDF

158. Meta-analysis of genome-wide association studies for body fat distribution in 694,649 individuals of European ancestry

Author

Pulit, Sara L., primary, Stoneman, Charli, additional, Morris, Andrew P., additional, Wood, Andrew R., additional, Glastonbury, Craig A., additional, Tyrrell, Jessica, additional, Yengo, Loïc, additional, Ferreira, Teresa, additional, Marouli, Eirini, additional, Ji, Yingjie, additional, Yang, Jian, additional, Jones, Samuel, additional, Beaumont, Robin, additional, Croteau-Chonka, Damien C., additional, Winkler, Thomas W., additional, Consortium, Giant, additional, Hattersley, Andrew. T., additional, Loos, Ruth J. F., additional, Hirschhorn, Joel N., additional, Visscher, Peter M., additional, Frayling, Timothy M., additional, Yaghootkar, Hanieh, additional, and Lindgren, Cecilia M., additional

Published
2018
Full Text
View/download PDF

159. GWAS identifies novel risk locus for erectile dysfunction and implicates hypothalamic neurobiology and diabetes in etiology

Author

Bovijn, Jonas, primary, Jackson, Leigh, additional, Censin, Jenny, additional, Chen, Chia-Yen, additional, Laisk-Podar, Triin, additional, Laber, Samantha, additional, Ferreira, Teresa, additional, Glastonbury, Craig, additional, Smoller, Jordan, additional, Harrison, Jamie W, additional, Ruth, Katherine S, additional, Beaumont, Robin N, additional, Jones, Samuel E, additional, Tyrrell, Jessica, additional, Wood, Andrew R, additional, Weedon, Michael N, additional, Mägi, Reedik, additional, Neale, Benjamin, additional, Lindgren, Cecilia M, additional, Murray, Anna, additional, and Holmes, Michael V, additional

Published
2018
Full Text
View/download PDF

160. Genome-wide Study of Atrial Fibrillation Identifies Seven Risk Loci and Highlights Biological Pathways and Regulatory Elements Involved in Cardiac Development

Author

Nielsen, Jonas B., Fritsche, Lars G., Zhou, Wei, Teslovich, Tanya M., Holmen, Oddgeir L., Gustafsson, Stefan, Gabrielsen, Maiken E., Schmidt, Ellen M., Beaumont, Robin, Wolford, Brooke N., Lin, Maoxuan, Brummett, Chad M., Preuss, Michael H., Refsgaard, Lena, Bottinger, Erwin P., Graham, Sarah E., Surakka, Ida, Chu, Yunhan, Skogholt, Anne Heidi, Dalen, Havard, Boyle, Alan P., Oral, Hakan, Herron, Todd J., Kitzman, Jacob, Jalife, Jose, Svendsen, Jesper H., Olesen, Morten S., Njolstad, Inger, Lochen, Maja-Lisa, Baras, Aris, Gottesman, Omri, Marcketta, Anthony, O'Dushlaine, Colm, Ritchie, Marylyn D., Wilsgaard, Tom, Loos, Ruth J. F., Frayling, Timothy M., Boehnke, Michael, Ingelsson, Erik, Carey, David J., Dewey, Frederick E., Kang, Hyun M., Abecasis, Goncalo R., Hveem, Kristian, Willer, Cristen J., Nielsen, Jonas B., Fritsche, Lars G., Zhou, Wei, Teslovich, Tanya M., Holmen, Oddgeir L., Gustafsson, Stefan, Gabrielsen, Maiken E., Schmidt, Ellen M., Beaumont, Robin, Wolford, Brooke N., Lin, Maoxuan, Brummett, Chad M., Preuss, Michael H., Refsgaard, Lena, Bottinger, Erwin P., Graham, Sarah E., Surakka, Ida, Chu, Yunhan, Skogholt, Anne Heidi, Dalen, Havard, Boyle, Alan P., Oral, Hakan, Herron, Todd J., Kitzman, Jacob, Jalife, Jose, Svendsen, Jesper H., Olesen, Morten S., Njolstad, Inger, Lochen, Maja-Lisa, Baras, Aris, Gottesman, Omri, Marcketta, Anthony, O'Dushlaine, Colm, Ritchie, Marylyn D., Wilsgaard, Tom, Loos, Ruth J. F., Frayling, Timothy M., Boehnke, Michael, Ingelsson, Erik, Carey, David J., Dewey, Frederick E., Kang, Hyun M., Abecasis, Goncalo R., Hveem, Kristian, and Willer, Cristen J.

Abstract

Atrial fibrillation (AF) is a common cardiac arrhythmia and a major risk factor for stroke, heart failure, and premature death. The pathogenesis of AF remains poorly understood, which contributes to the current lack of highly effective treatments. To understand the genetic variation and biology underlying AF, we undertook a genome-wide association study (GWAS) of 6,337 AF individuals and 61,607 AF-free individuals from Norway, including replication in an additional 30,679 AF individuals and 278,895 AF-free individuals. Through genotyping and dense imputation mapping from whole-genome sequencing, we tested almost nine million genetic variants across the genome and identified seven risk loci, including two novel loci. One novel locus (lead single-nucleotide variant [SNV] rs12614435; p = 6.76 × 10−18) comprised intronic and several highly correlated missense variants situated in the I-, A-, and M-bands of titin, which is the largest protein in humans and responsible for the passive elasticity of heart and skeletal muscle. The other novel locus (lead SNV rs56202902; p = 1.54 × 10−11) covered a large, gene-dense chromosome 1 region that has previously been linked to cardiac conduction. Pathway and functional enrichment analyses suggested that many AF-associated genetic variants act through a mechanism of impaired muscle cell differentiation and tissue formation during fetal heart development.

Published
2018
Full Text
View/download PDF

161. Notes

Author

Parshall, Peter, Landau, David, Massing, Jean Michel, Fuhring, Peter, de Beaumont, Robin, and Lyles, Anne

Published
1986

162. 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 Ching Wan, Tam, Claudia Ha Ting, Tam, Wing Hung, CHARGE Consortium Hematology Working Group, 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, Bonas-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, Early Growth Genetics (EGG) Consortium, Lowe, William L, Tönjes, Anke, Stumvoll, Michael, and Lindi, Virpi

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

163. Genome-Wide Association Analyses in 128,266 Individuals Identifies New Morningness and Sleep Duration Loci

Author

Jones, Samuel E., Tyrrell, Jessica, Wood, Andrew R., Beaumont, Robin N., Ruth, Katherine S., Tuke, Marcus A., Yaghootkar, Hanieh, Hu, Youna, Teder-Laving, Maris, Hayward, Caroline, Roenneberg, Till, Wilson, James F., Del Greco, Fabiola, Hicks, Andrew A., Shin, Chol, Yun, Chang-Ho, Lee, Seung Ku, Metspalu, Andres, Byrne, Enda M., Gehrman, Philip R., Tiemeier, Henning, Allebrandt, Karla V., Freathy, Rachel M., Murray, Anna, Hinds, David A., Frayling, Timothy M., Weedon, Michael N., Epidemiology, Psychiatry, and Shi, Jianxin

