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

Author

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

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

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

Published
2019

2. Life-Course Genome-wide Association Study Meta-analysis of Total Body BMD and Assessment of Age-Specific Effects

Author

Medina-Gomez, Carolina, Kemp, John P, Trajanoska, Katerina, Luan, Jian’an, Chesi, Alessandra, Ahluwalia, Tarunveer S, Mook-Kanamori, Dennis O, Ham, Annelies, Hartwig, Fernando P, Evans, Daniel S, Joro, Raimo, Nedeljkovic, Ivana, Zheng, Hou-Feng, Zhu, Kun, Atalay, Mustafa, Liu, Ching-Ti, Nethander, Maria, Broer, Linda, Porleifsson, Gudmar, Mullin, Benjamin H, Handelman, Samuel K, Nalls, Mike A, Jessen, Leon E, Heppe, Denise HM, Richards, J Brent, Wang, Carol, Chawes, Bo, Schraut, Katharina E, Amin, Najaf, Wareham, Nick, Karasik, David, Van der Velde, Nathalie, Ikram, M Arfan, Zemel, Babette S, Zhou, Yanhua, Carlsson, Christian J, Liu, Yongmei, McGuigan, Fiona E, Boer, Cindy G, Bønnelykke, Klaus, Ralston, Stuart H, Robbins, John A, Walsh, John P, Zillikens, M Carola, Langenberg, Claudia, Li-Gao, Ruifang, Williams, Frances MK, Harris, Tamara B, Akesson, Kristina, Jackson, Rebecca D, Sigurdsson, Gunnar, Heijer, Martin den, van der Eerden, Bram CJ, van de Peppel, Jeroen, Spector, Timothy D, Pennell, Craig, Horta, Bernardo L, Felix, Janine F, Zhao, Jing Hua, Wilson, Scott G, de Mutsert, Renée, Bisgaard, Hans, Styrkársdóttir, Unnur, Jaddoe, Vincent W, Orwoll, Eric, Lakka, Timo A, Scott, Robert, Grant, Struan FA, Lorentzon, Mattias, van Duijn, Cornelia M, Wilson, James F, Stefansson, Kari, Psaty, Bruce M, Kiel, Douglas P, Ohlsson, Claes, Ntzani, Evangelia, van Wijnen, Andre J, Forgetta, Vincenzo, Ghanbari, Mohsen, Logan, John G, Williams, Graham R, Bassett, JH Duncan, Croucher, Peter I, Evangelou, Evangelos, Uitterlinden, Andre G, Ackert-Bicknell, Cheryl L, Tobias, Jonathan H, Evans, David M, and Rivadeneira, Fernando

Subjects
Rare Diseases, Aging, Human Genome, Osteoporosis, Clinical Research, Genetics, Aetiology, 2.1 Biological and endogenous factors, Musculoskeletal, Good Health and Well Being, Adolescent, Age Factors, Animals, Bone Density, Child, Child, Preschool, Genetic Loci, Genome-Wide Association Study, Humans, Infant, Infant, Newborn, Mice, Knockout, Polymorphism, Single Nucleotide, Quantitative Trait, Heritable, Regression Analysis, BMD, CREB3L1, ESR1, GWASs, RANKL, age-dependent effects, bone mineral density, fracture, genetic correlation, genome-wide association studies, meta-regression, total-body DXA, Biological Sciences, Medical and Health Sciences, Genetics & Heredity
Abstract

Bone mineral density (BMD) assessed by DXA is used to evaluate bone health. In children, total body (TB) measurements are commonly used; in older individuals, BMD at the lumbar spine (LS) and femoral neck (FN) is used to diagnose osteoporosis. To date, genetic variants in more than 60 loci have been identified as associated with BMD. To investigate the genetic determinants of TB-BMD variation along the life course and test for age-specific effects, we performed a meta-analysis of 30 genome-wide association studies (GWASs) of TB-BMD including 66,628 individuals overall and divided across five age strata, each spanning 15 years. We identified variants associated with TB-BMD at 80 loci, of which 36 have not been previously identified; overall, they explain approximately 10% of the TB-BMD variance when combining all age groups and influence the risk of fracture. Pathway and enrichment analysis of the association signals showed clustering within gene sets implicated in the regulation of cell growth and SMAD proteins, overexpressed in the musculoskeletal system, and enriched in enhancer and promoter regions. These findings reveal TB-BMD as a relevant trait for genetic studies of osteoporosis, enabling the identification of variants and pathways influencing different bone compartments. Only variants in ESR1 and close proximity to RANKL showed a clear effect dependency on age. This most likely indicates that the majority of genetic variants identified influence BMD early in life and that their effect can be captured throughout the life course.

