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201. Genetics

Author

Holloway, John W., primary and Holgate, Stephen T., additional

Published
2004
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205. GWAS on longitudinal growth traits reveals different genetic factors influencing infant, child, and adult BMI

Author

Da Silva Couto Alves, Alexessander, De Silva, N. Maneka G., Karhunen, Ville, Sovio, Ulla, Das, Shikta, Taal, H. Rob, Warrington, Nicole M., Lewin, Alexandra M., Kaakinen, Marika, Cousminer, Diana L., Thiering, Elisabeth, Timpson, Nicholas J., Bond, Tom A., Lowry, Estelle, Brown, Christopher D., Estivill, Xavier, Lindi, Virpi, Bradfield, Jonathan P., Geller, Frank, Speed, Doug, Coin, Lachlan J. M., Loh, Marie, Barton, Sheila J., Beilin, Lawrence J., Bisgaard, Hans, Bonnelykke, Klaus, Alili, Rohia, Hatoum, Ida J., Schramm, Katharina, Cartwright, Rufus, Charles, Marie-Aline, Salerno, Vincenzo, Clement, Karine, Claringbould, Annique A.J, Consortium, BIOS, van Duijin, Cornelia M., Moltchanova, Elena, Eriksson, Johan G., Elks, Cathy, Feenstra, Bjarke, Flexeder, Claudia, Franks, Stephen, Frayling, Timothy M., Freathy, Rachel M., Elliot, Paul, Widen, Elisabeth, Hakonarson, Hakon, Hattersley, Andrew T., Rodriguez, Alina, Banterle, Marco, Heinrich, Joachim, Heude, Barbara, Holloway, John W., Hofman, Albert, Hypponen, Elina, Inskip, Hazel, Kaplan, Lee M., Hedman, Asa K., Laara, Esa, Prokisch, Holger, Grallert, Harald, Lakka, Timo A., Lawlor, Debbie A., Melbye, Mads, Ahluwalia, Tarunveer S., Marinelli, Marcella, Millwood, Iona Y., Palmer, Lyle J., Pennell, Craig E., Perry, John R., Ring, Susan M., Savolainen, Markku J., Rivadeneira, Fernando, Standl, Marie, Sunyer, Jordi, Tiesler, Carla M.T, Uitterlinden, Andre G., Schierding, William, O'Sullivan, Justin M., Prokopenko, Inga, Herzig, Karl-Heinz, Smith, George Davey, O'Reilly, Paul, Felix, Janine F., Buxton, Jessica L., Blakemore, Alexandra L. F, Ong, Ken K., Jaddoe, Vincent W.V, Grant, Struan F.A, Sebert, Sylvain, McCarthy, Mark L., and Jarvelin, Marjo-Riitta

Abstract

Early childhood growth patterns are associated with adult health, yet the genetic factors and the developmental stages involved are not fully understood. Here, we combine genome-wide association studies with modeling of longitudinal growth traits to study the genetics of infant and child growth, followed by functional, pathway, genetic correlation, risk score, and colocalization analyses to determine how developmental timings, molecular pathways, and genetic determinants of these traits overlap with those of adult health. We found a robust overlap between the genetics of child and adult body mass index (BMI), with variants associated with adult BMI acting as early as 4 to 6 years old. However, we demonstrated a completely distinct genetic makeup for peak BMI during infancy, influenced by variation at the LEPR/LEPROT locus. These findings suggest that different genetic factors control infant and child BMI. In light of the obesity epidemic, these findings are important to inform the timing and targets of prevention strategies.

Published
2019

206. The Early Growth Genetics (EGG) and EArly Genetics and Lifecourse Epidemiology (EAGLE) consortia

Author

Middeldorp, Christel M., Mahajan, Anubha, Horikoshi, Momoko, Robertson, Neil R., Beaumont, Robin N., Bradfield, Jonathan P., Bustamante, Mariona, Cousminer, Diana L., Day, Felix R., De Silva, N. Maneka, Guxens, Monica, Mook-Kanamori, Dennis O., St Pourcain, Beate, Warrington, Nicole M., Adair, Linda S., Ahlqvist, Emma, Ahluwalia, Tarunveer Singh, Almgren, Peter, Ang, Wei, Atalay, Mustafa, Auvinen, Juha, Bartels, Meike, Beckmann, Jacques S., Bilbao, Jose Ramon, Bond, Tom, Borja, Judith B., Cavadino, Alana, Charoen, Pimphen, Chen, Zhanghua, Coin, Lachlan, Cooper, Cyrus, Curtin, John A., Custovic, Adnan, Das, Shikta, Davies, Gareth E., Dedoussis, George V., Duijts, Liesbeth, Eastwood, Peter R., Eliasen, Anders U., Elliott, Paul, Eriksson, Johan G., Estivill, Xavier, Fadista, Joao, Fedko, Iryna O., Frayling, Timothy M., Gaillard, Romy, Gauderman, W. James, Geller, Frank, Gilliland, Frank, Gilsanz, Vincente, Granell, Raquel, Grarup, Niels, Groop, Leif, Hadley, Dexter, Hakonarson, Hakon, Hansen, Torben, Hartman, Catharina A., Hattersley, Andrew T., Hayes, M. Geoffrey, Hebebrand, Johannes, Heinrich, Joachim, Helgeland, Oyvind, Henders, Anjali K., Henderson, John, Henriksen, Tine B., Hirschhorn, Joel N., Hivert, Marie-France, Hocher, Berthold, Holloway, John W., Holt, Patrick, Hottenga, Jouke-Jan, Hypponen, Elina, Iniguez, Carmen, Johansson, Stefan, Jugessur, Astanand, Kahonen, Mika, Kalkwarf, Heidi J., Kaprio, Jaakko, Karhunen, Ville, Kemp, John P., Kerkhof, Marjan, Koppelman, Gerard H., Korner, Antje, Kotecha, Sailesh, Kreiner-Moller, Eskil, Kulohoma, Benard, Kumar, Ashish, Kutalik, Zoltan, Lahti, Jari, Lappe, Joan M., Larsson, Henrik, Lehtimaki, Terho, Lewin, Alexandra M., Li, Jin, Lichtenstein, Paul, Lindgren, Cecilia M., Lindi, Virpi, Linneberg, Allan, Liu, Xueping, Liu, Jun, Lowe, William L., Lundstrom, Sebastian, Lyytikainen, Leo-Pekka, Ma, Ronald C. W., Mace, Aurelien, Magi, Reedik, Magnus, Per, Mamun, Abdullah A., Mannikko, Minna, Martin, Nicholas G., Mbarek, Hamdi, McCarthy, Nina S., Medland, Sarah E., Melbye, Mads, Melen, Erik, Mohlke, Karen L., Monnereau, Claire, Morgen, Camilla S., Morris, Andrew P., Murray, Jeffrey C., Myhre, Ronny, Najman, Jackob M., Nivard, Michel G., Nohr, Ellen A., Nolte, Ilja M., Ntalla, Ioanna, Oberfield, Sharon E., Oken, Emily, Oldehinkel, Albertine J., Pahkala, Katja, Palviainen, Teemu, Panoutsopoulou, Kalliope, Pedersen, Oluf, Pennell, Craig E., Pershagen, Goran, Pitkanen, Niina, Plomin, Robert, Power, Christine, Prasad, Rashmi B., Prokopenko, Inga, Pulkkinen, Lea, Raikkonen, Katri, Raitakari, Olli T., Reynolds, Rebecca M., Richmond, Rebecca C., Rivadeneira, Fernando, Rodriguez, Alina, Rose, Richard J., Salem, Rany, Santa-Marina, Loreto, Saw, Seang-Mei, Schnurr, Theresia M., Scott, James G., Selzam, Saskia, Shepherd, John A., Simpson, Angela, Skotte, Line, Sleiman, Patrick M. A., Snieder, Harold, Sorensen, Thorkild I. A., Standl, Marie, Steegers, Eric A. P., Strachan, David P., Straker, Leon, Strandberg, Timo, Taylor, Michelle, Teo, Yik-Ying, Thiering, Elisabeth, Torrent, Maties, Tyrrell, Jessica, Uitterlinden, Andre G., van Beijsterveldt, Toos, van der Most, Peter J., van Duijn, Cornelia M., Viikari, Jorma, Vilor-Tejedor, Natalia, Vogelezang, Suzanne, Vonk, Judith M., Vrijkotte, Tanja G. M., Vuoksimaa, Eero, Wang, Carol A., Watkins, William J., Wichmann, H-Erich, Willemsen, Gonneke, Williams, Gail M., Wilson, James F., Wray, Naomi R., Xu, Shujing, Xu, Cheng-Jian, Yaghootkar, Hanieh, Yi, Lu, Zafarmand, Mohammad Hadi, Zeggini, Eleftheria, Zemel, Babette S., Hinney, Anke, Lakka, Timo A., Whitehouse, Andrew J. O., Sunyer, Jordi, Widen, Elisabeth E., Feenstra, Bjarke, Sebert, Sylvain, Jacobsson, Bo, Njolstad, Pal R., Stoltenberg, Camilla, Smith, George Davey, Lawlor, Debbie A., Paternoster, Lavinia, Timpson, Nicholas J., Ong, Ken K., Bisgaard, Hans, Bonnelykke, Klaus, Jaddoe, Vincent W. V., Tiemeier, Henning, Jarvelin, Marjo-Riitta, Evans, David M., Perry, John R. B., Grant, Struan F. A., Boomsma, Dorret I., Freathy, Rachel M., McCarthy, Mark I., and Felix, Janine F.

Subjects
ddc:570, Institut für Biochemie und Biologie
Abstract

The impact of many unfavorable childhood traits or diseases, such as low birth weight and mental disorders, is not limited to childhood and adolescence, as they are also associated with poor outcomes in adulthood, such as cardiovascular disease. Insight into the genetic etiology of childhood and adolescent traits and disorders may therefore provide new perspectives, not only on how to improve wellbeing during childhood, but also how to prevent later adverse outcomes. To achieve the sample sizes required for genetic research, the Early Growth Genetics (EGG) and EArly Genetics and Lifecourse Epidemiology (EAGLE) consortia were established. The majority of the participating cohorts are longitudinal population-based samples, but other cohorts with data on early childhood phenotypes are also involved. Cohorts often have a broad focus and collect(ed) data on various somatic and psychiatric traits as well as environmental factors. Genetic variants have been successfully identified for multiple traits, for example, birth weight, atopic dermatitis, childhood BMI, allergic sensitization, and pubertal growth. Furthermore, the results have shown that genetic factors also partly underlie the association with adult traits. As sample sizes are still increasing, it is expected that future analyses will identify additional variants. This, in combination with the development of innovative statistical methods, will provide detailed insight on the mechanisms underlying the transition from childhood to adult disorders. Both consortia welcome new collaborations. Policies and contact details are available from the corresponding authors of this manuscript and/or the consortium websites.