Subjects
Male, lcsh:QH426-470, Physiology, Endocrine Disorders, Protein Serine-Threonine Kinases, Research and Analysis Methods, White People, Body Mass Index, PAX8 Transcription Factor, Endocrinology, Mathematical and Statistical Techniques, SDG 3 - Good Health and Well-being, Mental Health and Psychiatry, Medicine and Health Sciences, Genetics, Genome-Wide Association Studies, Diabetes Mellitus, Humans, Obesity, Statistical Methods, Biology and Life Sciences, Computational Biology, Human Genetics, Genomics, Mendelian Randomization Analysis, Genome Analysis, Type 2 Diabetes, Circadian Rhythm, Circadian Rhythms, lcsh:Genetics, Diabetes Mellitus, Type 2, Genetic Loci, Metabolic Disorders, Physical Sciences, Genetics of Disease, Schizophrenia, Female, Physiological Processes, Sleep, Chronobiology, Mathematics, Statistics (Mathematics), Research Article, Meta-Analysis, Genome-Wide Association Study
Abstract

Disrupted circadian rhythms and reduced sleep duration are associated with several human diseases, particularly obesity and type 2 diabetes, but until recently, little was known about the genetic factors influencing these heritable traits. We performed genome-wide association studies of self-reported chronotype (morning/evening person) and self-reported sleep duration in 128,266 white British individuals from the UK Biobank study. Sixteen variants were associated with chronotype (P, Author Summary Numerous studies have identified links between too little or too much sleep and circadian misalignment with metabolic disorders such as obesity and type 2 diabetes. However, cause-and-effect is not easily determined, because of multiple confounding factors affecting both sleep patterns and disease risk. Using the first release of the UK Biobank study, which combines detailed measurements and questionnaire data with genetic data, we investigate the genetics of two self-report sleep measures, chronotype and average sleep duration, in 128,266 white British individuals. We replicate previous genetic associations and identify seven and two novel genetic variants influencing chronotype and sleep duration, respectively. Associated variants are located near genes implicated in circadian rhythm regulation (RGS16, PER2), near a serotonin receptor gene (HTR6) and another gene (INADL) encoding a protein thought to be important in photosensitive retinal cells, cells known to communicate with the brain’s primary circadian pacemaker. Using the genetic risk factors, we estimate the unconfounded causal associations of BMI and type 2 diabetes on sleep patterns (and vice versa) through Mendelian Randomisation. However, we find no evidence for causal associations in either direction. The full UK Biobank release of 500,000 individuals will boost our power to detect causal associations.

Published
2016
Full Text
View/download PDF

164. Telomere length and risk of idiopathic pulmonary fibrosis and chronic obstructive pulmonary disease: a mendelian randomisation study

Author

Duckworth, Anna, Gibbons, Michael A, Allen, Richard J, Almond, Howard, Beaumont, Robin N, Wood, Andrew R, Lunnon, Katie, Lindsay, Mark A, Wain, Louise V, Tyrrell, Jess, and Scotton, Chris J

Abstract

Idiopathic pulmonary fibrosis (IPF) is a fatal lung disease accounting for 1% of UK deaths. In the familial form of pulmonary fibrosis, causal genes have been identified in about 30% of cases, and a majority of these causal genes are associated with telomere maintenance. Prematurely shortened leukocyte telomere length is associated with IPF and chronic obstructive pulmonary disease (COPD), a disease with similar demographics and shared risk factors. Using mendelian randomisation, we investigated evidence supporting a causal role for short telomeres in IPF and COPD.

Published
2021
Full Text
View/download PDF

166. Evidence of a common causal relationship between body mass index and inflammatory skin disease: a Mendelian Randomization study

Author

Budu-Aggrey, Ashley, primary, Brumpton, Ben, additional, Tyrrell, Jess, additional, Watkins, Sarah, additional, Modalsli, Ellen H, additional, Celis-Morales, Carlos, additional, Ferguson, Lyn D, additional, Vie, Gunnhild Åberge, additional, Palmer, Tom, additional, Fritsche, Lars G, additional, Løset, Mari, additional, Nielsen, Jonas Bille, additional, Zhou, Wei, additional, Tsoi, Lam C, additional, Wood, Andrew R, additional, Jones, Samuel E, additional, Beaumont, Robin, additional, Saunes, Marit, additional, Romundstad, Pål Richard, additional, Siebert, Stefan, additional, McInnes, Iain B, additional, Elder, James T, additional, Smith, George Davey, additional, Frayling, Timothy M, additional, Åsvold, Bjørn Olav, additional, Brown, Sara J, additional, Sattar, Naveed, additional, and Paternoster, Lavinia, additional

Published
2018
Full Text
View/download PDF

167. Genome-wide Study of Atrial Fibrillation Identifies Seven Risk Loci and Highlights Biological Pathways and Regulatory Elements Involved in Cardiac Development

Author

Nielsen, Jonas B., primary, Fritsche, Lars G., additional, Zhou, Wei, additional, Teslovich, Tanya M., additional, Holmen, Oddgeir L., additional, Gustafsson, Stefan, additional, Gabrielsen, Maiken E., additional, Schmidt, Ellen M., additional, Beaumont, Robin, additional, Wolford, Brooke N., additional, Lin, Maoxuan, additional, Brummett, Chad M., additional, Preuss, Michael H., additional, Refsgaard, Lena, additional, Bottinger, Erwin P., additional, Graham, Sarah E., additional, Surakka, Ida, additional, Chu, Yunhan, additional, Skogholt, Anne Heidi, additional, Dalen, Håvard, additional, Boyle, Alan P., additional, Oral, Hakan, additional, Herron, Todd J., additional, Kitzman, Jacob, additional, Jalife, José, additional, Svendsen, Jesper H., additional, Olesen, Morten S., additional, Njølstad, Inger, additional, Løchen, Maja-Lisa, additional, Baras, Aris, additional, Gottesman, Omri, additional, Marcketta, Anthony, additional, O’Dushlaine, Colm, additional, Ritchie, Marylyn D., additional, Wilsgaard, Tom, additional, Loos, Ruth J.F., additional, Frayling, Timothy M., additional, Boehnke, Michael, additional, Ingelsson, Erik, additional, Carey, David J., additional, Dewey, Frederick E., additional, Kang, Hyun M., additional, Abecasis, Gonçalo R., additional, Hveem, Kristian, additional, and Willer, Cristen J., additional

Published
2018
Full Text
View/download PDF

168. A common allele in FGF21 associated with preference for sugar consumption lowers body fat in the lower body and increases blood pressure