Published
2018

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

Author

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

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

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

Published
2016

4. Bone mineral density loci specific to the skull portray potential pleiotropic effects on craniosynostosis

Author

Medina-Gomez, Carolina, primary, Mullin, Benjamin H., additional, Chesi, Alessandra, additional, Prijatelj, Vid, additional, Kemp, John P., additional, Shochat-Carvalho, Chen, additional, Trajanoska, Katerina, additional, Wang, Carol, additional, Joro, Raimo, additional, Evans, Tavia E., additional, Schraut, Katharina E., additional, Li-Gao, Ruifang, additional, Ahluwalia, Tarunveer S., additional, Zillikens, M. Carola, additional, Zhu, Kun, additional, Mook-Kanamori, Dennis O., additional, Evans, Daniel S., additional, Nethander, Maria, additional, Knol, Maria J., additional, Thorleifsson, Gudmar, additional, Prokic, Ivana, additional, Zemel, Babette, additional, Broer, Linda, additional, McGuigan, Fiona E., additional, van Schoor, Natasja M., additional, Reppe, Sjur, additional, Pawlak, Mikolaj A., additional, Ralston, Stuart H., additional, van der Velde, Nathalie, additional, Lorentzon, Mattias, additional, Stefansson, Kari, additional, Adams, Hieab H. H., additional, Wilson, Scott G., additional, Ikram, M. Arfan, additional, Walsh, John P., additional, Lakka, Timo A., additional, Gautvik, Kaare M., additional, Wilson, James F., additional, Orwoll, Eric S., additional, van Duijn, Cornelia M., additional, Bønnelykke, Klaus, additional, Uitterlinden, Andre G., additional, Styrkársdóttir, Unnur, additional, Akesson, Kristina E., additional, Spector, Timothy D., additional, Tobias, Jonathan H., additional, Ohlsson, Claes, additional, Felix, Janine F., additional, Bisgaard, Hans, additional, Grant, Struan F. A., additional, Richards, J. Brent, additional, Evans, David M., additional, van der Eerden, Bram, additional, van de Peppel, Jeroen, additional, Ackert-Bicknell, Cheryl, additional, Karasik, David, additional, Kague, Erika, additional, and Rivadeneira, Fernando, additional

Published
2023
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5. Bone mineral density loci specific to the skull portray potential pleiotropic effects on craniosynostosis

Author

Medina-Gomez, Carolina, Mullin, Benjamin H, Chesi, Alessandra, Prijatelj, Vid, Kemp, John P, Shochat-Carvalho, Chen, Trajanoska, Katerina, Wang, Carol, Joro, Raimo, Evans, Tavia E, Schraut, Katharina E, Li-Gao, Ruifang, Ahluwalia, Tarunveer S, Zillikens, M Carola, Zhu, Kun, Mook-Kanamori, Dennis O, Evans, Daniel S, Nethander, Maria, Knol, Maria J, Thorleifsson, Gudmar, Prokic, Ivana, Zemel, Babette, Broer, Linda, McGuigan, Fiona E, van Schoor, Natasja M, Reppe, Sjur, Pawlak, Mikolaj A, Ralston, Stuart H, van der Velde, Nathalie, Lorentzon, Mattias, Stefansson, Kari, Adams, Hieab H H, Wilson, Scott G, Ikram, M Arfan, Walsh, John P, Lakka, Timo A, Gautvik, Kaare M, Wilson, James F, Orwoll, Eric S, van Duijn, Cornelia M, Bønnelykke, Klaus, Uitterlinden, Andre G, Styrkársdóttir, Unnur, Akesson, Kristina E, Spector, Timothy D, Tobias, Jonathan H, Ohlsson, Claes, Felix, Janine F, Bisgaard, Hans, Grant, Struan F A, Richards, J Brent, Evans, David M, van der Eerden, Bram, van de Peppel, Jeroen, Ackert-Bicknell, Cheryl, Karasik, David, Kague, Erika, and Rivadeneira, Fernando