Published
2019

207. Genome-wide association study of offspring birth weight in 86 577 women identifies five novel loci and highlights maternal genetic effects that are independent of fetal genetics

Author

Beaumont, Robin N., Warrington, Nicole M., Cavadino, Alana, Tyrrell, Jessica, Nodzenski, Michael, Horikoshi, Momoko, Geller, Frank, Myhre, Ronny, Richmond, Rebecca C., Paternoster, Lavinia, Bradfield, Jonathan P., Kreiner-Møller, Eskil, Huikari, Ville, Metrustry, Sarah, Lunetta, Kathryn L., Painter, Jodie N., Hottenga, Jouke-Jan, Allard, Catherine, Barton, Sheila J., Espinosa, Ana, Marsh, Julie A., Potter, Catherine, Zhang, Ge, Ang, Wei, Berry, Diane J., Bouchard, Luigi, Das, Shikta, Hakonarson, Hakon, Heikkinen, Jani, Helgeland, Øyvind, Hocher, Berthold, Hofman, Albert, Inskip, Hazel M., Jones, Samuel E., Kogevinas, Manolis, Lind, Penelope A., Marullo, Letizia, Medland, Sarah E., Murray, Anna, Murray, Jeffrey C., Njølstad, Pa ̊l R., Nohr, Ellen A., Reichetzeder, Christoph, Ring, Susan M., Ruth, Katherine S., Santa-Marina, Loreto, Scholtens, Denise M., Sebert, Sylvain, Sengpiel, Verena, Tuke, Marcus A., Vaudel, Marc, Weedon, Michael N., Willemsen, Gonneke, Wood, Andrew R., Yaghootkar, Hanieh, Muglia, Louis J., Bartels, Meike, Relton, Caroline L., Pennell, Craig E., Chatzi, Leda, Estivill, Xavier, Holloway, John W., Boomsma, Dorret I., Montgomery, Grant W., Murabito, Joanne M., Spector, Tim D., Power, Christine, Ja ̈rvelin, Marjo-Ritta, Bisgaard, Hans, Grant, Struan F.A., Sørensen, Thorkild I.A., Jaddoe, Vincent W., Jacobsson, Bo, Melbye, Mads, McCarthy, Mark I., Hattersley, Andrew T., Hayes, M. Geoffrey, Frayling, Timothy M., Hivert, Marie-France, Felix, Janine F., Hyppo ̈nen, Elina, Lowe, William L. , Jr, Evans, David M., Lawlor, Debbie A., Feenstra, Bjarke, Freathy, Rachel M., Erasmus MC other, Epidemiology, and Pediatrics

Subjects
Biochemistry & Molecular Biology, SUSCEPTIBILITY LOCI, Genotype, BLOOD-PRESSURE, Gestational Age, VARIANTS, Polymorphism, Single Nucleotide, DISEASE, Germinal Center Kinases, GLUCOKINASE GENE, ddc:590, Early Growth Genetics (EGG) Consortium, ddc:570, Birth Weight, Cytochrome P-450 CYP3A, Humans, METAANALYSIS, Alleles, 11 Medical and Health Sciences, Institut für Biochemie und Biologie, Adaptor Proteins, Signal Transducing, Genetics & Heredity, RISK, Science & Technology, Kv1.3 Potassium Channel, Receptor, Melatonin, MT2, HMGA2 Protein, Intracellular Signaling Peptides and Proteins, Genetic Variation, Proteins, GESTATIONAL DIABETES-MELLITUS, 06 Biological Sciences, Protein-Serine-Threonine Kinases, Actins, DNA-Binding Proteins, PREGNANCY, Trans-Activators, Female, Mathematisch-Naturwissenschaftliche Fakultät, Life Sciences & Biomedicine, Transcription Factor 7-Like 2 Protein, FASTING GLUCOSE, Genome-Wide Association Study
Abstract

Genome-wide association studies of birth weight have focused on fetal genetics, whereas relatively little is known about the role of maternal genetic variation. We aimed to identify maternal genetic variants associated with birth weight that could highlight potentially relevant maternal determinants of fetal growth. We meta-analysed data on up to 8.7 million SNPs in up to 86 577 women of European descent from the Early Growth Genetics (EGG) Consortium and the UK Biobank. We used structural equation modelling (SEM) and analyses of mother–child pairs to quantify the separate maternal and fetal genetic effects. Maternal SNPs at 10 loci (MTNR1B, HMGA2, SH2B3, KCNAB1, L3MBTL3, GCK, EBF1, TCF7L2, ACTL9, CYP3A7) were associated with offspring birth weight at P < 5 Â 10 À8 . In SEM analyses, at least 7 of the 10 associations were consistent with effects of the maternal genotype acting via the intrauterine environment, rather than via effects of shared alleles with the fetus. Variants, or correlated proxies, at many of the loci had been previously associated with adult traits, including fasting glucose (MTNR1B, GCK and TCF7L2) and sex hormone levels (CYP3A7), and one (EBF1) with gestational duration. The identified associations indicate that genetic effects on maternal glucose, cytochrome P450 activity and gestational duration, and potentially on maternal blood pressure and immune function, are relevant for fetal growth. Further characterization of these associations in mechanistic and causal analyses will enhance understanding of the potentially modifiable maternal determinants of fetal growth, with the goal of reducing the morbidity and mortality associated with low and high birth weights., Postprints der Universität Potsdam : Mathematisch-Naturwissenschaftliche Reihe, 628

Published
2019
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208. The Early Growth Genetics (EGG) and EArly Genetics and Lifecourse Epidemiology (EAGLE) consortia : design, results and future prospects

Author

Middeldorp, Christel M., Mahajan, Anubha, Horikoshi, Momoko, Robertson, Neil R., Beaumont, Robin N., Bradfield, Jonathan P., Bustamante, Mariona, Cousminer, Diana L., Day, Felix R., De Silva, N. Maneka, Guxens, Monica, Mook-Kanamori, Dennis O., St Pourcain, Beate, Warrington, Nicole M., Adair, Linda S., Ahlqvist, Emma, Ahluwalia, Tarunveer S., Almgren, Peter, Ang, Wei, Atalay, Mustafa, Auvinen, Juha, Bartels, Meike, Beckmann, Jacques S., Bilbao, Jose Ramon, Bond, Tom, Borja, Judith B., Cavadino, Alana, Charoen, Pimphen, Chen, Zhanghua, Coin, Lachlan, Cooper, Cyrus, Curtin, John A., Custovic, Adnan, Das, Shikta, Davies, Gareth E., Dedoussis, George V., Duijts, Liesbeth, Eastwood, Peter R., Eliasen, Anders U., Elliott, Paul, Eriksson, Johan G., Estivill, Xavier, Fadista, Joao, Fedko, Iryna O., Frayling, Timothy M., Gaillard, Romy, Gauderman, W. James, Geller, Frank, Gilliland, Frank, Gilsanz, Vincente, Granell, Raquel, Grarup, Niels, Groop, Leif, Hadley, Dexter, Hakonarson, Hakon, Hansen, Torben, Hartman, Catharina A., Hattersley, Andrew T., Hayes, M. Geoffrey, Hebebrand, Johannes, Heinrich, Joachim, Helgeland, Oyvind, Henders, Anjali K., Henderson, John, Henriksen, Tine B., Hirschhorn, Joel N., Hivert, Marie-France, Hocher, Berthold, Holloway, John W., Holt, Patrick, Hottenga, Jouke-Jan, Hypponen, Elina, Iniguez, Carmen, Johansson, Stefan, Jugessur, Astanand, Kahonen, Mika, Kalkwarf, Heidi J., Kaprio, Jaakko, Karhunen, Ville, Kemp, John P., Kerkhof, Marjan, Koppelman, Gerard H., Korner, Antje, Kotecha, Sailesh, Kreiner-Moller, Eskil, Kulohoma, Benard, Kumar, Ashish, Kutalik, Zoltan, Lahti, Jari, Lappe, Joan M., Larsson, Henrik, Lehtimaki, Terho, Lewin, Alexandra M., Li, Jin, Lichtenstein, Paul, Lindgren, Cecilia M., Lindi, Virpi, Linneberg, Allan, Liu, Xueping, Liu, Jun, Lowe, William L., Jr., Lundstrom, Sebastian, Lyytikainen, Leo-Pekka, Ma, Ronald C. W., Mace, Aurelien, Magi, Reedik, Magnus, Per, Mamun, Abdullah A., Mannikko, Minna, Martin, Nicholas G., Mbarek, Hamdi, McCarthy, Nina S., Medland, Sarah E., Melbye, Mads, Melen, Erik, Mohlke, Karen L., Monnereau, Claire, Morgen, Camilla S., Morris, Andrew P., Murray, Jeffrey C., Myhre, Ronny, Najman, Jackob M., Nivard, Michel G., Nohr, Ellen A., Nolte, Ilja M., Ntalla, Ioanna, O'Reilly, Paul, Oberfield, Sharon E., Oken, Emily, Oldehinkel, Albertine J., Pahkala, Katja, Palviainen, Teemu, Panoutsopoulou, Kalliope, Pedersen, Oluf, Pennell, Craig E., Pershagen, Goran, Pitkanen, Niina, Plomin, Robert, Power, Christine, Prasad, Rashmi B., Prokopenko, Inga, Pulkkinen, Lea, Raikkonen, Katri, Raitakari, Olli T., Reynolds, Rebecca M., Richmond, Rebecca C., Rivadeneira, Fernando, Rodriguez, Alina, Rose, Richard J., Salem, Rany, Santa-Marina, Loreto, Saw, Seang-Mei, Schnurr, Theresia M., Scott, James G., Selzam, Saskia, Shepherd, John A., Simpson, Angela, Skotte, Line, Sleiman, Patrick M. A., Snieder, Harold, Sørensen, Thorkild I. A., Standl, Marie, Steegers, Eric A. P., Strachan, David P., Straker, Leon, Strandberg, Timo, Taylor, Michelle, Teo, Yik-Ying, Thiering, Elisabeth, Torrent, Maties, Tyrrell, Jessica, Uitterlinden, Andre G., van Beijsterveldt, Toos, van der Most, Peter J., van Duijn, Cornelia M., Viikari, Jorma, Vilor-Tejedor, Natalia, Vogelezang, Suzanne, Vonk, Judith M., Vrijkotte, Tanja G. M., Vuoksimaa, Eero, Wang, Carol A., Watkins, William J., Wichmann, H-Erich, Willemsen, Gonneke, Williams, Gail M., Wilson, James F., Wray, Naomi R., Xu, Shujing, Xu, Cheng-Jian, Yaghootkar, Hanieh, Yi, Lu, Zafarmand, Mohammad Hadi, Zeggini, Eleftheria, Zemel, Babette S., Hinney, Anke, Lakka, Timo A., Whitehouse, Andrew J. O., Sunyer, Jordi, Widen, Elisabeth E., Feenstra, Bjarke, Sebert, Sylvain, Jacobsson, Bo, Njolstad, Pal R., Stoltenberg, Camilla, Smith, George Davey, Lawlor, Debbie A., Paternoster, Lavinia, Timpson, Nicholas J., Ong, Ken K., Bisgaard, Hans, Bonnelykke, Klaus, Jaddoe, Vincent W. V., Tiemeier, Henning, Jarvelin, Marjo-Riitta, Evans, David M., Perry, John R. B., Grant, Struan F. A., Boomsma, Dorret I., Freathy, Rachel M., McCarthy, Mark I., Felix, Janine F., Sorensen, Thorkild I. A., Tiemeier, Hen-Ning, Biological Psychology, APH - Mental Health, APH - Personalized Medicine, Amsterdam Neuroscience - Mood, Anxiety, Psychosis, Stress & Sleep, APH - Methodology, APH - Health Behaviors & Chronic Diseases, Pediatrics, Epidemiology, Interdisciplinary Centre Psychopathology and Emotion regulation (ICPE), Groningen Research Institute for Asthma and COPD (GRIAC), Life Course Epidemiology (LCE), Public and occupational health, APH - Aging & Later Life, ARD - Amsterdam Reproduction and Development, ACS - Atherosclerosis & ischemic syndromes, APH - Global Health, Epidemiology and Data Science, Medical Research Council (MRC), Johan Eriksson / Principal Investigator, Department of General Practice and Primary Health Care, Centre of Excellence in Complex Disease Genetics, Institute for Molecular Medicine Finland, University of Helsinki, Department of Public Health, Clinicum, Doctoral Programme in Cognition, Learning, Instruction and Communication, Department of Psychology and Logopedics, Helsinki Collegium for Advanced Studies, Faculty of Medicine, Timo Strandberg / Principal Investigator, Department of Medicine, Elisabeth Ingrid Maria Widen / Principal Investigator, HUS Internal Medicine and Rehabilitation, HUS Abdominal Center, Developmental Psychology Research Group, Genetic Epidemiology, Genomic Discoveries and Clinical Translation, Cognitive and Brain Aging, Middeldorp, Christel M [0000-0002-6218-0428], and Apollo - University of Cambridge Repository