Author

Frayling, Timothy M., primary, Beaumont, Robin N., additional, Jones, Samuel E., additional, Yaghootkar, Hanieh, additional, Tuke, Marcus A., additional, Ruth, Katherine S., additional, Casanova, Francesco, additional, West, Ben, additional, Locke, Jonathan, additional, Sharp, Seth, additional, Ji, Yingjie, additional, Thompson, William, additional, Harrison, Jamie, additional, Lindgren, Cecilia M., additional, Grarup, Niels, additional, Murray, Anna, additional, Freathy, Rachel M., additional, Weedon, Michael N., additional, Tyrrell, Jessica, additional, and Wood, Andrew R., additional

Published
2017
Full Text
View/download PDF

169. CNV-association meta-analysis in 191,161 European adults reveals new loci associated with anthropometric traits

Author

Macé, Aurélien, primary, Tuke, Marcus A., additional, Deelen, Patrick, additional, Kristiansson, Kati, additional, Mattsson, Hannele, additional, Nõukas, Margit, additional, Sapkota, Yadav, additional, Schick, Ursula, additional, Porcu, Eleonora, additional, Rüeger, Sina, additional, McDaid, Aaron F., additional, Porteous, David, additional, Winkler, Thomas W., additional, Salvi, Erika, additional, Shrine, Nick, additional, Liu, Xueping, additional, Ang, Wei Q., additional, Zhang, Weihua, additional, Feitosa, Mary F., additional, Venturini, Cristina, additional, van der Most, Peter J., additional, Rosengren, Anders, additional, Wood, Andrew R., additional, Beaumont, Robin N., additional, Jones, Samuel E., additional, Ruth, Katherine S., additional, Yaghootkar, Hanieh, additional, Tyrrell, Jessica, additional, Havulinna, Aki S., additional, Boers, Harmen, additional, Mägi, Reedik, additional, Kriebel, Jennifer, additional, Müller-Nurasyid, Martina, additional, Perola, Markus, additional, Nieminen, Markku, additional, Lokki, Marja-Liisa, additional, Kähönen, Mika, additional, Viikari, Jorma S., additional, Geller, Frank, additional, Lahti, Jari, additional, Palotie, Aarno, additional, Koponen, Päivikki, additional, Lundqvist, Annamari, additional, Rissanen, Harri, additional, Bottinger, Erwin P., additional, Afaq, Saima, additional, Wojczynski, Mary K., additional, Lenzini, Petra, additional, Nolte, Ilja M., additional, Sparsø, Thomas, additional, Schupf, Nicole, additional, Christensen, Kaare, additional, Perls, Thomas T., additional, Newman, Anne B., additional, Werge, Thomas, additional, Snieder, Harold, additional, Spector, Timothy D., additional, Chambers, John C., additional, Koskinen, Seppo, additional, Melbye, Mads, additional, Raitakari, Olli T., additional, Lehtimäki, Terho, additional, Tobin, Martin D., additional, Wain, Louise V., additional, Sinisalo, Juha, additional, Peters, Annette, additional, Meitinger, Thomas, additional, Martin, Nicholas G., additional, Wray, Naomi R., additional, Montgomery, Grant W., additional, Medland, Sarah E., additional, Swertz, Morris A., additional, Vartiainen, Erkki, additional, Borodulin, Katja, additional, Männistö, Satu, additional, Murray, Anna, additional, Bochud, Murielle, additional, Jacquemont, Sébastien, additional, Rivadeneira, Fernando, additional, Hansen, Thomas F., additional, Oldehinkel, Albertine J., additional, Mangino, Massimo, additional, Province, Michael A., additional, Deloukas, Panos, additional, Kooner, Jaspal S., additional, Freathy, Rachel M., additional, Pennell, Craig, additional, Feenstra, Bjarke, additional, Strachan, David P., additional, Lettre, Guillaume, additional, Hirschhorn, Joel, additional, Cusi, Daniele, additional, Heid, Iris M., additional, Hayward, Caroline, additional, Männik, Katrin, additional, Beckmann, Jacques S., additional, Loos, Ruth J. F., additional, Nyholt, Dale R., additional, Metspalu, Andres, additional, Eriksson, Johan G., additional, Weedon, Michael N., additional, Salomaa, Veikko, additional, Franke, Lude, additional, Reymond, Alexandre, additional, Frayling, Timothy M., additional, and Kutalik, Zoltán, additional

Published
2017
Full Text
View/download PDF

170. Red blood cell distribution width: Genetic evidence for aging pathways in 116,666 volunteers

Author

Pilling, Luke C., primary, Atkins, Janice L., additional, Duff, Michael O., additional, Beaumont, Robin N., additional, Jones, Samuel E., additional, Tyrrell, Jessica, additional, Kuo, Chia-Ling, additional, Ruth, Katherine S., additional, Tuke, Marcus A., additional, Yaghootkar, Hanieh, additional, Wood, Andrew R., additional, Murray, Anna, additional, Weedon, Michael N., additional, Harries, Lorna W., additional, Kuchel, George A., additional, Ferrucci, Luigi, additional, Frayling, Timothy M., additional, and Melzer, David, additional

Published
2017
Full Text
View/download PDF

171. Mosaic Turner syndrome shows reduced phenotypic penetrance in an adult population study compared to clinically ascertained cases

Author

Tuke, Marcus A., primary, Ruth, Katherine S., additional, Wood, Andrew R., additional, Beaumont, Robin N., additional, Tyrrell, Jessica, additional, Jones, Samuel E., additional, Yaghootkar, Hanieh, additional, Turner, Claire L.S., additional, Donohoe, Mollie E., additional, Brooke, Antonia M., additional, Collinson, Morag N., additional, Freathy, Rachel M., additional, Weedon, Michael N., additional, Frayling, Timothy M., additional, and Murray, Anna, additional

Published
2017
Full Text
View/download PDF

174. Using genetics to understand the causal influence of higher BMI on depression.

Author

Tyrrell, Jessica, Mulugeta, Anwar, Wood, Andrew R, Zhou, Ang, Beaumont, Robin N, Tuke, Marcus A, Jones, Samuel E, Ruth, Katherine S, Yaghootkar, Hanieh, Sharp, Seth, Thompson, William D, Ji, Yingjie, Harrison, Jamie, Freathy, Rachel M, Murray, Anna, Weedon, Michael N, Lewis, Cathryn, Frayling, Timothy M, and Hyppönen, Elina

Subjects
RANDOMIZATION (Statistics), BODY mass index, GENETICS, STANDARD deviations, ODDS ratio, COMPARATIVE studies, MENTAL depression, RESEARCH methodology, MEDICAL cooperation, OBESITY, RESEARCH, RESEARCH funding, EVALUATION research
Abstract