Subjects
Bone Density/genetics, Skull, Transcription Factors/genetics, Animals, Genome-Wide Association Study, Zebrafish/genetics, Craniosynostoses/genetics
Abstract

Skull bone mineral density (SK-BMD) provides a suitable trait for the discovery of key genes in bone biology, particularly to intramembranous ossification, not captured at other skeletal sites. We perform a genome-wide association meta-analysis (n ~ 43,800) of SK-BMD, identifying 59 loci, collectively explaining 12.5% of the trait variance. Association signals cluster within gene-sets involved in skeletal development and osteoporosis. Among the four novel loci (ZIC1, PRKAR1A, AZIN1/ATP6V1C1, GLRX3), there are factors implicated in intramembranous ossification and as we show, inherent to craniosynostosis processes. Functional follow-up in zebrafish confirms the importance of ZIC1 on cranial suture patterning. Likewise, we observe abnormal cranial bone initiation that culminates in ectopic sutures and reduced BMD in mosaic atp6v1c1 knockouts. Mosaic prkar1a knockouts present asymmetric bone growth and, conversely, elevated BMD. In light of this evidence linking SK-BMD loci to craniofacial abnormalities, our study provides new insight into the pathophysiology, diagnosis and treatment of skeletal diseases. Skull bone mineral density (SK-BMD) provides a suitable trait for the discovery of key genes in bone biology, particularly to intramembranous ossification, not captured at other skeletal sites. We perform a genome-wide association meta-analysis (n ~ 43,800) of SK-BMD, identifying 59 loci, collectively explaining 12.5% of the trait variance. Association signals cluster within gene-sets involved in skeletal development and osteoporosis. Among the four novel loci (ZIC1, PRKAR1A, AZIN1/ATP6V1C1, GLRX3), there are factors implicated in intramembranous ossification and as we show, inherent to craniosynostosis processes. Functional follow-up in zebrafish confirms the importance of ZIC1 on cranial suture patterning. Likewise, we observe abnormal cranial bone initiation that culminates in ectopic sutures and reduced BMD in mosaic atp6v1c1 knockouts. Mosaic prkar1a knockouts present asymmetric bone growth and, conversely, elevated BMD. In light of this evidence linking SK-BMD loci to craniofacial abnormalities, our study provides new insight into the pathophysiology, diagnosis and treatment of skeletal diseases.

Published
2023

6. Genetics of early-life head circumference and genetic correlations with neurological, psychiatric and cognitive outcomes