Subjects
Male, Netherlands Twin Register (NTR), embarazo, Epidemiology, C840 Clinical Psychology, LD SCORE REGRESSION, humanos, LOCI, Medizin, adolescente, Genome-wide association study, BLOOD-PRESSURE, Disease, 030204 cardiovascular system & hematology, Cohort Studies, 0302 clinical medicine, Pregnancy, Medicine, 030212 general & internal medicine, Early childhood, C820 Developmental Psychology, estudios de cohortes, Child, C440 Molecular Genetics, Public, Environmental & Occupational Health, Genetics, education.field_of_study, United Kingdom/epidemiology, COMMON VARIANTS, Hälsovetenskaper, adulto, A900 Others in Medicine and Dentistry, 3142 Public health care science, environmental and occupational health, 3. Good health, predicción, ddc, Childhood traits and disorders, Phenotype, Disease/genetics, Research Design, Child, Preschool, fenotipo, Female, ICEP, medicine.symptom, CHILDHOOD OBESITY, Life Sciences & Biomedicine, EArly Genetics Lifecourse Epidemiology (EAGLE) consortium, Adult, medicine.medical_specialty, Adolescent, Birth weight, Population, Consortium, Childhood Traits And Disorders, Longitudinal, enfermedad, Childhood obesity, 1117 Public Health and Health Services, 03 medical and health sciences, SDG 3 - Good Health and Well-being, Health Sciences, Humans, Genetic Predisposition to Disease, GENOME-WIDE ASSOCIATION, education, LONGITUDINAL TWIN, METAANALYSIS, lactante, Science & Technology, Early Growth Genetics (EGG) consortium, business.industry, Infant, Newborn, Infant, predisposición genética a la enfermedad, medicine.disease, BODY-MASS, C800 Psychology, BIRTH-WEIGHT, C420 Human Genetics, United Kingdom, Low birth weight, business, diseño de la investigación, Forecasting
Abstract

The impact of many unfavorable childhood traits or diseases, such as low birth weight and mental disorders, is not limited to childhood and adolescence, as they are also associated with poor outcomes in adulthood, such as cardiovascular disease. Insight into the genetic etiology of childhood and adolescent traits and disorders may therefore provide new perspectives, not only on how to improve wellbeing during childhood, but also how to prevent later adverse outcomes. To achieve the sample sizes required for genetic research, the Early Growth Genetics (EGG) and EArly Genetics and Lifecourse Epidemiology (EAGLE) consortia were established. The majority of the participating cohorts are longitudinal population-based samples, but other cohorts with data on early childhood phenotypes are also involved. Cohorts often have a broad focus and collect(ed) data on various somatic and psychiatric traits as well as environmental factors. Genetic variants have been successfully identified for multiple traits, for example, birth weight, atopic dermatitis, childhood BMI, allergic sensitization, and pubertal growth. Furthermore, the results have shown that genetic factors also partly underlie the association with adult traits. As sample sizes are still increasing, it is expected that future analyses will identify additional variants. This, in combination with the development of innovative statistical methods, will provide detailed insight on the mechanisms underlying the transition from childhood to adult disorders. Both consortia welcome new collaborations. Policies and contact details are available from the corresponding authors of this manuscript and/or the consortium websites., We are grateful to all families and participants who took part in these studies. We also acknowledge and appreciate the unique efforts of the research teams and practitioners contributing to the collection of this wealth of data. C. M. M. is supported by funding from the European Union's Horizon 2020 research and innovation programme under the Marie Sklodowska-Curie grant agreement no. 721567. J. F. F. has received funding from the European Union's Horizon 2020 research and innovation programme under grant agreement No 633595 (DynaHEALTH) and 733206 (LifeCycle). R. M. F. and R. N. B. are supported by Sir Henry Dale Fellowship (Wellcome Trust and Royal Society grant: WT104150). D. L. C. is funded by the American Diabetes Association Grant 1-17-PDF-077. D. O. M-K. was supported by Dutch Science Organization (ZonMW-VENI Grant 916.14.023). N. M. W. is supported by an Australian National Health and Medical Research Council Early Career Fellowship (APP1104818). T. S. A. was partially funded by the Gene-Diet Interactions in Obesity (GENDINOB) project on behalf of GOYA male cohort data management and analyses and acknowledges the same. S. D. was supported by National Institute of Health Research. T. M. F. is supported by the European Research Council grant: 323195 SZ-245 50371-GLUCOSEGENES-FP7-IDEAS-ERC. The Novo Nordisk Foundation Center for Basic Metabolic Research is an independent Research Center at the University of Copenhagen partially funded by an unrestricted donation from the Novo Nordisk Foundation (www.metabol.ku.dk).H.H.is funded by The Children's Hospital of Philadelphia Endowed Chair in Genomic Research. A. T. H. is supported by the Wellcome Trust Senior Investigator Awards (WT098395), National Institute for Health Research (NIHR) Senior Investigator Award (NF-SI-0611-10219). J. Hebebrand received grants from German Research Society, German Ministry of Education and Research. M-F. H. is currently supported by an American Diabetes Association (ADA) Pathway Program Accelerator Early Investigator Award (1-15-ACE-26). S. J. is supported by Helse Vest no. 23929, Bergen Forskningsstiftelse and KG Jebsen Foundation and University of Bergen. J. K. has been supported by the Academy of Finland Research Professor program (grants 265240 & 263278). J. P. K. is funded by a University of Queensland Development Fellowship (UQFEL1718945). H. L. has served as a speaker for Eli-Lilly and Shire and has received research grants from Shire; all outside the submitted work. C. M. L is supported by the Li Ka Shing Foundation, WT-SSI/John Fell funds and by the NIHR Biomedical Research Centre, Oxford, by Widenlife and NIH (5P50HD028138-27). S. E. M. was funded by an NHMRC Senior Reseach Fellowship (APP1103623). K. Panoutsopoulou is funded by a career development fellowship (grant 20308) and by the Wellcome Trust (WT098051). C. P. at UCL Institute of Child Health, with support from the National Institute for Health Research Biomedical Research Centre at Great Ormond Street Hospital for Children NHS Foundation Trust and University College London. I. P. was funded in part by the Wellcome Trust (WT205915), and the European Union's Horizon 2020 research, the European Union FP7-IDEAS-ERC Advanced Grant (GEPIDIAB, ERC-AG -ERC-294785), and innovation programme (DYNAhealth, H2020-PHC-2014-633595). R. C. R. is supported by CRUK (grant number C18281/A19169). J. G. S. is supported by an NHMRC Practitioner Fellowship Grant (APP1105807). J. T.; r is funded by the European Regional Development Fund (ERDF), the European Social Fund (ESF), Convergence Programme for Cornwall and the Isles of Scilly and the Diabetes Research and Wellness Foundation Non-Clinical Fellowship. N. V-T. is funded by a pre-doctoral grant from the Agencia de Gestio d'Ajuts Universitaris i de Recerca (AGAUR) (2015 FI_B 00636), Generalitat de Catalunya. T. G. M. V was supported by ZonMW (TOP 40-00812-98-11010. J. F. W. is supported by the MRC Human Genetics Unit quinquennial programme QTL in Health and Disease. H. Y. is funded by Diabetes UK RD Lawrence fellowship (grant: 17/0005594). M. H. Z was supported by BBMRI-NL (CP2013-50). E. Z. is supported by the Wellcome Trust (098051). B. F. is supported by Novo Nordisk Foundation (12955) and an Oak Foundation Fellowship. S. S. and M-R. J. have received funding from the European Union's Horizon 2020 research and innovation programme [under grant agreement No 633595] for the DynaHEALTH action. P. R. N. was supported by the European Research Council (ERC), University of Bergen, KG Jebsen and Helse Vest. G. D. S. works within the MRC Integrative Epidemiology Unit at the University of Bristol (MC_UU_12013/1). D. A. L was supported by the European Research Council under the European Union's Seventh Framework Programme (FP/2007-2013)/ERC Grant Agreement (Grant number 669545; DevelopObese), US National Institute of Health (grant: R01 DK10324), the UK Medical Research Council (grant: MC_UU_00011/6), Wellcome Trust GWAS grant (WT088806), an NIHR Senior Investigator Award (NF-SI-0611-10196) and the NIHR Biomedical Research Centre at University Hospitals Bristol NHS Foundation Trust and the University of Bristol. L. Paternoster was supported by the UK Medical Research Council Unit grants MC_UU_12013_5. N. J. T. is a Wellcome Trust Investigator (202802/Z/16/Z), is the PI of the Avon Longitudinal Study of Parents and Children (MRC & WT 102215/2/13/2), is supported by the University of Bristol NIHR Biomedical Research Centre (BRC) and works within the CRUK Integrative Cancer Epidemiology Programme (C18281/A19169). V.W.V.J. received an additional grant from the Netherlands Organization for Health Research and Development (NWO, ZonMw-VIDI 016.136.361), a European Research Council Consolidator Grant (ERC-2014-CoG-648916) and funding from the European Union's Horizon 2020 research and innovation programme under grant agreement No 633595 (DynaHEALTH) and 733206 (LifeCycle). D. M. E. is funded by the UK Medical Research Council Unit grant MC_UU_12013_4, Australian Research Council Future Fellowship (FT130101709) and a NHMRC Senior Research Fellowship (GNT1137714). S. F. A. G. is funded by the Daniel B. Burke Endowed Chair for Diabetes Research and R01 HD056465. D. I. B. is supported by Spinozapremie (NWO-56-464-14192) and the Royal Netherlands Academy of Science Professor Award (PAH/6635) to DIB. M. I. M. is a Wellcome Senior Investgator and NIHR Senior Investigator supported by the Wellcome (090532, 098381, 203141), NIHR (NF-SI-0617-10090) and the US National Institute of Health (grant: R01 DK10324), the UK Medical Research Council (grant: MCiabetes UK RD Lawrence fellowship (grant: 17/0005594). M. H. Z was supported by BBMRI-NLNIHR Biomedical Research Centre, Oxford. The views expressed in this article are those of the author(s) and not necessarily those of the NHS, the NIHR, or the Department of Health.

Published
2019

209. Moderate-to-severe asthma in individuals of European ancestry: a genome-wide association study

Author

Hall, Robert, Shrine, Nick, Portelli, Michael A., John, Catherine, Bennett, Neil, Lewis, Jon, Henry, Amanda P., Billington, Charlotte K., Ahmad, Azaz, Packer, Richard J., Shaw, Dominick, Pogson, Zara E.K., Fogarty, Andrew, McKeever, Tricia M., Singapuri, Amisha, Heaney, Liam G., Mansur, Adel H., Chaudhuri, Rekha, Thomson, Neil C., Holloway, John W., Lockett, Gabrielle A., Howarth, Peter H., Djukanovic, Ratko, Hankinson, Jenny, Niven, Robert, Simpson, Angela, Fan Chung, Kian, Sterk, Peter J., Blakey, John D., Adcock, Ian M., Hu, Sile, Guo, Yike, Obeidat, Maen, Sin, Don D., van den Berge, Maarten, Nickle, David C., Tobin, Martin D., Hall, Ian P., Brightling, Christopher E., Wain, Louise V., and Sayers, Ian

Abstract

BackgroundFew genetic studies that focus on moderate-to-severe asthma exist. We aimed to identity novel genetic variants associated with moderate-to-severe asthma, see whether previously identified genetic variants for all types of asthma contribute to moderate-to-severe asthma, and provide novel mechanistic insights using expression analyses in patients with asthma.MethodsIn this genome-wide association study, we used a two-stage case-control design. In stage 1, we genotyped patient-level data from two UK cohorts (the Genetics of Asthma Severity and Phenotypes [GASP] initiative and the Unbiased BIOmarkers in PREDiction of respiratory disease outcomes [U-BIOPRED] project) and used data from the UK Biobank to collect patient-level genomic data for cases and controls of European ancestry in a 1:5 ratio. Cases were defined as having moderate-to-severe asthma if they were taking appropriate medication or had been diagnosed by a doctor. Controls were defined as not having asthma, rhinitis, eczema, allergy, emphysema, or chronic bronchitis as diagnosed by a doctor. For stage 2, an independent cohort of cases and controls (1:5) was selected from the UK Biobank only, with no overlap with stage 1 samples. In stage 1 we undertook a genome-wide association study of moderate-to-severe asthma, and in stage 2 we followed up independent variants that reached the significance threshold of p less than 1 × 10−6 in stage 1. We set genome-wide significance at p less than 5 × 10−8. For novel signals, we investigated their effect on all types of asthma (mild, moderate, and severe). For all signals meeting genome-wide significance, we investigated their effect on gene expression in patients with asthma and controls.FindingsWe included 5135 cases and 25 675 controls for stage 1, and 5414 cases and 21 471 controls for stage 2. We identified 24 genome-wide significant signals of association with moderate-to-severe asthma, including several signals in innate or adaptive immune-response genes. Three novel signals were identified: rs10905284 in GATA3 (coded allele A, odds ratio [OR] 0·90, 95% CI 0·88–0·93; p=1·76 × 10−10), rs11603634 in the MUC5AC region (coded allele G, OR 1·09, 1·06–1·12; p=2·32 × 10−8), and rs560026225 near KIAA1109 (coded allele GATT, OR 1·12, 1·08–1·16; p=3·06 × 10−9). The MUC5AC signal was not associated with asthma when analyses included mild asthma. The rs11603634 G allele was associated with increased expression of MUC5AC mRNA in bronchial epithelial brush samples via proxy SNP rs11602802; (p=2·50 × 10−5) and MUC5AC mRNA was increased in bronchial epithelial samples from patients with severe asthma (in two independent analyses, p=0·039 and p=0·022).InterpretationWe found substantial shared genetic architecture between mild and moderate-to-severe asthma. We also report for the first time genetic variants associated with the risk of developing moderate-to-severe asthma that regulate mucin production. Finally, we identify candidate causal genes in these loci and provide increased insight into this difficult to treat population.