Background: Depression is more common in obese than non-obese individuals, especially in women, but the causal relationship between obesity and depression is complex and uncertain. Previous studies have used genetic variants associated with BMI to provide evidence that higher body mass index (BMI) causes depression, but have not tested whether this relationship is driven by the metabolic consequences of BMI nor for differences between men and women.Methods: We performed a Mendelian randomization study using 48 791 individuals with depression and 291 995 controls in the UK Biobank, to test for causal effects of higher BMI on depression (defined using self-report and Hospital Episode data). We used two genetic instruments, both representing higher BMI, but one with and one without its adverse metabolic consequences, in an attempt to 'uncouple' the psychological component of obesity from the metabolic consequences. We further tested causal relationships in men and women separately, and using subsets of BMI variants from known physiological pathways.Results: Higher BMI was strongly associated with higher odds of depression, especially in women. Mendelian randomization provided evidence that higher BMI partly causes depression. Using a 73-variant BMI genetic risk score, a genetically determined one standard deviation (1 SD) higher BMI (4.9 kg/m2) was associated with higher odds of depression in all individuals [odds ratio (OR): 1.18, 95% confidence interval (CI): 1.09, 1.28, P = 0.00007) and women only (OR: 1.24, 95% CI: 1.11, 1.39, P = 0.0001). Meta-analysis with 45 591 depression cases and 97 647 controls from the Psychiatric Genomics Consortium (PGC) strengthened the statistical confidence of the findings in all individuals. Similar effect size estimates were obtained using different Mendelian randomization methods, although not all reached P < 0.05. Using a metabolically favourable adiposity genetic risk score, and meta-analysing data from the UK biobank and PGC, a genetically determined 1 SD higher BMI (4.9 kg/m2) was associated with higher odds of depression in all individuals (OR: 1.26, 95% CI: 1.06, 1.50], P = 0.010), but with weaker statistical confidence.Conclusions: Higher BMI, with and without its adverse metabolic consequences, is likely to have a causal role in determining the likelihood of an individual developing depression. [ABSTRACT FROM AUTHOR]

Published
2019
Full Text
View/download PDF

175. CNV-association meta-analysis in 191,161 European adults reveals new loci associated with anthropometric traits

Author

Macé, Aurélien, Tuke, Marcus A, Deelen, Patrick, Kristiansson, Kati, Mattsson, Hannele, Nõukas, Margit, Sapkota, Yadav, Schick, Ursula, Porcu, Eleonora, Rüeger, Sina, McDaid, Aaron F, Porteous, David, Winkler, Thomas W, Salvi, Erika, Shrine, Nick, Liu, Xueping, Ang, Wei Q, Zhang, Weihua, Feitosa, Mary F, Venturini, Cristina, van der Most, Peter J, Rosengren, Anders, Wood, Andrew R, Beaumont, Robin N, Jones, Samuel E, Ruth, Katherine S, Yaghootkar, Hanieh, Tyrrell, Jessica, Havulinna, Aki S, Boers, Harmen, Mägi, Reedik, Kriebel, Jennifer, Müller-Nurasyid, Martina, Perola, Markus, Nieminen, Markku, Lokki, Marja-Liisa, Kähönen, Mika, Viikari, Jorma S, Geller, Frank, Lahti, Jari, Palotie, Aarno, Koponen, Päivikki, Lundqvist, Annamari, Rissanen, Harri, Bottinger, Erwin P, Afaq, Saima, Wojczynski, Mary K, Lenzini, Petra, Nolte, Ilja M, Sparsø, Thomas, Schupf, Nicole, Christensen, Kaare, Perls, Thomas T, Newman, Anne B, Werge, Thomas, Snieder, Harold, Spector, Timothy D, Chambers, John C, Koskinen, Seppo, Melbye, Mads, Raitakari, Olli T, Lehtimäki, Terho, Tobin, Martin D, Wain, Louise V, Sinisalo, Juha, Peters, Annette, Meitinger, Thomas, Martin, Nicholas G, Wray, Naomi R, Montgomery, Grant W, Medland, Sarah E, Swertz, Morris A, Vartiainen, Erkki, Borodulin, Katja, Männistö, Satu, Murray, Anna, Bochud, Murielle, Jacquemont, Sébastien, Rivadeneira, Fernando, Hansen, Thomas F, Oldehinkel, Albertine J, Mangino, Massimo, Province, Michael A, Deloukas, Panos, Kooner, Jaspal S, Freathy, Rachel M, Pennell, Craig, Feenstra, Bjarke, Strachan, David P, Lettre, Guillaume, Hirschhorn, Joel, Cusi, Daniele, Heid, Iris M, Hayward, Caroline, Männik, Katrin, Beckmann, Jacques S, Loos, Ruth J F, Nyholt, Dale R, Metspalu, Andres, Eriksson, Johan G, Weedon, Michael N, Salomaa, Veikko, Franke, Lude, Reymond, Alexandre, Frayling, Timothy M, Kutalik, Zoltán, Macé, Aurélien, Tuke, Marcus A, Deelen, Patrick, Kristiansson, Kati, Mattsson, Hannele, Nõukas, Margit, Sapkota, Yadav, Schick, Ursula, Porcu, Eleonora, Rüeger, Sina, McDaid, Aaron F, Porteous, David, Winkler, Thomas W, Salvi, Erika, Shrine, Nick, Liu, Xueping, Ang, Wei Q, Zhang, Weihua, Feitosa, Mary F, Venturini, Cristina, van der Most, Peter J, Rosengren, Anders, Wood, Andrew R, Beaumont, Robin N, Jones, Samuel E, Ruth, Katherine S, Yaghootkar, Hanieh, Tyrrell, Jessica, Havulinna, Aki S, Boers, Harmen, Mägi, Reedik, Kriebel, Jennifer, Müller-Nurasyid, Martina, Perola, Markus, Nieminen, Markku, Lokki, Marja-Liisa, Kähönen, Mika, Viikari, Jorma S, Geller, Frank, Lahti, Jari, Palotie, Aarno, Koponen, Päivikki, Lundqvist, Annamari, Rissanen, Harri, Bottinger, Erwin P, Afaq, Saima, Wojczynski, Mary K, Lenzini, Petra, Nolte, Ilja M, Sparsø, Thomas, Schupf, Nicole, Christensen, Kaare, Perls, Thomas T, Newman, Anne B, Werge, Thomas, Snieder, Harold, Spector, Timothy D, Chambers, John C, Koskinen, Seppo, Melbye, Mads, Raitakari, Olli T, Lehtimäki, Terho, Tobin, Martin D, Wain, Louise V, Sinisalo, Juha, Peters, Annette, Meitinger, Thomas, Martin, Nicholas G, Wray, Naomi R, Montgomery, Grant W, Medland, Sarah E, Swertz, Morris A, Vartiainen, Erkki, Borodulin, Katja, Männistö, Satu, Murray, Anna, Bochud, Murielle, Jacquemont, Sébastien, Rivadeneira, Fernando, Hansen, Thomas F, Oldehinkel, Albertine J, Mangino, Massimo, Province, Michael A, Deloukas, Panos, Kooner, Jaspal S, Freathy, Rachel M, Pennell, Craig, Feenstra, Bjarke, Strachan, David P, Lettre, Guillaume, Hirschhorn, Joel, Cusi, Daniele, Heid, Iris M, Hayward, Caroline, Männik, Katrin, Beckmann, Jacques S, Loos, Ruth J F, Nyholt, Dale R, Metspalu, Andres, Eriksson, Johan G, Weedon, Michael N, Salomaa, Veikko, Franke, Lude, Reymond, Alexandre, Frayling, Timothy M, and Kutalik, Zoltán