Author

Vogelezang, Suzanne, Bradfield, Jonathan P., Johansson, Stefan, Stergiakouli, Evie, Thiering, Elisabeth, Pennell, Craig E., Ahluwalia, Tarunveer S., Karhunen, Ville, Scholz, Markus, Liu, Xueping, Iñiguez, Carmen, Raitakari, Olli T., Bacelis, Jonas, Schnurr, Theresia M., Lakka, Timo A., Ntalla, Ioanna, Lind, Mads V., Lauritzen, Lotte, Herrala, Sauli, Lin, Frederick T. J., Frithioff-Bøjsøe, Christine, Beaumont, Robin N., Zafarmand, Mohammed H., Rzehak, Peter, Bilbao, Jose R., Junna, Nella, Vonk, Judith M., Rifas-Shiman, Sheryl L., Janjanam, Vimala D., Knol, Maria J., Ramdas, Shweta, Beilin, Lawrie, Bønnelykke, Klaus, Casas, Maribel, Eriksson, Johan G., Escribano, Joaquin, Evans, Tavia E., Gehring, Ulrike, Geller, Frank, Grote, Veit, Gruszfeld, Darek, Hakonarson, Hakon, Hattersley, Andrew T., Have, Christian T., Geoffrey Hayes, M., Heinrich, Joachim, Helgeland, Øvind, Holloway, Jhon, Joro, Raimo, Juodakis, Julius, Knight, Bridget A., Koletzko, Bert, Körner, Antje, Langhendries, Jean-Paul, Leinonen, Jaakko T., Lindi, Virpi, Lund, Morten A. V., Lye, Stephen, Melbye, Mads, Michaelsen, Kim F., Morgen, Camilla S., Niinikoski, Harri, Pahkala, Katja, Panoutsopoulou, Kalliope, Pedersen, Oluf, Rivadeneira, Fernando, Santa-Marina, Loreto, Schaik, Barbera D. C., Scholtens, Denise, Sebert, Sylvain, Tamayo, Ibon, Timpson, Nicholas J., Torrent, Maties, Uitterlinden, André G., Vaudel, Marc, Verduci, Elvira, Vinding, Rebecca, Vogel, Mandy, Zeggini, Eleftheria, Brown, Christopher, Adams, Hieab H. H., Karmaus, Wilfried, Hivert, Marie-France, Koppelman, Gerard H., Widén, Elisabeth, Fernandez-Jimenez, Nora, Waldenberger, Melanie, Vrijkotte, Tanja G. M., Freathy, Rachel M., Holm, Jens-Christian, Lowe, William L., Grarup, Niels, Hansen, Torben, Dedoussis, George V., Atalay, Mustafa, Nohr, Ellen A., Jacobsson, Bo, Pitkänen, Niina, Vrijheid, Martine, Feenstra, Bjarke, Kiess, Wieland, Jarvelin, Marjo-Riita, Bisgaard, Hans, Wang C, Carol, Standl, Marie, McCarthy, Mark I., Pourcain, Beate St, Njølstad, Pål R., Grant, Struan F. A., Felix, Janine F., Jaddoe, Vincent W. V., Epidemiology, Pediatrics, Radiology & Nuclear Medicine, Internal Medicine, Clinical Genetics, and Groningen Research Institute for Asthma and COPD (GRIAC)

Subjects
Adult, Genome-wide association study, Genetic correlations, Infancy, Head circumference, Genetic Correlations, Genome-wide Association Study, Head Circumference, Cognition, Phenotype, Genetics, Genome-Wide Association Study/methods, Educational Status, Humans, Child, Genetics (clinical), Genome-Wide Association Study, Bristol Population Health Science Institute
Abstract

Background Head circumference is associated with intelligence and tracks from childhood into adulthood. Methods We performed a genome-wide association study meta-analysis and follow-up of head circumference in a total of 29,192 participants between 6 and 30 months of age. Results Seven loci reached genome-wide significance in the combined discovery and replication analysis of which three loci near ARFGEF2, MYCL1, and TOP1, were novel. We observed positive genetic correlations for early-life head circumference with adult intracranial volume, years of schooling, childhood and adult intelligence, but not with adult psychiatric, neurological, or personality-related phenotypes. Conclusions The results of this study indicate that the biological processes underlying early-life head circumference overlap largely with those of adult head circumference. The associations of early-life head circumference with cognitive outcomes across the life course are partly explained by genetics.

Published
2022

7. Genome Wide Association Metanalysis Of Skull Bone Mineral Density Identifies Loci Relevant For Osteoporosis And Craniosynostosis

Author

Medina-Gomez, Carolina, primary, Mullin, Benjamin H., additional, Chesi, Alessandra, additional, Prijatelj, Vid, additional, Kemp, John P., additional, Shochat-Carvalho, Chen, additional, Trajanoska, Katerina, additional, Wang, Carol, additional, Joro, Raimo, additional, Evans, Tavia E., additional, Schraut, Katharina E., additional, Li-Gao, Ruifang, additional, Ahluwalia, Tarunveer S., additional, Zillikens, M. Carola, additional, Zhu, Kun, additional, Mook-Kanamori, Dennis O., additional, Evans, Daniel S., additional, Nethander, Maria, additional, Knol, Maria J., additional, Thorleifsson, Gudmar, additional, Prokic, Ivana, additional, Zemel, Babette, additional, Broer, Linda, additional, van Schoor, Natasja, additional, Reppe, Sjur, additional, Pawlak, Mikolaj A., additional, Ralston, Stuart H., additional, van der Velde, Nathalie, additional, Lorentzon, Mattias, additional, Stefansson, Kari, additional, Adams, Hieab H.H., additional, Wilson, Scott G., additional, Ikram, M. Arfan, additional, Walsh, John P., additional, Lakka, Timo A., additional, Gautvik, Kaare M., additional, Wilson, James F, additional, Orwoll, Eric S., additional, van Duijn, Cornelia M., additional, Bønnelykke, Klaus, additional, Uitterlinden, Andre G., additional, Stykársdóttir, Unnur, additional, Spector, Timothy D., additional, Tobias, Jonathan H, additional, Ohlsson, Claes, additional, Felix, Janine F., additional, Bisgaard, Hans, additional, Grant, Struan F.A., additional, Richards, J. Brent, additional, Evans, David M., additional, van der Eerden, Bram, additional, van de Peppel, Jeroen, additional, Ackert-Bicknell, Cheryl, additional, Karasik, David, additional, Kague, Erika, additional, and Rivadeneira, Fernando, additional