Published
2019

216. Meta-analysis of epigenome-wide association studies in neonates reveals widespread differential DNA methylation associated with birthweight

Author

Küpers, Leanne K, Monnereau, Claire, Sharp, Gemma C, Yousefi, Paul, Salas, Lucas A, Ghantous, Akram, Page, Christian M, Reese, Sarah E, Wilcox, Allen J, Czamara, Darina, Starling, Anne P, Novoloaca, Alexei, Lent, Samantha, Roy, Ritu, Hoyo, Cathrine, Breton, Carrie V, Allard, Catherine, Just, Allan C, Bakulski, Kelly M, Holloway, John W, Everson, Todd M, Xu, Cheng-Jian, Huang, Rae-Chi, van der Plaat, Diana A, Wielscher, Matthias, Merid, Simon Kebede, Ullemar, Vilhelmina, Rezwan, Faisal I, Lahti, Jari, van Dongen, Jenny, Langie, Sabine A S, Richardson, Tom G, Magnus, Maria C, Nohr, Ellen A, Xu, Zongli, Duijts, Liesbeth, Zhao, Shanshan, Zhang, Weiming, Plusquin, Michelle, DeMeo, Dawn L, Solomon, Olivia, Heimovaara, Joosje H, Jima, Dereje D, Gao, Lu, Bustamante, Mariona, Perron, Patrice, Wright, Robert O, Hertz-Picciotto, Irva, Zhang, Hongmei, Gehring, Ulrike, Küpers, Leanne K, Monnereau, Claire, Sharp, Gemma C, Yousefi, Paul, Salas, Lucas A, Ghantous, Akram, Page, Christian M, Reese, Sarah E, Wilcox, Allen J, Czamara, Darina, Starling, Anne P, Novoloaca, Alexei, Lent, Samantha, Roy, Ritu, Hoyo, Cathrine, Breton, Carrie V, Allard, Catherine, Just, Allan C, Bakulski, Kelly M, Holloway, John W, Everson, Todd M, Xu, Cheng-Jian, Huang, Rae-Chi, van der Plaat, Diana A, Wielscher, Matthias, Merid, Simon Kebede, Ullemar, Vilhelmina, Rezwan, Faisal I, Lahti, Jari, van Dongen, Jenny, Langie, Sabine A S, Richardson, Tom G, Magnus, Maria C, Nohr, Ellen A, Xu, Zongli, Duijts, Liesbeth, Zhao, Shanshan, Zhang, Weiming, Plusquin, Michelle, DeMeo, Dawn L, Solomon, Olivia, Heimovaara, Joosje H, Jima, Dereje D, Gao, Lu, Bustamante, Mariona, Perron, Patrice, Wright, Robert O, Hertz-Picciotto, Irva, Zhang, Hongmei, and Gehring, Ulrike

Abstract

Birthweight is associated with health outcomes across the life course, DNA methylation may be an underlying mechanism. In this meta-analysis of epigenome-wide association studies of 8,825 neonates from 24 birth cohorts in the Pregnancy And Childhood Epigenetics Consortium, we find that DNA methylation in neonatal blood is associated with birthweight at 914 sites, with a difference in birthweight ranging from -183 to 178 grams per 10% increase in methylation (PBonferroni < 1.06 x 10-7). In additional analyses in 7,278 participants, <1.3% of birthweight-associated differential methylation is also observed in childhood and adolescence, but not adulthood. Birthweight-related CpGs overlap with some Bonferroni-significant CpGs that were previously reported to be related to maternal smoking (55/914, p = 6.12 x 10-74) and BMI in pregnancy (3/914, p = 1.13x10-3), but not with those related to folate levels in pregnancy. Whether the associations that we observe are causal or explained by confounding or fetal growth influencing DNA methylation (i.e. reverse causality) requires further research.

Published
2019

217. Epigenome-wide association study of lung function level and its change

Author

Imboden, Medea, Wielscher, Matthias, Rezwan, Faisal I, Amaral, André F S, Schaffner, Emmanuel, Jeong, Ayoung, Beckmeyer-Borowko, Anna, Harris, Sarah E, Starr, John M, Deary, Ian J, Flexeder, Claudia, Waldenberger, Melanie, Peters, Annette, Schulz, Holger, Chen, Su, Sunny, Shadia Khan, Karmaus, Wilfried J J, Jiang, Yu, Erhart, Gertraud, Kronenberg, Florian, Arathimos, Ryan, Sharp, Gemma C, Henderson, Alexander John, Fu, Yu, Piirilä, Päivi, Pietiläinen, Kirsi H, Ollikainen, Miina, Johansson, Åsa, Gyllensten, Ulf B., de Vries, Maaike, van der Plaat, Diana A, de Jong, Kim, Boezen, H Marike, Hall, Ian P, Tobin, Martin D, Jarvelin, Marjo-Riitta, Holloway, John W, Jarvis, Deborah, Probst-Hensch, Nicole M, Imboden, Medea, Wielscher, Matthias, Rezwan, Faisal I, Amaral, André F S, Schaffner, Emmanuel, Jeong, Ayoung, Beckmeyer-Borowko, Anna, Harris, Sarah E, Starr, John M, Deary, Ian J, Flexeder, Claudia, Waldenberger, Melanie, Peters, Annette, Schulz, Holger, Chen, Su, Sunny, Shadia Khan, Karmaus, Wilfried J J, Jiang, Yu, Erhart, Gertraud, Kronenberg, Florian, Arathimos, Ryan, Sharp, Gemma C, Henderson, Alexander John, Fu, Yu, Piirilä, Päivi, Pietiläinen, Kirsi H, Ollikainen, Miina, Johansson, Åsa, Gyllensten, Ulf B., de Vries, Maaike, van der Plaat, Diana A, de Jong, Kim, Boezen, H Marike, Hall, Ian P, Tobin, Martin D, Jarvelin, Marjo-Riitta, Holloway, John W, Jarvis, Deborah, and Probst-Hensch, Nicole M

Abstract

Previous reports link differential DNA methylation (DNAme) to environmental exposures that are associated with lung function. Direct evidence on lung function DNAme is, however, limited. We undertook an agnostic epigenome-wide association study (EWAS) on pre-bronchodilation lung function and its change in adults.In a discovery-replication EWAS design, DNAme in blood and spirometry were measured twice, 6-15 years apart, in the same participants of three adult population-based discovery cohorts (n=2043). Associated DNAme markers (p<5×10-7) were tested in seven replication cohorts (adult: n=3327; childhood: n=420). Technical bias-adjusted residuals of a regression of the normalised absolute β-values on control probe-derived principle components were regressed on level and change of forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC) and their ratio (FEV1/FVC) in the covariate-adjusted discovery EWAS. Inverse-variance-weighted meta-analyses were performed on results from discovery and replication samples in all participants and never-smokers.EWAS signals were enriched for smoking-related DNAme. We replicated 57 lung function DNAme markers in adult, but not childhood samples, all previously associated with smoking. Markers not previously associated with smoking failed replication. cg05575921 (AHRR (aryl hydrocarbon receptor repressor)) showed the statistically most significant association with cross-sectional lung function (FEV1/FVC: pdiscovery=3.96×10-21 and pcombined=7.22×10-50). A score combining 10 DNAme markers previously reported to mediate the effect of smoking on lung function was associated with lung function (FEV1/FVC: p=2.65×10-20).Our results reveal that lung function-associated methylation signals in adults are predominantly smoking related, and possibly of clinical utility in identifying poor lung function and accelerated decline. Larger studies with more repeat time-points are needed to identify lung function DNAme in never-smokers and i

Published
2019
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218. A three-generation study on the association of tobacco smoking with asthma

Author

Accordini, Simone, Calciano, Lucia, Johannessen, Ane, Portas, Laura, Benediktsdóttir, Bryndis, Bertelsen, Randi Jacobsen, Bråbäck, Lennart, Carsin, Anne-Elie, Dharmage, Shyamali C, Dratva, Julia, Forsberg, Bertil, Gomez Real, Francisco, Heinrich, Joachim, Holloway, John W, Holm, Mathias, Janson, Christer, Jögi, Rain, Leynaert, Bénédicte, Malinovschi, Andrei, Marcon, Alessandro, Martínez-Moratalla Rovira, Jesús, Raherison, Chantal, Sánchez-Ramos, José Luis, Schlünssen, Vivi, Bono, Roberto, Corsico, Angelo G, Demoly, Pascal, Dorado Arenas, Sandra, Nowak, Dennis, Pin, Isabelle, Weyler, Joost, Jarvis, Deborah, Svanes, Cecilie, Accordini, Simone, Calciano, Lucia, Johannessen, Ane, Portas, Laura, Benediktsdóttir, Bryndis, Bertelsen, Randi Jacobsen, Bråbäck, Lennart, Carsin, Anne-Elie, Dharmage, Shyamali C, Dratva, Julia, Forsberg, Bertil, Gomez Real, Francisco, Heinrich, Joachim, Holloway, John W, Holm, Mathias, Janson, Christer, Jögi, Rain, Leynaert, Bénédicte, Malinovschi, Andrei, Marcon, Alessandro, Martínez-Moratalla Rovira, Jesús, Raherison, Chantal, Sánchez-Ramos, José Luis, Schlünssen, Vivi, Bono, Roberto, Corsico, Angelo G, Demoly, Pascal, Dorado Arenas, Sandra, Nowak, Dennis, Pin, Isabelle, Weyler, Joost, Jarvis, Deborah, and Svanes, Cecilie

Abstract

Background: Mothers’ smoking during pregnancy increases asthma risk in their offspring. There is some evidence that grandmothers’ smoking may have a similar effect, and biological plausibility that fathers’ smoking during adolescence may influence offspring’s health through transmittable epigenetic changes in sperm precursor cells. We evaluated the three-generation associations of tobacco smoking with asthma. Methods: Between 2010 and 2013, at the European Community Respiratory Health Survey III clinical interview, 2233 mothers and 1964 fathers from 26 centres reported whether their offspring (aged ≤51 years) had ever had asthma and whether it had coexisted with nasal allergies or not. Mothers and fathers also provided information on their parents’ (grandparents) and their own asthma, education and smoking history. Multilevel mediation models within a multicentre three-generation framework were fitted separately within the maternal (4666 offspring) and paternal (4192 offspring) lines. Results: Fathers’ smoking before they were 15 [relative risk ratio (RRR) = 1.43, 95% confidence interval (CI): 1.01–2.01] and mothers’ smoking during pregnancy (RRR = 1.27, 95% CI: 1.01-1.59) were associated with asthma without nasal allergies in their offspring. Grandmothers’ smoking during pregnancy was associated with asthma in their daughters [odds ratio (OR) = 1.55, 95% CI: 1.17-2.06] and with asthma with nasal allergies in their grandchildren within the maternal line (RRR = 1.25, 95% CI: 1.02-1.55). Conclusions: Fathers’ smoking during early adolescence and grandmothers’ and mothers’ smoking during pregnancy may independently increase asthma risk in offspring. Thus, risk factors for asthma should be sought in both parents and before conception.