Abstract

There are few examples of robust associations between rare copy number variants (CNVs) and complex continuous human traits. Here we present a large-scale CNV association meta-analysis on anthropometric traits in up to 191,161 adult samples from 26 cohorts. The study reveals five CNV associations at 1q21.1, 3q29, 7q11.23, 11p14.2, and 18q21.32 and confirms two known loci at 16p11.2 and 22q11.21, implicating at least one anthropometric trait. The discovered CNVs are recurrent and rare (0.01-0.2%), with large effects on height (>2.4 cm), weight (>5 kg), and body mass index (BMI) (>3.5 kg/m(2)). Burden analysis shows a 0.41 cm decrease in height, a 0.003 increase in waist-to-hip ratio and increase in BMI by 0.14 kg/m(2) for each Mb of total deletion burden (P = 2.5 × 10(-10), 6.0 × 10(-5), and 2.9 × 10(-3)). Our study provides evidence that the same genes (e.g., MC4R, FIBIN, and FMO5) harbor both common and rare variants affecting body size and that anthropometric traits share genetic loci with developmental and psychiatric disorders.Individual SNPs have small effects on anthropometric traits, yet the impact of CNVs has remained largely unknown. Here, Kutalik and co-workers perform a large-scale genome-wide meta-analysis of structural variation and find rare CNVs associated with height, weight and BMI with large effect sizes.

Published
2017

176. Height, body mass index, and socioeconomic status: mendelian randomisation study in UK Biobank

Author

Broad Institute of MIT and Harvard, Hirschhorn, Joel N, Tyrrell, Jessica, Jones, Samuel E, Beaumont, Robin, Astley, Christina M, Lovell, Rebecca, Yaghootkar, Hanieh, Tuke, Marcus, Ruth, Katherine S, Freathy, Rachel M, Wood, Andrew R, Murray, Anna, Weedon, Michael N, Frayling, Timothy M, Broad Institute of MIT and Harvard, Hirschhorn, Joel N, Tyrrell, Jessica, Jones, Samuel E, Beaumont, Robin, Astley, Christina M, Lovell, Rebecca, Yaghootkar, Hanieh, Tuke, Marcus, Ruth, Katherine S, Freathy, Rachel M, Wood, Andrew R, Murray, Anna, Weedon, Michael N, and Frayling, Timothy M

Abstract

Objective To determine whether height and body mass index (BMI) have a causal role in five measures of socioeconomic status. Design Mendelian randomisation study to test for causal effects of differences in stature and BMI on five measures of socioeconomic status. Mendelian randomisation exploits the fact that genotypes are randomly assigned at conception and thus not confounded by non-genetic factors. Setting UK Biobank. Participants 119,669 men and women of British ancestry, aged between 37 and 73 years. Main outcome measures Age completed full time education, degree level education, job class, annual household income, and Townsend deprivation index. Results In the UK Biobank study, shorter stature and higher BMI were observationally associated with several measures of lower socioeconomic status. The associations between shorter stature and lower socioeconomic status tended to be stronger in men, and the associations between higher BMI and lower socioeconomic status tended to be stronger in women. For example, a 1 standard deviation (SD) higher BMI was associated with a £210 (€276; $300; 95% confidence interval £84 to £420; P=6×10⁻³) lower annual household income in men and a £1890 (£1680 to £2100; P=6×10⁻¹⁵) lower annual household income in women. Genetic analysis provided evidence that these associations were partly causal. A genetically determined 1 SD (6.3 cm) taller stature caused a 0.06 (0.02 to 0.09) year older age of completing full time education (P=0.01), a 1.12 (1.07 to 1.18) times higher odds of working in a skilled profession (P=6×10⁻⁷), and a £1130 (£680 to £1580) higher annual household income (P=4×10⁻⁸). Associations were stronger in men. A genetically determined 1 SD higher BMI (4.6 kg/m2) caused a £2940 (£1680 to £4200; P=1×10⁻⁵) lower annual household income and a 0.10 (0.04 to 0.16) SD (P=0.001) higher level of deprivation in women only. Conclusions These data support evidence that height and BMI play an important partial role in deter

Published
2017

177. Response to Prakash et al.

Author

Tuke, Marcus A., Ruth, Katherine S., Wood, Andrew R., Beaumont, Robin N., Tyrrell, Jessica, Jones, Samuel E., Yaghootkar, Hanieh, Turner, Claire L.S., Donohoe, Mollie E., Brooke, Antonia M., Collinson, Morag N., Freathy, Rachel M., Weedon, Michael N., Frayling, Timothy M., and Murray, Anna

Published
2019
Full Text
View/download PDF

178. Gene–obesogenic environment interactions in the UK Biobank study

Author

Tyrrell, Jessica, primary, Wood, Andrew R, additional, Ames, Ryan M, additional, Yaghootkar, Hanieh, additional, Beaumont, Robin N, additional, Jones, Samuel E, additional, Tuke, Marcus A, additional, Ruth, Katherine S, additional, Freathy, Rachel M, additional, Davey Smith, George, additional, Joost, Stéphane, additional, Guessous, Idris, additional, Murray, Anna, additional, Strachan, David P, additional, Kutalik, Zoltán, additional, Weedon, Michael N, additional, and Frayling, Timothy M, additional

Published
2017
Full Text
View/download PDF

179. Quantifying the extent to which index event biases influence large genetic association studies

Author

Yaghootkar, Hanieh, primary, Bancks, Michael P., additional, Jones, Sam E., additional, McDaid, Aaron, additional, Beaumont, Robin, additional, Donnelly, Louise, additional, Wood, Andrew R., additional, Campbell, Archie, additional, Tyrrell, Jessica, additional, Hocking, Lynne J., additional, Tuke, Marcus A., additional, Ruth, Katherine S., additional, Pearson, Ewan R., additional, Murray, Anna, additional, Freathy, Rachel M., additional, Munroe, Patricia B., additional, Hayward, Caroline, additional, Palmer, Colin, additional, Weedon, Michael N., additional, Pankow, James S., additional, Frayling, Timothy M., additional, and Kutalik, Zoltán, additional

Published
2016
Full Text
View/download PDF

180. Evidence that lower socioeconomic position accentuates genetic susceptibility to obesity

Author

Tyrrell, Jessica, primary, Wood, Andrew R, additional, Ames, Ryan M, additional, Yaghootkar, Hanieh, additional, Beaumont, Robin N., additional, Jones, Samuel E., additional, Tuke, Marcus A, additional, Ruth, Katherine S., additional, Freathy, Rachel M, additional, Smith, George Davey, additional, Joost, Stéphane, additional, Guessous, Idris, additional, Murray, Anna, additional, Strachan, David P., additional, Kutalik, Zoltán, additional, Weedon, Michael N, additional, and Frayling, Timothy M, additional