Published
2019

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

Author

Warrington, Nicole M, 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, EGG Consortium, 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, Warrington, Nicole M, 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, EGG Consortium, 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, and Fonvig, Cilius E

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

220. Moderate-to-severe asthma in individuals of European ancestry: a genome-wide association study

Author

Shrine, Nick, Portelli, Michael A., John, Catherine, Soler Artigas, Maria, Bennett, Neil, Hall, Robert, Lewis, Jon, Henry, Amanda P., Billington, Charlotte K., Ahmad, Azaz, Packer, Richard J., Shaw, Dominick, Pogson, Zara E.K., Fogarty, Andrew, McKeever, Tricia M., Singapuri, Amisha, Heaney, Liam G., Mansur, Adel H., Chaudhuri, Rekha, Thomson, Neil C., Holloway, John W., Lockett, Gabrielle A., Howarth, Peter H., Djukanovic, Ratko, Hankinson, Jenny, Niven, Robert, Simpson, Angela, Chung, Kian Fan, Sterk, P.eter J., Blakey, John D., Adcock, Ian M., Hu, Sile, Guo, Yike, Obeidat, Maen, Sin, Don D., van den Berge, Maarten, Nickle, David C., Bossé, Yohan, Tobin, Martin D., Hall, Ian P., Brightling, Christopher E., Wain, Louise V., Sayers, Ian, Shrine, Nick, Portelli, Michael A., John, Catherine, Soler Artigas, Maria, Bennett, Neil, Hall, Robert, Lewis, Jon, Henry, Amanda P., Billington, Charlotte K., Ahmad, Azaz, Packer, Richard J., Shaw, Dominick, Pogson, Zara E.K., Fogarty, Andrew, McKeever, Tricia M., Singapuri, Amisha, Heaney, Liam G., Mansur, Adel H., Chaudhuri, Rekha, Thomson, Neil C., Holloway, John W., Lockett, Gabrielle A., Howarth, Peter H., Djukanovic, Ratko, Hankinson, Jenny, Niven, Robert, Simpson, Angela, Chung, Kian Fan, Sterk, P.eter J., Blakey, John D., Adcock, Ian M., Hu, Sile, Guo, Yike, Obeidat, Maen, Sin, Don D., van den Berge, Maarten, Nickle, David C., Bossé, Yohan, Tobin, Martin D., Hall, Ian P., Brightling, Christopher E., Wain, Louise V., and Sayers, Ian

Abstract

Background: Few genetic studies that focus on moderate-to-severe asthma exist. We aimed to identity novel genetic variants associated with moderate-to-severe asthma, see whether previously identified genetic variants for all types of asthma contribute to moderate-to-severe asthma, and provide novel mechanistic insights using expression analyses in patients with asthma. Methods: In this genome-wide association study, we used a two-stage case-control design. In stage 1, we genotyped patient-level data from two UK cohorts (the Genetics of Asthma Severity and Phenotypes [GASP] initiative and the Unbiased BIOmarkers in PREDiction of respiratory disease outcomes [U-BIOPRED] project) and used data from the UK Biobank to collect patient-level genomic data for cases and controls of European ancestry in a 1:5 ratio. Cases were defined as having moderate-to-severe asthma if they were taking appropriate medication or had been diagnosed by a doctor. Controls were defined as not having asthma, rhinitis, eczema, allergy, emphysema, or chronic bronchitis as diagnosed by a doctor. For stage 2, an independent cohort of cases and controls (1:5) was selected from the UK Biobank only, with no overlap with stage 1 samples. In stage 1 we undertook a genome-wide association study of moderate-to-severe asthma, and in stage 2 we followed up independent variants that reached the significance threshold of p less than 1 × 10 −6 in stage 1. We set genome-wide significance at p less than 5 × 10 −8 . For novel signals, we investigated their effect on all types of asthma (mild, moderate, and severe). For all signals meeting genome-wide significance, we investigated their effect on gene expression in patients with asthma and controls. Findings: We included 5135 cases and 25 675 controls for stage 1, and 5414 cases and 21 471 controls for stage 2. We identified 24 genome-wide significant signals of association with moderate-to-severe asthma, including several signals in innate or adaptive immune-resp

Published
2019

221. Hypertensive Disorders of Pregnancy and DNA Methylation in Newborns Findings From the Pregnancy and Childhood Epigenetics Consortium

Author

Kazmi, Nabila, Sharp, Gemma C., Reese, Sarah E., Vehmeijer, Florianne O., Lahti, Jari, Page, Christian M., Zhang, Weiming, Rifas-Shiman, Sheryl L., Rezwan, Faisal I., Simpkin, Andrew J., Burrows, Kimberley, Richardson, Tom G., Ferreira, Diana L. Santos, Fraser, Abigail, Harmon, Quaker E., Zhao, Shanshan, Jaddoe, Vincent W. V., Czamara, Darina, Binder, Elisabeth B., Magnus, Maria C., Haberg, Siri E., Nystad, Wenche, Nohr, Ellen A., Starling, Anne P., Kechris, Katerina J., Yang, Ivana V., DeMeo, Dawn L., Litonjua, Augusto A., Baccarelli, Andrea, Oken, Emily, Holloway, John W., Karmaus, Wilfried, Arshad, Syed H., Dabelea, Dana, Sorensen, Thorkild I. A., Laivuori, Hannele, Raikkonen, Katri, Felix, Janine F., London, Stephanie J., Hivert, Marie-France, Gaunt, Tom R., Lawlor, Debbie A., Relton, Caroline L., Kazmi, Nabila, Sharp, Gemma C., Reese, Sarah E., Vehmeijer, Florianne O., Lahti, Jari, Page, Christian M., Zhang, Weiming, Rifas-Shiman, Sheryl L., Rezwan, Faisal I., Simpkin, Andrew J., Burrows, Kimberley, Richardson, Tom G., Ferreira, Diana L. Santos, Fraser, Abigail, Harmon, Quaker E., Zhao, Shanshan, Jaddoe, Vincent W. V., Czamara, Darina, Binder, Elisabeth B., Magnus, Maria C., Haberg, Siri E., Nystad, Wenche, Nohr, Ellen A., Starling, Anne P., Kechris, Katerina J., Yang, Ivana V., DeMeo, Dawn L., Litonjua, Augusto A., Baccarelli, Andrea, Oken, Emily, Holloway, John W., Karmaus, Wilfried, Arshad, Syed H., Dabelea, Dana, Sorensen, Thorkild I. A., Laivuori, Hannele, Raikkonen, Katri, Felix, Janine F., London, Stephanie J., Hivert, Marie-France, Gaunt, Tom R., Lawlor, Debbie A., and Relton, Caroline L.

Published
2019

222. Meta-analysis of epigenome-wide association studies in neonates reveals widespread differential DNA methylation associated with birthweight

Author

Kupers, Leanne K., Monnereau, Claire, Sharp, Gemma C., Yousefi, Paul, Salas, Lucas A., Ghantous, Akram, Page, Christian M., Reese, Sarah E., Wilcox, Allen J., Czamara, Darina, Starling, Anne P., Novoloaca, Alexei, Lent, Samantha, Roy, Ritu, Hoyo, Cathrine, Breton, Carrie, V, Allard, Catherine, Just, Allan C., Bakulski, Kelly M., Holloway, John W., Everson, Todd M., Xu, Cheng-Jian, Huang, Rae-Chi, van der Plaat, Diana A., Wielscher, Matthias, Merid, Simon Kebede, Ullemar, Vilhelmina, Rezwan, Faisal, I, Lahti, Jari, van Dongen, Jenny, Langie, Sabine A. S., Richardson, Tom G., Magnus, Maria C., Nohr, Ellen A., Xu, Zongli, Duijts, Liesbeth, Zhao, Shanshan, Zhang, Weiming, Plusquin, Michelle, DeMeo, Dawn L., Solomon, Olivia, Heimovaara, Joosje H., Jima, Dereje D., Gao, Lu, Bustamante, Mariona, Perron, Patrice, Wright, Robert O., Hertz-Picciotto, Irva, Zhang, Hongmei, Karagas, Margaret R., Gehring, Ulrike, Marsit, Carmen J., Beilin, Lawrence J., Vonk, Judith M., Jarvelin, Marjo-Riitta, Bergstrom, Anna, Ortqvist, Anne K., Ewart, Susan, Villa, Pia M., Moore, Sophie E., Willemsen, Gonneke, Standaert, Arnout R. L., Haberg, Siri E., Sørensen, Thorkild I. A., Taylor, Jack A., Raikkonen, Katri, Yang, Ivana, V, Kechris, Katerina, Nawrot, Tim S., Silver, Matt J., Gong, Yun Yun, Richiardi, Lorenzo, Kogevinas, Manolis, Litonjua, Augusto A., Eskenazi, Brenda, Huen, Karen, Mbarek, Hamdi, Maguire, Rachel L., Dwyer, Terence, Vrijheid, Martine, Bouchard, Luigi, Baccarelli, Andrea A., Croen, Lisa A., Karmaus, Wilfried, Anderson, Denise, de Vries, Maaike, Sebert, Sylvain, Kere, Juha, Karlsson, Robert, Arshad, Syed Hasan, Hamalainen, Esa, Routledge, Michael N., Boomsma, Dorret, I, Feinberg, Andrew P., Newschaffer, Craig J., Govarts, Eva, Moisse, Matthieu, Fallin, M. Daniele, Melen, Erik, Prentice, Andrew M., Kajantie, Eero, Almqvist, Catarina, Oken, Emily, Dabelea, Dana, Boezen, H. Marike, Melton, Phillip E., Wright, Rosalind J., Koppelman, Gerard H., Trevisi, Letizia, Hivert, Marie-France, Sunyer, Jordi, Munthe-Kaas, Monica C., Murphy, Susan K., Corpeleijn, Eva, Wiemels, Joseph, Holland, Nina, Herceg, Zdenko, Binder, Elisabeth B., Smith, George Davey, Jaddoe, Vincent W. V., Lie, Rolv T., Nystad, Wenche, London, Stephanie J., Lawlor, Debbie A., Relton, Caroline L., Snieder, Harold, Felix, Janine F., Kupers, Leanne K., Monnereau, Claire, Sharp, Gemma C., Yousefi, Paul, Salas, Lucas A., Ghantous, Akram, Page, Christian M., Reese, Sarah E., Wilcox, Allen J., Czamara, Darina, Starling, Anne P., Novoloaca, Alexei, Lent, Samantha, Roy, Ritu, Hoyo, Cathrine, Breton, Carrie, V, Allard, Catherine, Just, Allan C., Bakulski, Kelly M., Holloway, John W., Everson, Todd M., Xu, Cheng-Jian, Huang, Rae-Chi, van der Plaat, Diana A., Wielscher, Matthias, Merid, Simon Kebede, Ullemar, Vilhelmina, Rezwan, Faisal, I, Lahti, Jari, van Dongen, Jenny, Langie, Sabine A. S., Richardson, Tom G., Magnus, Maria C., Nohr, Ellen A., Xu, Zongli, Duijts, Liesbeth, Zhao, Shanshan, Zhang, Weiming, Plusquin, Michelle, DeMeo, Dawn L., Solomon, Olivia, Heimovaara, Joosje H., Jima, Dereje D., Gao, Lu, Bustamante, Mariona, Perron, Patrice, Wright, Robert O., Hertz-Picciotto, Irva, Zhang, Hongmei, Karagas, Margaret R., Gehring, Ulrike, Marsit, Carmen J., Beilin, Lawrence J., Vonk, Judith M., Jarvelin, Marjo-Riitta, Bergstrom, Anna, Ortqvist, Anne K., Ewart, Susan, Villa, Pia M., Moore, Sophie E., Willemsen, Gonneke, Standaert, Arnout R. L., Haberg, Siri E., Sørensen, Thorkild I. A., Taylor, Jack A., Raikkonen, Katri, Yang, Ivana, V, Kechris, Katerina, Nawrot, Tim S., Silver, Matt J., Gong, Yun Yun, Richiardi, Lorenzo, Kogevinas, Manolis, Litonjua, Augusto A., Eskenazi, Brenda, Huen, Karen, Mbarek, Hamdi, Maguire, Rachel L., Dwyer, Terence, Vrijheid, Martine, Bouchard, Luigi, Baccarelli, Andrea A., Croen, Lisa A., Karmaus, Wilfried, Anderson, Denise, de Vries, Maaike, Sebert, Sylvain, Kere, Juha, Karlsson, Robert, Arshad, Syed Hasan, Hamalainen, Esa, Routledge, Michael N., Boomsma, Dorret, I, Feinberg, Andrew P., Newschaffer, Craig J., Govarts, Eva, Moisse, Matthieu, Fallin, M. Daniele, Melen, Erik, Prentice, Andrew M., Kajantie, Eero, Almqvist, Catarina, Oken, Emily, Dabelea, Dana, Boezen, H. Marike, Melton, Phillip E., Wright, Rosalind J., Koppelman, Gerard H., Trevisi, Letizia, Hivert, Marie-France, Sunyer, Jordi, Munthe-Kaas, Monica C., Murphy, Susan K., Corpeleijn, Eva, Wiemels, Joseph, Holland, Nina, Herceg, Zdenko, Binder, Elisabeth B., Smith, George Davey, Jaddoe, Vincent W. V., Lie, Rolv T., Nystad, Wenche, London, Stephanie J., Lawlor, Debbie A., Relton, Caroline L., Snieder, Harold, and Felix, Janine F.