Published
2016
Full Text
View/download PDF

181. Genetic Evidence for a Link Between Favorable Adiposity and Lower Risk of Type 2 Diabetes, Hypertension, and Heart Disease

Author

Yaghootkar, Hanieh, primary, Lotta, Luca A., additional, Tyrrell, Jessica, additional, Smit, Roelof A.J., additional, Jones, Sam E., additional, Donnelly, Louise, additional, Beaumont, Robin, additional, Campbell, Archie, additional, Tuke, Marcus A., additional, Hayward, Caroline, additional, Ruth, Katherine S., additional, Padmanabhan, Sandosh, additional, Jukema, J. Wouter, additional, Palmer, Colin C., additional, Hattersley, Andrew, additional, Freathy, Rachel M., additional, Langenberg, Claudia, additional, Wareham, Nicholas J., additional, Wood, Andrew R., additional, Murray, Anna, additional, Weedon, Michael N., additional, Sattar, Naveed, additional, Pearson, Ewan, additional, Scott, Robert A., additional, and Frayling, Timothy M., additional

Published
2016
Full Text
View/download PDF

182. Human longevity is influenced by many genetic variants: evidence from 75,000 UK Biobank participants

Author

Pilling, Luke C., primary, Atkins, Janice L., additional, Bowman, Kirsty, additional, Jones, Samuel E., additional, Tyrrell, Jessica, additional, Beaumont, Robin N., additional, Ruth, Katherine S., additional, Tuke, Marcus A., additional, Yaghootkar, Hanieh, additional, Wood, Andrew R., additional, Freathy, Rachel M., additional, Murray, Anna, additional, Weedon, Michael N., additional, Xue, Luting, additional, Lunetta, Kathryn, additional, Murabito, Joanne M., additional, Harries, Lorna W., additional, Robine, Jean-Marie, additional, Brayne, Carol, additional, Kuchel, George A., additional, Ferrucci, Luigi, additional, Frayling, Timothy M., additional, and Melzer, David, additional

Published
2016
Full Text
View/download PDF

183. Introduction: Chiismes politiques.

Author

Beaumont, Robin and Calabrese, Erminia Chiara

Abstract

The article discusses the polarization of the Arab world and the intensification of a transnational conflict between Sunni and Shiite Islam. It notes that a symmetrical movement opposing the fragmentation of Islam Sunni unified the rise of Shiism. It adds that the Shiite political Islam, led by the new regional hegemonic Iran, would be supported by the same historical movement, especially in the military victories, in Iraq and Syria.

Published
2019

184. Genome-Wide and Abdominal MRI Data Provide Evidence That a Genetically Determined Favorable Adiposity Phenotype Is Characterized by Lower Ectopic Liver Fat and Lower Risk of Type 2 Diabetes, Heart Disease, and Hypertension.

Author

Yingjie Ji, Yiorkas, Andrianos M., Frau, Francesca, Mook-Kanamori, Dennis, Staiger, Harald, Thomas, E.Louise, Atabaki-Pasdar, Naeimeh, Campbell, Archie, Tyrrell, Jessica, Jones, Samuel E., Beaumont, Robin N., Wood, Andrew R., Tuke, Marcus A., Ruth, Katherine S., Mahajan, Anubha, Murray, Anna, Freathy, Rachel M., Weedon, Michael N., Hattersley, Andrew T., and Hayward, Caroline

Subjects
TYPE 2 diabetes, MAGNETIC resonance imaging, FATTY liver, HEART disease risk factors, DIABETES risk factors, HYPERTENSION, ADIPOSE tissues, ADIPOSE tissue physiology, COMPARATIVE studies, HEART diseases, RESEARCH methodology, MEDICAL cooperation, OBESITY, RESEARCH, RESEARCH funding, EVALUATION research, WAIST-hip ratio, SEQUENCE analysis
Abstract

Recent genetic studies have identified alleles associated with opposite effects on adiposity and risk of type 2 diabetes. We aimed to identify more of these variants and test the hypothesis that such favorable adiposity alleles are associated with higher subcutaneous fat and lower ectopic fat. We combined MRI data with genome-wide association studies of body fat percentage (%) and metabolic traits. We report 14 alleles, including 7 newly characterized alleles, associated with higher adiposity but a favorable metabolic profile. Consistent with previous studies, individuals carrying more favorable adiposity alleles had higher body fat % and higher BMI but lower risk of type 2 diabetes, heart disease, and hypertension. These individuals also had higher subcutaneous fat but lower liver fat and a lower visceral-to-subcutaneous adipose tissue ratio. Individual alleles associated with higher body fat % but lower liver fat and lower risk of type 2 diabetes included those in PPARG, GRB14, and IRS1, whereas the allele in ANKRD55 was paradoxically associated with higher visceral fat but lower risk of type 2 diabetes. Most identified favorable adiposity alleles are associated with higher subcutaneous and lower liver fat, a mechanism consistent with the beneficial effects of storing excess triglycerides in metabolically low-risk depots. [ABSTRACT FROM AUTHOR]

Published
2019
Full Text
View/download PDF

185. Meta-analysis of genome-wide association studies for body fat distribution in 694 649 individuals of European ancestry.

Author

Pulit, Sara L, Stoneman, Charli, Morris, Andrew P, Wood, Andrew R, Glastonbury, Craig A, Tyrrell, Jessica, Yengo, Loïc, Ferreira, Teresa, Marouli, Eirini, Ji, Yingjie, Yang, Jian, Jones, Samuel, Beaumont, Robin, Croteau-Chonka, Damien C, Winkler, Thomas W, Consortium, GIANT, Hattersley, Andrew T, Loos, Ruth J F, Hirschhorn, Joel N, and Visscher, Peter M

Published
2019
Full Text
View/download PDF

186. 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, Beaumont, Robin N, Wittemans, Laura, Martin, Susan, Busch, Alexander S., Erzurumluoglu, A. Mesut, Hollis, Benjamin, O’Mara, Tracy A., McCarthy, Mark I, Langenberg, Claudia, Easton, Douglas F, Wareham, Nicholas J, Burgess, Stephen, Murray, Anna, Ong, Ken K, Frayling, Timothy M, and Perry, John R. B.

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.

Published
2020
Full Text
View/download PDF

187. Biological and clinical insights from genetics of insomnia symptoms

Author

Lane, Jacqueline M., Jones, Samuel E., Dashti, Hassan S., Wood, Andrew R., Aragam, Krishna G., van Hees, Vincent T., Strand, Linn B., Winsvold, Bendik S., Wang, Heming, Bowden, Jack, Song, Yanwei, Patel, Krunal, Anderson, Simon G., Beaumont, Robin N., Bechtold, David A., Cade, Brian E., Haas, Mary, Kathiresan, Sekar, Little, Max A., Luik, Annemarie I., Loudon, Andrew S., Purcell, Shaun, Richmond, Rebecca C., Scheer, Frank A. J. L., Schormair, Barbara, Tyrrell, Jessica, Winkelman, John W., Winkelmann, Juliane, Hveem, Kristian, Zhao, Chen, Nielsen, Jonas B., Willer, Cristen J., Redline, Susan, Spiegelhalder, Kai, Kyle, Simon D., Ray, David W., Zwart, John-Anker, Brumpton, Ben, Frayling, Timothy M., Lawlor, Deborah A., Rutter, Martin K., Weedon, Michael N., and Saxena, Richa

Abstract

Insomnia is a common disorder linked with adverse long-term medical and psychiatric outcomes. The underlying pathophysiological processes and causal relationships of insomnia with disease are poorly understood. Here we identified 57 loci for self-reported insomnia symptoms in the UK Biobank (n = 453,379) and confirmed their effects on self-reported insomnia symptoms in the HUNT Study (n = 14,923 cases and 47,610 controls), physician-diagnosed insomnia in the Partners Biobank (n = 2,217 cases and 14,240 controls), and accelerometer-derived measures of sleep efficiency and sleep duration in the UK Biobank (n = 83,726). Our results suggest enrichment of genes involved in ubiquitin-mediated proteolysis and of genes expressed in multiple brain regions, skeletal muscle, and adrenal glands. Evidence of shared genetic factors was found between frequent insomnia symptoms and restless legs syndrome, aging, and cardiometabolic, behavioral, psychiatric, and reproductive traits. Evidence was found for a possible causal link between insomnia symptoms and coronary artery disease, depressive symptoms, and subjective well-being.

Published
2019
Full Text
View/download PDF

188. Genome-wide association analyses in >119,000 individuals identifies thirteen morningness and two sleep duration loci

Author

Jones, Samuel E, primary, Tyrrell, Jessica, additional, Wood, Andrew R, additional, Beaumont, Robin N, additional, Ruth, Katherine S, additional, Tuke, Marcus A, additional, Yaghootkar, Hanieh, additional, Hu, Youna, additional, Teder-Laving, Maris, additional, Hayward, Caroline, additional, Roenneberg, Till, additional, Wilson, James F, additional, Del Greco, Fabiola, additional, Hicks, Andrew A, additional, Shin, Chol, additional, Yun, Chang-Ho, additional, Ku Lee, Seung, additional, Metspalu, Andres, additional, Byrne, Enda M, additional, Gehrman, Philip R, additional, Tiemeier, Henning, additional, Allebrandt, Karla V, additional, Freathy, Rachel M, additional, Murray, Anna, additional, Hinds, David A, additional, Frayling, Timothy M, additional, and Weedon, Michael N, additional

Published
2016
Full Text
View/download PDF

189. HUMAN LONGEVITY IS INFLUENCED BY MANY GENETIC VARIANTS: EVIDENCE FROM 75,000 UK BIOBANK PARTICIPANTS

Author

Pilling, Luke C, primary, Atkins, Janice L, additional, Bowman, Kirsty, additional, Jones, Samuel E, additional, Tyrrell, Jessica, additional, Beaumont, Robin N, additional, Ruth, Katherine S, additional, Tuke, Marcus A, additional, Yaghootkar, Hanieh, additional, Wood, Andrew R, additional, Freathy, Rachel M, additional, Murray, Anna, additional, Weedon, Michael N, additional, Xue, Luting, additional, Lunetta, Kathryn, additional, Murabito, Joanne M, additional, Harries, Lorna W, additional, Robine, Jean-Marie, additional, Brayne, Carol, additional, Kuchel, George A, additional, Ferrucci, Luigi, additional, Frayling, Timothy M, additional, and Melzer, David, additional

Published
2016
Full Text
View/download PDF

191. Genetic evidence that lower circulating FSH levels lengthen menstrual cycle, increase age at menopause, and impact reproductive health: a UK Biobank study

Author

Ruth, Katherine S, primary, Beaumont, Robin N, additional, Tyrrell, Jessica, additional, Jones, Samuel E, additional, Tuke, Marcus A, additional, Yaghootkar, Hanieh, additional, Wood, Andrew R, additional, Freathy, Rachel M, additional, Weedon, Michael N, additional, Frayling, Timothy M, additional, and Murray, Anna, additional

Published
2015
Full Text
View/download PDF

193. Variants in the FTO and CDKAL1 loci have recessive effects on risk of obesity and type 2 diabetes, respectively.

Author

Wood, Andrew, Tyrrell, Jessica, Beaumont, Robin, Jones, Samuel, Tuke, Marcus, Ruth, Katherine, Yaghootkar, Hanieh, Freathy, Rachel, Murray, Anna, Frayling, Timothy, and Weedon, Michael

Abstract

Aims/hypothesis: Genome-wide association (GWA) studies have identified hundreds of common genetic variants associated with obesity and type 2 diabetes. These studies have usually focused on additive association tests. Identifying deviations from additivity may provide new biological insights and explain some of the missing heritability for these diseases. Methods: We performed a GWA study using a dominance deviation model for BMI, obesity (29,925 cases) and type 2 diabetes (4,040 cases) in 120,286 individuals of British ancestry from the UK Biobank study. We also investigated whether single nucleotide polymorphisms previously shown to be associated with these traits showed any enrichment for departures from additivity. Results: Known obesity-associated variants in FTO showed strong evidence of deviation from additivity ( p = 3 × 10) through a recessive effect of the allele associated with higher BMI. The average BMI of individuals carrying zero, one or two BMI-raising alleles was 27.27 (95% CI 27.22, 27.31) kg/m, 27.54 (95% CI 27.50, 27.58) kg/m and 28.07 (95% CI 28.00, 28.14) kg/m, respectively. A similar effect was observed in 105,643 individuals from the GIANT Consortium ( p = 0.003; meta-analysis p = 1 × 10). For type 2 diabetes, we detected a recessive effect ( p = 5 × 10) at CDKAL1. Relative to homozygous non-risk allele carriers, homozygous risk allele carriers had an OR of 1.48 (95% CI 1.32, 1.65), while the heterozygous group had an OR of 1.06 (95% CI 0.99, 1.14), a result consistent with that of a previous study. We did not identify any novel associations at genome-wide significance. Conclusions/interpretation: Although we found no evidence of widespread non-additive genetic effects contributing to obesity and type 2 diabetes risk, we did find robust examples of recessive effects at the FTO and CDKAL1 loci. Access to research materials: Summary statistics are available at and by request (a.r.wood@exeter.ac.uk). All underlying data are available on application from the UK Biobank. [ABSTRACT FROM AUTHOR]