Published
2019

223. The Early Growth Genetics (EGG) and EArly Genetics and Lifecourse Epidemiology (EAGLE) consortia:design, results and future prospects

Author

Middeldorp, Christel M., Mahajan, Anubha, Horikoshi, Momoko, Robertson, Neil R., Beaumont, Robin N., Bradfield, Jonathan P., Bustamante, Mariona, Cousminer, Diana L., Day, Felix R., De Silva, N. Maneka, Guxens, Monica, Mook-Kanamori, Dennis O., St Pourcain, Beate, Warrington, Nicole M., Adair, Linda S., Ahlqvist, Emma, Ahluwalia, Tarunveer S., Almgren, Peter, Ang, Wei, Atalay, Mustafa, Auvinen, Juha, Bartels, Meike, Beckmann, Jacques S., Bilbao, Jose Ramon, Bond, Tom, Borja, Judith B., Cavadino, Alana, Charoen, Pimphen, Chen, Zhanghua, Coin, Lachlan, Cooper, Cyrus, Curtin, John A., Custovic, Adnan, Das, Shikta, Davies, Gareth E., Dedoussis, George V., Duijts, Liesbeth, Eastwood, Peter R., Eliasen, Anders U., Elliott, Paul, Eriksson, Johan G., Estivill, Xavier, Fadista, Joao, Fedko, Iryna O., Frayling, Timothy M., Gaillard, Romy, Gauderman, W. James, Geller, Frank, Gilliland, Frank, Gilsanz, Vincente, Granell, Raquel, Grarup, Niels, Groop, Leif, Hadley, Dexter, Hakonarson, Hakon, Hansen, Torben, Hartman, Catharina A., Hattersley, Andrew T., Hayes, M. Geoffrey, Hebebrand, Johannes, Heinrich, Joachim, Helgeland, Oyvind, Henders, Anjali K., Henderson, John, Henriksen, Tine B., Hirschhorn, Joel N., Hivert, Marie-France, Hocher, Berthold, Holloway, John W., Holt, Patrick, Hottenga, Jouke-Jan, Hypponen, Elina, Iniguez, Carmen, Johansson, Stefan, Jugessur, Astanand, Kahonen, Mika, Kalkwarf, Heidi J., Kaprio, Jaakko, Karhunen, Ville, Kemp, John P., Kerkhof, Marjan, Koppelman, Gerard H., Korner, Antje, Kotecha, Sailesh, Kreiner-Moller, Eskil, Kulohoma, Benard, Kumar, Ashish, Kutalik, Zoltan, Lahti, Jari, Lappe, Joan M., Larsson, Henrik, Lehtimaki, Terho, Lewin, Alexandra M., Li, Jin, Lichtenstein, Paul, Lindgren, Cecilia M., Lindi, Virpi, Linneberg, Allan, Liu, Xueping, Liu, Jun, Lowe, William L., Jr., Lundstrom, Sebastian, Lyytikainen, Leo-Pekka, Ma, Ronald C. W., Mace, Aurelien, Magi, Reedik, Magnus, Per, Mamun, Abdullah A., Mannikko, Minna, Martin, Nicholas G., Mbarek, Hamdi, McCarthy, Nina S., Medland, Sarah E., Melbye, Mads, Melen, Erik, Mohlke, Karen L., Monnereau, Claire, Morgen, Camilla S., Morris, Andrew P., Murray, Jeffrey C., Myhre, Ronny, Najman, Jackob M., Nivard, Michel G., Nohr, Ellen A., Nolte, Ilja M., Ntalla, Ioanna, O'Reilly, Paul, Oberfield, Sharon E., Oken, Emily, Oldehinkel, Albertine J., Pahkala, Katja, Palviainen, Teemu, Panoutsopoulou, Kalliope, Pedersen, Oluf, Pennell, Craig E., Pershagen, Goran, Pitkanen, Niina, Plomin, Robert, Power, Christine, Prasad, Rashmi B., Prokopenko, Inga, Pulkkinen, Lea, Raikkonen, Katri, Raitakari, Olli T., Reynolds, Rebecca M., Richmond, Rebecca C., Rivadeneira, Fernando, Rodriguez, Alina, Rose, Richard J., Salem, Rany, Santa-Marina, Loreto, Saw, Seang-Mei, Schnurr, Theresia M., Scott, James G., Selzam, Saskia, Shepherd, John A., Simpson, Angela, Skotte, Line, Sleiman, Patrick M. A., Snieder, Harold, Sørensen, Thorkild I. A., Standl, Marie, Steegers, Eric A. P., Strachan, David P., Straker, Leon, Strandberg, Timo, Taylor, Michelle, Teo, Yik-Ying, Thiering, Elisabeth, Torrent, Maties, Tyrrell, Jessica, Uitterlinden, Andre G., van Beijsterveldt, Toos, van der Most, Peter J., van Duijn, Cornelia M., Viikari, Jorma, Vilor-Tejedor, Natalia, Vogelezang, Suzanne, Vonk, Judith M., Vrijkotte, Tanja G. M., Vuoksimaa, Eero, Wang, Carol A., Watkins, William J., Wichmann, H-Erich, Willemsen, Gonneke, Williams, Gail M., Wilson, James F., Wray, Naomi R., Xu, Shujing, Xu, Cheng-Jian, Yaghootkar, Hanieh, Yi, Lu, Zafarmand, Mohammad Hadi, Zeggini, Eleftheria, Zemel, Babette S., Hinney, Anke, Lakka, Timo A., Whitehouse, Andrew J. O., Sunyer, Jordi, Widen, Elisabeth E., Feenstra, Bjarke, Sebert, Sylvain, Jacobsson, Bo, Njolstad, Pal R., Stoltenberg, Camilla, Smith, George Davey, Lawlor, Debbie A., Paternoster, Lavinia, Timpson, Nicholas J., Ong, Ken K., Bisgaard, Hans, Bonnelykke, Klaus, Jaddoe, Vincent W. V., Tiemeier, Henning, Jarvelin, Marjo-Riitta, Evans, David M., Perry, John R. B., Grant, Struan F. A., Boomsma, Dorret I., Freathy, Rachel M., McCarthy, Mark I., Felix, Janine F., Sorensen, Thorkild I. A., Tiemeier, Hen-Ning, Middeldorp, Christel M., Mahajan, Anubha, Horikoshi, Momoko, Robertson, Neil R., Beaumont, Robin N., Bradfield, Jonathan P., Bustamante, Mariona, Cousminer, Diana L., Day, Felix R., De Silva, N. Maneka, Guxens, Monica, Mook-Kanamori, Dennis O., St Pourcain, Beate, Warrington, Nicole M., Adair, Linda S., Ahlqvist, Emma, Ahluwalia, Tarunveer S., Almgren, Peter, Ang, Wei, Atalay, Mustafa, Auvinen, Juha, Bartels, Meike, Beckmann, Jacques S., Bilbao, Jose Ramon, Bond, Tom, Borja, Judith B., Cavadino, Alana, Charoen, Pimphen, Chen, Zhanghua, Coin, Lachlan, Cooper, Cyrus, Curtin, John A., Custovic, Adnan, Das, Shikta, Davies, Gareth E., Dedoussis, George V., Duijts, Liesbeth, Eastwood, Peter R., Eliasen, Anders U., Elliott, Paul, Eriksson, Johan G., Estivill, Xavier, Fadista, Joao, Fedko, Iryna O., Frayling, Timothy M., Gaillard, Romy, Gauderman, W. James, Geller, Frank, Gilliland, Frank, Gilsanz, Vincente, Granell, Raquel, Grarup, Niels, Groop, Leif, Hadley, Dexter, Hakonarson, Hakon, Hansen, Torben, Hartman, Catharina A., Hattersley, Andrew T., Hayes, M. Geoffrey, Hebebrand, Johannes, Heinrich, Joachim, Helgeland, Oyvind, Henders, Anjali K., Henderson, John, Henriksen, Tine B., Hirschhorn, Joel N., Hivert, Marie-France, Hocher, Berthold, Holloway, John W., Holt, Patrick, Hottenga, Jouke-Jan, Hypponen, Elina, Iniguez, Carmen, Johansson, Stefan, Jugessur, Astanand, Kahonen, Mika, Kalkwarf, Heidi J., Kaprio, Jaakko, Karhunen, Ville, Kemp, John P., Kerkhof, Marjan, Koppelman, Gerard H., Korner, Antje, Kotecha, Sailesh, Kreiner-Moller, Eskil, Kulohoma, Benard, Kumar, Ashish, Kutalik, Zoltan, Lahti, Jari, Lappe, Joan M., Larsson, Henrik, Lehtimaki, Terho, Lewin, Alexandra M., Li, Jin, Lichtenstein, Paul, Lindgren, Cecilia M., Lindi, Virpi, Linneberg, Allan, Liu, Xueping, Liu, Jun, Lowe, William L., Jr., Lundstrom, Sebastian, Lyytikainen, Leo-Pekka, Ma, Ronald C. W., Mace, Aurelien, Magi, Reedik, Magnus, Per, Mamun, Abdullah A., Mannikko, Minna, Martin, Nicholas G., Mbarek, Hamdi, McCarthy, Nina S., Medland, Sarah E., Melbye, Mads, Melen, Erik, Mohlke, Karen L., Monnereau, Claire, Morgen, Camilla S., Morris, Andrew P., Murray, Jeffrey C., Myhre, Ronny, Najman, Jackob M., Nivard, Michel G., Nohr, Ellen A., Nolte, Ilja M., Ntalla, Ioanna, O'Reilly, Paul, Oberfield, Sharon E., Oken, Emily, Oldehinkel, Albertine J., Pahkala, Katja, Palviainen, Teemu, Panoutsopoulou, Kalliope, Pedersen, Oluf, Pennell, Craig E., Pershagen, Goran, Pitkanen, Niina, Plomin, Robert, Power, Christine, Prasad, Rashmi B., Prokopenko, Inga, Pulkkinen, Lea, Raikkonen, Katri, Raitakari, Olli T., Reynolds, Rebecca M., Richmond, Rebecca C., Rivadeneira, Fernando, Rodriguez, Alina, Rose, Richard J., Salem, Rany, Santa-Marina, Loreto, Saw, Seang-Mei, Schnurr, Theresia M., Scott, James G., Selzam, Saskia, Shepherd, John A., Simpson, Angela, Skotte, Line, Sleiman, Patrick M. A., Snieder, Harold, Sørensen, Thorkild I. A., Standl, Marie, Steegers, Eric A. P., Strachan, David P., Straker, Leon, Strandberg, Timo, Taylor, Michelle, Teo, Yik-Ying, Thiering, Elisabeth, Torrent, Maties, Tyrrell, Jessica, Uitterlinden, Andre G., van Beijsterveldt, Toos, van der Most, Peter J., van Duijn, Cornelia M., Viikari, Jorma, Vilor-Tejedor, Natalia, Vogelezang, Suzanne, Vonk, Judith M., Vrijkotte, Tanja G. M., Vuoksimaa, Eero, Wang, Carol A., Watkins, William J., Wichmann, H-Erich, Willemsen, Gonneke, Williams, Gail M., Wilson, James F., Wray, Naomi R., Xu, Shujing, Xu, Cheng-Jian, Yaghootkar, Hanieh, Yi, Lu, Zafarmand, Mohammad Hadi, Zeggini, Eleftheria, Zemel, Babette S., Hinney, Anke, Lakka, Timo A., Whitehouse, Andrew J. O., Sunyer, Jordi, Widen, Elisabeth E., Feenstra, Bjarke, Sebert, Sylvain, Jacobsson, Bo, Njolstad, Pal R., Stoltenberg, Camilla, Smith, George Davey, Lawlor, Debbie A., Paternoster, Lavinia, Timpson, Nicholas J., Ong, Ken K., Bisgaard, Hans, Bonnelykke, Klaus, Jaddoe, Vincent W. V., Tiemeier, Henning, Jarvelin, Marjo-Riitta, Evans, David M., Perry, John R. B., Grant, Struan F. A., Boomsma, Dorret I., Freathy, Rachel M., McCarthy, Mark I., Felix, Janine F., Sorensen, Thorkild I. A., and Tiemeier, Hen-Ning

Published
2019

225. Development of childhood asthma prediction models using machine learning approaches.

Author

Kothalawala, Dilini M., Murray, Clare S., Simpson, Angela, Custovic, Adnan, Tapper, William J., Arshad, S. Hasan, Holloway, John W., and Rezwan, Faisal I.