Published
2016
Full Text
View/download PDF

194. Author Correction: Genetic effects on the timing of parturition and links to fetal birth weight

Author

Solé-Navais, Pol, Flatley, Christopher, Steinthorsdottir, Valgerdur, Vaudel, Marc, Juodakis, Julius, Chen, Jing, Laisk, Triin, LaBella, Abigail L., Westergaard, David, Bacelis, Jonas, Brumpton, Ben, Skotte, Line, Borges, Maria C., Helgeland, Øyvind, Mahajan, Anubha, Wielscher, Matthias, Lin, Frederick, Briggs, Catherine, Wang, Carol A., Moen, Gunn-Helen, Beaumont, Robin N., Bradfield, Jonathan P., Abraham, Abin, Thorleifsson, Gudmar, Gabrielsen, Maiken E., Ostrowski, Sisse R., Modzelewska, Dominika, Nohr, Ellen A., Hypponen, Elina, Srivastava, Amit, Talbot, Octavious, Allard, Catherine, Williams, Scott M., Menon, Ramkumar, Shields, Beverley M., Sveinbjornsson, Gardar, Xu, Huan, Melbye, Mads, Lowe, William, Bouchard, Luigi, Oken, Emily, Pedersen, Ole B., Gudbjartsson, Daniel F., Erikstrup, Christian, Sørensen, Erik, Lie, Rolv T., Teramo, Kari, Hallman, Mikko, Juliusdottir, Thorhildur, Hakonarson, Hakon, Ullum, Henrik, Hattersley, Andrew T., Sletner, Line, Merialdi, Mario, Rifas-Shiman, Sheryl L., Steingrimsdottir, Thora, Scholtens, Denise, Power, Christine, West, Jane, Nyegaard, Mette, Capra, John A., Skogholt, Anne H., Magnus, Per, Andreassen, Ole A., Thorsteinsdottir, Unnur, Grant, Struan F. A., Qvigstad, Elisabeth, Pennell, Craig E., Hivert, Marie-France, Hayes, Geoffrey M., Jarvelin, Marjo-Riitta, McCarthy, Mark I., Lawlor, Deborah A., Nielsen, Henriette S., Mägi, Reedik, Rokas, Antonis, Hveem, Kristian, Stefansson, Kari, Feenstra, Bjarke, Njolstad, Pål, Muglia, Louis J., Freathy, Rachel M., Johansson, Stefan, Zhang, Ge, and Jacobsson, Bo

Published
2023
Full Text
View/download PDF

196. Letters.

Author

Barth, Julian H, Jones, Richard G, Bachmann, Lucas M, Steurer, Johann, ter Riet, Gerben, Emery, Jon D, Purves, Ian N, Beaumont, Robin, Mitchell, Liz, Sullivan, Frank, Montgomery, Alan, Gregor, Peter, van Wyk, Jacobus T, Moorman, Peter W, van Wijk, Marc A M, Eccles, Martin P, McColl, Elaine, Steen, Nick, Rousseau, Nikki, and Grimshaw, Jeremy

Subjects
LETTERS to the editor, MEDICINE, CLINICAL medicine, DISEASES, COMMUNICABLE diseases, MARRIED people
Abstract

Presents letters to the editor of the 'British Medical Journal'. How indiscriminate investigations have adverse effects; Statement that simple presentation of test accuracy may lead to inflated disease probabilities; How assortative mating may explain spouses' risk of same disease; Others.

Published
2003

198. Detection and characterization of male sex chromosome abnormalities in the UK Biobank study

Author

Zhao, Yajie, Gardner, Eugene J., Tuke, Marcus A., Zhang, Huairen, Pietzner, Maik, Koprulu, Mine, Jia, Raina Y., Ruth, Katherine S., Wood, Andrew R., Beaumont, Robin N., Tyrrell, Jessica, Jones, Samuel E., Allen, Hana Lango, Day, Felix R., Langenberg, Claudia, Frayling, Timothy M., Weedon, Michael N., Perry, John R.B., Ong, Ken K., and Murray, Anna

Abstract

The study aimed to systematically ascertain male sex chromosome abnormalities, 47,XXY (Klinefelter syndrome [KS]) and 47,XYY, and characterize their risks of adverse health outcomes.

Published
2022
Full Text
View/download PDF

199. Variants in the fetal genome near pro-inflammatory cytokine genes on 2q13 associate with gestational duration.

Author

Liu, Xueping, Helenius, Dorte, Skotte, Line, Beaumont, Robin N., Wielscher, Matthias, Geller, Frank, Juodakis, Julius, Mahajan, Anubha, Bradfield, Jonathan P., Lin, Frederick T. J., Vogelezang, Suzanne, Bustamante, Mariona, Ahluwalia, Tarunveer S., Pitkänen, Niina, Wang, Carol A., Bacelis, Jonas, Borges, Maria C., Zhang, Ge, Bedell, Bruce A., and Rossi, Robert M.

Subjects
DURATION of pregnancy, PARTURITION, GENOMES, GENES, PREGNANCY
Abstract

The duration of pregnancy is influenced by fetal and maternal genetic and non-genetic factors. Here we report a fetal genome-wide association meta-analysis of gestational duration, and early preterm, preterm, and postterm birth in 84,689 infants. One locus on chromosome 2q13 is associated with gestational duration; the association is replicated in 9,291 additional infants (combined P = 3.96 × 10−14). Analysis of 15,588 mother-child pairs shows that the association is driven by fetal rather than maternal genotype. Functional experiments show that the lead SNP, rs7594852, alters the binding of the HIC1 transcriptional repressor. Genes at the locus include several interleukin 1 family members with roles in pro-inflammatory pathways that are central to the process of parturition. Further understanding of the underlying mechanisms will be of great public health importance, since giving birth either before or after the window of term gestation is associated with increased morbidity and mortality. Gestational duration depends on both maternal and fetal genetic influences. Here, the authors perform a fetal genome-wide association meta-analysis and find that a locus on 2q13 is associated with pregnancy duration and further show that the lead SNP rs7594852 changes the binding properties of transcriptional repressor HIC1. [ABSTRACT FROM AUTHOR]

Published
2019
Full Text
View/download PDF

200. 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., and Murray, Anna

Abstract

Sleep is an essential human function but its regulation is poorly understood. Using accelerometer data from 85,670 UK Biobank participants, we perform a genome-wide association study of 8 derived sleep traits representing sleep quality, quantity and timing, and validate our findings in 5,819 individuals. We identify 47 genetic associations at P < 5 × 10−8, of which 20 reach a stricter threshold of P < 8 × 10−10. These include 26 novel associations with measures of sleep quality and 10 with nocturnal sleep duration. The majority of identified variants associate with a single sleep trait, except for variants previously associated with restless legs syndrome. For sleep duration we identify a missense variant (p.Tyr727Cys) in PDE11A as the likely causal variant. As a group, sleep quality loci are enriched for serotonin processing genes. Although accelerometer-derived measures of sleep are imperfect and may be affected by restless legs syndrome, these findings provide new biological insights into sleep compared to previous efforts based on self-report sleep measures. Quality, quantity and timing of sleep are important factors for overall human health. Here, the authors perform GWAS for sleep traits estimated using wearable accelerometers and identify 47 genetic associations, including 26 novel associations for measures of sleep quality and 10 for nocturnal sleep duration. [ABSTRACT FROM AUTHOR]

Published
2019
Full Text
View/download PDF

Catalog

Books, media, physical & digital resources
See catalog results