Subjects
ASTHMA in children, MACHINE learning, PREDICTION models, RECEIVER operating characteristic curves, ASTHMA
Abstract

Background: Respiratory symptoms are common in early life and often transient. It is difficult to identify in which children these will persist and result in asthma. Machine learning (ML) approaches have the potential for better predictive performance and generalisability over existing childhood asthma prediction models. This study applied ML approaches to predict school‐age asthma (age 10) in early life (Childhood Asthma Prediction in Early life, CAPE model) and at preschool age (Childhood Asthma Prediction at Preschool age, CAPP model). Methods: Clinical and environmental exposure data was collected from children enrolled in the Isle of Wight Birth Cohort (N = 1368, ∼15% asthma prevalence). Recursive Feature Elimination (RFE) identified an optimal subset of features predictive of school‐age asthma for each model. Seven state‐of‐the‐art ML classification algorithms were used to develop prognostic models. Training was performed by applying fivefold cross‐validation, imputation, and resampling. Predictive performance was evaluated on the test set. Models were further externally validated in the Manchester Asthma and Allergy Study (MAAS) cohort. Results: RFE identified eight and twelve predictors for the CAPE and CAPP models, respectively. Support Vector Machine (SVM) algorithms provided the best performance for both the CAPE (area under the receiver operating characteristic curve, AUC = 0.71) and CAPP (AUC = 0.82) models. Both models demonstrated good generalisability in MAAS (CAPE 8‐year = 0.71, 11‐year = 0.71, CAPP 8‐year = 0.83, 11‐year = 0.79) and excellent sensitivity to predict a subgroup of persistent wheezers. Conclusion: Using ML approaches improved upon the predictive performance of existing regression‐based models, with good generalisability and ability to rule in asthma and predict persistent wheeze. [ABSTRACT FROM AUTHOR]

Published
2021
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227. Maternal high-fat diet in mice alters immune regulation and lung function in the offspring.

Author

Losol, Purevsuren, Mercken, Lindert P., Fisk, Helena L., Calder, Philip C., Holloway, John W., and Torrens, Christopher

Subjects
LUNG physiology, UNSATURATED fatty acids, FAT content of food, INFLAMMATION, ANIMAL experimentation, BLOOD plasma, GENE expression, POLYMERASE chain reaction, ARACHIDONIC acid, PHOSPHOLIPIDS, MICE, CHILDREN
Abstract

PUFA modulate immune function and have been associated with the risk of childhood atopy and asthma. We investigated the effect of maternal fat intake in mice on PUFA status, elongase and desaturase gene expression, inflammatory markers and lung function in the offspring. C57BL/6J mice (n 32) were fed either standard chow (C, 20·4 % energy as fat) or a high-fat diet (HFD, 39·9 % energy as fat) for 4 weeks prior to conception and during gestation and lactation. At 21 d of age, offspring were weaned onto either the HFD or C, generating four experimental groups: C/C, C/HF, HF/C and HF/HF. Plasma and liver fatty acid composition were measured by GC and gene expression by quantitative PCR. Lung resistance to methacholine was assessed. Arachidonic acid concentrations in offspring plasma and liver phospholipids were increased by HFD; this effect was greater in the post-natal HFD group. DHA concentration in offspring liver phospholipids was increased in response to HFD and was higher in the post-natal HFD group. Post-natal HFD increased hepatic fatty acid desaturase (FADS) 2 and elongation of very long-chain fatty acid 5 expression in male offspring, whereas maternal HFD elevated expression of FADS1 and FADS2 in female offspring compared with males. Post-natal HFD increased expression of IL-6 and C-C motif chemokine ligand 2 (CCL2) in perivascular adipose tissue. The HFD lowered lung resistance to methacholine. Excessive maternal fat intake during development modifies hepatic PUFA status in offspring through regulation of gene expression of enzymes that are involved in PUFA biosynthesis and modifies the development of the offspring lungs leading to respiratory dysfunction. [ABSTRACT FROM AUTHOR]

Published
2021
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229. Association of the ADAM33 gene with asthma and bronchial hyperresponsiveness

Author

Van Eerdewegh, Paul, Little, Randall D., Dupuis, Josée, Del Mastro, Richard G., Falls, Kathy, Simon, Jason, Torrey, Dana, Pandit, Sunil, McKenny, Joyce, Braunschweiger, Karen, Walsh, Alison, Liu, Ziying, Hayward, Brooke, Folz, Colleen, Manning, Susan P., Bawa, Alicia, Saracino, Lisa, Thackston, Michelle, Benchekroun, Youssef, Capparell, Neva, Wang, Mei, Adair, Ron, Feng, Yun, Dubois, JoAnn, FitzGerald, Michael G., Huang, Hui, Gibson, René, Allen, Kristina M., Pedan, Alex, Danzig, Melvyn R., Umland, Shelby P., Egan, Robert W., Cuss, Francis M., Rorke, Steuart, Clough, Joanne B., Holloway, John W., Holgate, Stephen T., and Keith, Tim P.

Published
2002

231. Identification of ATPAF1 as a novel candidate gene for asthma in children

Author

Schauberger, Eric M., Ewart, Susan L., Arshad, Syed H., Huebner, Marianne, Karmaus, Wilfried, Holloway, John W., Friderici, Karen H., Ziegler, Julie T., Zhang, Hongmei, Rose-Zerilli, Matthew J., Barton, Sheila J., Holgate, Stephen T., Kilpatrick, Jeffrey R., Harley, John B., Lajoie-Kadoch, Stephane, Harley, Isaac T.W., Hamid, Qutayba, Kurukulaaratchy, Ramesh J., Seibold, Max A., Avila, Pedro C., Rodriguez-Cintrón, William, Rodriguez-Santana, Jose R., Hu, Donglei, Gignoux, Christopher, Romieu, Isabelle, London, Stephanie J., Burchard, Esteban G., Langefeld, Carl D., and Wills-Karp, Marsha

Published
2011

233. The interaction of genetic variants and DNA methylation of the interleukin-4 receptor gene increase the risk of asthma at age 18 years

Author

Soto-Ramírez Nelís, Arshad Syed Hasan, Holloway John W, Zhang Hongmei, Schauberger Eric, Ewart Susan, Patil Veeresh, and Karmaus Wilfried

Subjects
Interleukin-4 receptor gene, DNA methylation, Genetic variants, Asthma, Epigenetics, Medicine, Genetics, QH426-470
Abstract

Abstract Background The occurrence of asthma is weakly explained by known genetic variants. Epigenetic marks, DNA methylation (DNA-M) in particular, are considered to add to the explanation of asthma. However, no etiological model has yet been developed that integrates genetic variants and DNA-M. To explore a new model, we focused on one asthma candidate gene, the IL-4 receptor (IL4R). We hypothesized that genetic variants of IL4R in interaction with DNA-M at cytosine-phosphate-guanine (CpG) sites jointly alter the risk of asthma during adolescence. Blood samples were collected at age 18 years from 245 female cohort participants randomly selected for methylation analysis from a birth cohort (n = 1,456, Isle of Wight, UK). Genome-wide DNA-M was assessed using the Illumina Infinium HumanMethylation450 BeadChip. Results Thirteen single nucleotide polymorphisms (SNPs) and twelve CpG sites of IL4R gene were analyzed. Based on linkage disequilibrium and association with asthma, eight SNPs and one CpG site were selected for further analyses. Of the twelve CpG sites in the IL4R gene, only methylation levels of cg09791102 showed an association with asthma at age 18 years (Wilcoxon test: P = 0.01). Log-linear models were used to estimate risk ratios (RRs) for asthma adjusting for uncorrelated SNPs within the IL4R gene and covariates. Testing for interaction between the eight SNPs and the methylation levels of cg09791102 on the risk for asthma at age 18 years, we identified the statistically significant interaction term of SNP rs3024685 × methylation levels of cg09791102 (P = 0.002; after adjusting for false discovery rate). A total of 84 participants had methylation levels ≤0.88, 112 participants between 0.89 and 0.90, and 35 between 0.91 and 0.92. For the SNP rs3024685 (‘CC’ vs. ‘TT’) at methylation levels of ≤0.85, 0.86, 0.90, 0.91, and 0.92, the RRs were 0.01, 0.04, 4.65, 14.76, 14.90, respectively (interaction effect, P = 0.0003). Conclusions Adjusting for multiple testing, our results suggest that DNA-M modulates the risk of asthma related to genetic variants in the IL4R gene. The strong interaction of one SNP and DNA-M is encouraging and provides a novel model of how a joint effect of genetic variants and DNA-M can explain occurrence of asthma.

Published
2013
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235. In that case

Author

Holloway, John W and Wee, Richman

Published
2002

237. BMI trajectory in childhood is associated with asthma incidence at young adulthood mediated by DNA methylation.

Author

Rathod, Rutu, Zhang, Hongmei, Karmaus, Wilfried, Ewart, Susan, Kadalayil, Latha, Relton, Caroline, Ring, Susan, Arshad, S. Hasan, and Holloway, John W.

Subjects
YOUNG adults, ASTHMA, WHEEZE, DNA methylation, ASTHMA in children, BODY mass index
Abstract

Purpose: Body mass index (BMI) is associated with asthma but associations of BMI temporal patterns with asthma incidence are unclear. Previous studies suggest that DNA methylation (DNAm) is associated with asthma status and variation in DNAm is a consequence of BMI changes. This study assessed the direct and indirect (via DNAm) effects of BMI trajectories in childhood on asthma incidence at young adulthood. Methods: Data from the Isle of Wight (IoW) birth cohort were included in the analyses. Group-based trajectory modelling was applied to infer latent BMI trajectories from ages 1 to 10 years. An R package, ttscreening, was applied to identify differentially methylated CpGs at age 10 years associated with BMI trajectories, stratified for sex. Logistic regressions were used to further exclude CpGs with DNAm at age 10 years not associated with asthma incidence at 18 years. CpGs discovered via path analyses that mediated the association of BMI trajectories with asthma incidence in the IoW cohort were further tested in an independent cohort, the Avon Longitudinal Study of Children and Parents (ALSPAC). Results: Two BMI trajectories (high vs. normal) were identified. Of the 442,474 CpG sites, DNAm at 159 CpGs in males and 212 in females were potentially associated with BMI trajectories. Assessment of their association with asthma incidence identified 9 CpGs in males and 6 CpGs in females. DNAm at 4 of these 15 CpGs showed statistically significant mediation effects (p-value < 0.05). At two of the 4 CpGs (cg23632109 and cg10817500), DNAm completely mediated the association (i.e., only statistically significant indirect effects were identified). In the ALSPAC cohort, at all four CpGs, the same direction of mediating effects were observed as those found in the IoW cohort, although statistically insignificant. Conclusion: The association of BMI trajectory in childhood with asthma incidence at young adulthood is possibly mediated by DNAm. [ABSTRACT FROM AUTHOR]

Published
2021
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239. GWAS on longitudinal growth traits reveals different genetic factors influencing infant, child, and adult BMI

Author

Couto Alves, Alexessander, De Silva, N. Maneka G., Karhunen, Ville, Sovio, Ulla, Das, Shikta, Taal, H. Rob, Warrington, Nicole M., Lewin, Alexandra M., Kaakinen, Marika, Cousminer, Diana L., Thiering, Elisabeth, Timpson, Nicholas J., Bond, Tom A., Lowry, Estelle, Brown, Christopher D., Estivill, Xavier, Lindi, Virpi, Bradfield, Jonathan P., Geller, Frank, Speed, Doug, Coin, Lachlan J. M., Loh, Marie, Barton, Sheila J., Beilin, Lawrence J., Bisgaard, Hans, Bønnelykke, Klaus, Alili, Rohia, Hatoum, Ida J., Schramm, Katharina, Cartwright, Rufus, Charles, Marie-Aline, Salerno, Vincenzo, Clément, Karine, Claringbould, Annique A. J., van Duijn, Cornelia M., Moltchanova, Elena, Eriksson, Johan G., Elks, Cathy, Feenstra, Bjarke, Flexeder, Claudia, Franks, Stephen, Frayling, Timothy M., Freathy, Rachel M., Elliott, Paul, Widén, Elisabeth, Hakonarson, Hakon, Hattersley, Andrew T., Rodriguez, Alina, Banterle, Marco, Heinrich, Joachim, Heude, Barbara, Holloway, John W., Hofman, Albert, Hyppönen, Elina, Inskip, Hazel, Kaplan, Lee M., Hedman, Asa K., Läärä, Esa, Prokisch, Holger, Grallert, Harald, Lakka, Timo A., Lawlor, Debbie A., Melbye, Mads, Ahluwalia, Tarunveer S., Marinelli, Marcella, Millwood, Iona Y., Palmer, Lyle J., Pennell, Craig E., Perry, John R., Ring, Susan M., Savolainen, Markku J., Rivadeneira, Fernando, Standl, Marie, Sunyer, Jordi, Tiesler, Carla M. T., Uitterlinden, Andre G., Schierding, William, O’Sullivan, Justin M., Prokopenko, Inga, Herzig, Karl-Heinz, Smith, George Davey, O'Reilly, Paul, Felix, Janine F., Buxton, Jessica L., Blakemore, Alexandra I. F., Ong, Ken K., Jaddoe, Vincent W. V., Grant, Struan F. A., Sebert, Sylvain, McCarthy, Mark I., and Järvelin, Marjo-Riitta

Subjects
ddc
Published
2018

240. Omics and Lung Function: A Need for Integration.

Author

Holloway, John W. and DeMeo, Dawn L.

Abstract

The article explores the role of DNA methylation in a wide range of biological processes, including regulation of gene expression, reproduction, and development and in chronic diseases and aging. It mentions that maternal tobacco smoke exposure has shown highly specific changes in the offspring's epigenome at birth that persist for decades.

Published
2022
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241. Cohort Profile: Pregnancy And Childhood Epigenetics (PACE) Consortium

Author

Felix, Janine F., Joubert, Bonnie R., Baccarelli, Andrea A., Sharp, Gemma C., Almqvist, Catarina, Annesi-Maesano, Isabella, Arshad, Hasan, Baïz, Nour, Bakermans-Kranenburg, Marian J., Bakulski, Kelly M., Binder, Elisabeth B., Bouchard, Luigi, Breton, Carrie V., Brunekreef, Bert, Brunst, Kelly J., Burchard, Esteban G., Bustamante, Mariona, Chatzi, Leda, Munthe-Kaas, Monica Cheng, Corpeleijn, Eva, Czamara, Darina, Dabelea, Dana, Smith, George Davey, De Boever, Patrick, Duijts, Liesbeth, Dwyer, Terence, Eng, Celeste, Eskenazi, Brenda, Everson, Todd M., Falahi, Fahimeh, Fallin, M. Daniele, Farchi, Sara, Fernández, Mariana F., Gao, Lu, Gaunt, Tom R., Ghantous, Akram, Gillman, Matthew W., Gonseth, Semira, Grote, Veit, Gruzieva, Olena, Håberg, Siri Eldevik, Herceg, Zdenko, Hivert, Marie-France, Holland, Nina, Holloway, John W., Hoyo, Cathrine, Hu, Donglei, Huang, Rae-Chi, Huen, Karen, Järvelin, Marjo-Riitta, Jima, Dereje D., Just, Allan C., Karagas, Margaret R., Magnus, Per, Nystad, Wenche, Page, Christian, Lie, Rolv T., and Magnus, Maria Christine

Abstract

publishedVersion

Published
2018

242. Cohort Profile: Pregnancy And Childhood Epigenetics (PACE) Consortium

Author

Felix, Janine F, Joubert, Bonnie R, Baccarelli, Andrea A, Sharp, Gemma C, Almqvist, Catarina, Annesi-Maesano, Isabella, Arshad, S. Hasan, Baïz, Nour, Bakermans-Kranenburg, Marian J., Bakulski, Kelly M, Binder, Elisabeth B, Bouchard, Luigi, Breton, Carrie V, Brunekreef, Bert, Brunst, Kelly J, Burchard, Esteban G., Bustamante, Mariona, Chatzi, Leda, Cheng Munthe-Kaas, Monica, Corpeleijn, Eva, Czamara, Darina, Dabelea, Dana, Davey Smith, George, De Boever, Patrick, Duijts, Liesbeth, Dwyer, Terence, Eng, Celeste, Eskenazi, Brenda, Everson, Todd M, Falahi, Fahimeh, Fallin, M Daniele, Farchi, Sara, Fernandez, Mariana F., Gao, Lu, Gaunt, Tom R, Ghantous, Akram, Gillman, Matthew W, Gonseth, Semira, Grote, Veit, Gruzieva, Olena, Håberg, Siri E, Herceg, Zdenko, Hivert, Marie-France, Holland, Nina, Holloway, John W, Hoyo, Cathrine, Hu, Donglei, Huang, Rae-Chi, Huen, Karen, Järvelin, Marjo-Riitta, Jima, Dereje D, Just, Allan C, Karagas, Margaret R, Karlsson, Robert, Karmaus, Wilfried, Kechris, Katerina J, Kere, Juha, Kogevinas, Manolis, Koletzko, Berthold, Koppelman, Gerard H, Küpers, Leanne K., Ladd-Acosta, Christine, Lahti, Jari, Lambrechts, Nathalie, Langie, Sabine A S, Lie, Rolv T, Liu, Andrew H, Magnus, Maria C, Magnus, Per, Maguire, Rachel L, Marsit, Carmen J, McArdle, Wendy, Melén, Erik, Melton, Phillip, Murphy, Susan K, Nawrot, Tim S, Nisticò, Lorenza, Nohr, Ellen A, Nordlund, Björn, Nystad, Wenche, Oh, Sam S, Oken, Emily, Page, Christian M, Perron, Patrice, Pershagen, Göran, Pizzi, Costanza, Plusquin, Michelle, Raikkonen, Katri, Reese, Sarah E, Reischl, Eva, Richiardi, Lorenzo, Ring, Susan M, Roy, Ritu P, Rzehak, Peter, Schoeters, Greet, Schwartz, David A, Sebert, Sylvain, Snieder, Harold, Sørensen, Thorkild I A, Starling, Anne P, Sunyer, Jordi, Taylor, Jack A, Tiemeier, Henning, Ullemar, Vilhelmina, Vafeiadi, Marina, van IJzendoorn, Marinus H, Vonk, Judith M, Vriens, Annette, Vrijheid, Martine, Wang, Pei, Wiemels, Joseph L, Wilcox, Allen J, Wright, Rosalind J, Xu, Cheng-Jian, Xu, Zongli, Yang, Ivana V, Yousefi, Paul, Zhang, Hongmei, Zhang, Weiming, Zhao, Shanshan, Agha, Golareh, Relton, Caroline L, Jaddoe, Vincent W V, London, Stephanie J, dIRAS RA-2, and One Health Chemisch

Published
2018

244. Duration of breastfeeding is associated with leptin (LEP) DNA methylation profiles and BMI in 10-year-old children

Author

Sherwood, William B., primary, Bion, Victoria, additional, Lockett, Gabrielle A., additional, Ziyab, Ali H., additional, Soto-Ramírez, Nelís, additional, Mukherjee, Nandini, additional, Kurukulaaratchy, Ramesh J., additional, Ewart, Susan, additional, Zhang, Hongmei, additional, Arshad, S. Hasan, additional, Karmaus, Wilfried, additional, Holloway, John W., additional, and Rezwan, Faisal I., additional

Published
2019
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245. Reply

Author

Knudsen, Toril Mørkve, primary, Rezwan, Faisal I., additional, Svanes, Cecilie, additional, and Holloway, John W., additional

Published
2019
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246. Hypertensive Disorders of Pregnancy and DNA Methylation in Newborns

Author

Kazmi, Nabila, primary, Sharp, Gemma C., additional, Reese, Sarah E., additional, Vehmeijer, Florianne O., additional, Lahti, Jari, additional, Page, Christian M., additional, Zhang, Weiming, additional, Rifas-Shiman, Sheryl L., additional, Rezwan, Faisal I., additional, Simpkin, Andrew J., additional, Burrows, Kimberley, additional, Richardson, Tom G., additional, Santos Ferreira, Diana L., additional, Fraser, Abigail, additional, Harmon, Quaker E., additional, Zhao, Shanshan, additional, Jaddoe, Vincent W.V., additional, Czamara, Darina, additional, Binder, Elisabeth B., additional, Magnus, Maria C., additional, Håberg, Siri E., additional, Nystad, Wenche, additional, Nohr, Ellen A., additional, Starling, Anne P., additional, Kechris, Katerina J., additional, Yang, Ivana V., additional, DeMeo, Dawn L., additional, Litonjua, Augusto A., additional, Baccarelli, Andrea, additional, Oken, Emily, additional, Holloway, John W., additional, Karmaus, Wilfried, additional, Arshad, Syed H., additional, Dabelea, Dana, additional, Sørensen, Thorkild I.A., additional, Laivuori, Hannele, additional, Raikkonen, Katri, additional, Felix, Janine F., additional, London, Stephanie J., additional, Hivert, Marie-France, additional, Gaunt, Tom R., additional, Lawlor, Debbie A., additional, and Relton, Caroline L., additional

Published
2019
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247. Epigenome-wide association study of asthma and wheeze characterizes loci within HK1

Author

Everson, Todd M., primary, Zhang, Hongmei, additional, Lockett, Gabrielle A., additional, Kaushal, Akhilesh, additional, Forthofer, Melinda, additional, Ewart, Susan L., additional, Burrows, Kimberley, additional, Relton, Caroline L., additional, Sharp, Gemma C., additional, Henderson, A. John, additional, Patil, Veeresh K., additional, Rezwan, Faisal I., additional, Arshad, S. Hasan, additional, Holloway, John W., additional, and Karmaus, Wilfried, additional

Published
2019
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248. Distinguishing Wheezing Phenotypes from Infancy to Adolescence. A Pooled Analysis of Five Birth Cohorts

Author

Oksel, Ceyda, primary, Granell, Raquel, additional, Haider, Sadia, additional, Fontanella, Sara, additional, Simpson, Angela, additional, Turner, Steve, additional, Devereux, Graham, additional, Arshad, Syed Hasan, additional, Murray, Clare S., additional, Roberts, Graham, additional, Holloway, John W., additional, Cullinan, Paul, additional, Henderson, John, additional, Custovic, Adnan, additional, Curtin, John, additional, Colicino, Silvia, additional, Woodcock, Ashley, additional, Bush, Andrew, additional, Saglani, Sejal, additional, Lloyd, Clare M., additional, Marsland, Benjamin, additional, Grigg, Jonathan, additional, Schwarze, Jurgen, additional, Shields, Mike, additional, Ghazal, Peter, additional, and Power, Multan, additional

Published
2019
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249. DNA methylation links prenatal smoking exposure to later life health outcomes in offspring

Author

Wiklund, Petri, primary, Karhunen, Ville, additional, Richmond, Rebecca C., additional, Parmar, Priyanka, additional, Rodriguez, Alina, additional, De Silva, Maneka, additional, Wielscher, Matthias, additional, Rezwan, Faisal I., additional, Richardson, Tom G., additional, Veijola, Juha, additional, Herzig, Karl-Heinz, additional, Holloway, John W., additional, Relton, Caroline L., additional, Sebert, Sylvain, additional, and Järvelin, Marjo-Riitta, additional

Published
2019
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