Published
2021
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8. Genome-wide association analysis identifies three new susceptibility loci for childhood body mass index

Author

Felix, Janine F., Bradfield, Jonathan P., Monnereau, Claire, van der Valk, Ralf J.P., Stergiakouli, Evie, Chesi, Alessandra, Gaillard, Romy, Feenstra, Bjarke, Thiering, Elisabeth, Kreiner-Møller, Eskil, Mahajan, Anubha, Pitkänen, Niina, Joro, Raimo, Cavadino, Alana, Huikari, Ville, Franks, Steve, Groen-Blokhuis, Maria M., Cousminer, Diana L., Marsh, Julie A., Lehtimäki, Terho, Curtin, John A., Vioque, Jesus, Ahluwalia, Tarunveer S., Myhre, Ronny, Price, Thomas S., Vilor-Tejedor, Natalia, Yengo, Loïc, Grarup, Niels, Ntalla, Ioanna, Ang, Wei, Atalay, Mustafa, Bisgaard, Hans, Blakemore, Alexandra I., Bonnefond, Amelie, Carstensen, Lisbeth, Eriksson, Johan, Flexeder, Claudia, Franke, Lude, Geller, Frank, Geserick, Mandy, Hartikainen, Anna-Liisa, Haworth, Claire M.A., Hirschhorn, Joel N., Hofman, Albert, Holm, Jens-Christian, Horikoshi, Momoko, Hottenga, Jouke Jan, Huang, Jinyan, Kadarmideen, Haja N., Kähönen, Mika, Kiess, Wieland, Lakka, Hanna-Maaria, Lakka, Timo A., Lewin, Alexandra M., Liang, Liming, Lyytikäinen, Leo-Pekka, Ma, Baoshan, Magnus, Per, McCormack, Shana E., McMahon, George, Mentch, Frank D., Middeldorp, Christel M., Murray, Clare S., Pahkala, Katja, Pers, Tune H., Pfäffle, Roland, Postma, Dirkje S., Power, Christine, Simpson, Angela, Sengpiel, Verena, Tiesler, Carla M. T., Torrent, Maties, Uitterlinden, André G., van Meurs, Joyce B., Vinding, Rebecca, Waage, Johannes, Wardle, Jane, Zeggini, Eleftheria, Zemel, Babette S., Dedoussis, George V., Pedersen, Oluf, Froguel, Philippe, Sunyer, Jordi, Plomin, Robert, Jacobsson, Bo, Hansen, Torben, Gonzalez, Juan R., Custovic, Adnan, Raitakari, Olli T., Pennell, Craig E., Widén, Elisabeth, Boomsma, Dorret I., Koppelman, Gerard H., Sebert, Sylvain, Järvelin, Marjo-Riitta, Hyppönen, Elina, McCarthy, Mark I., Lindi, Virpi, Harri, Niinikoski, Körner, Antje, Bønnelykke, Klaus, Heinrich, Joachim, Melbye, Mads, Rivadeneira, Fernando, Hakonarson, Hakon, Ring, Susan M., Smith, George Davey, Sørensen, Thorkild I.A., Timpson, Nicholas J., Grant, Struan F.A., Jaddoe, Vincent W.V., Kalkwarf, Heidi J., Lappe, Joan M., Gilsanz, Vicente, Oberfield, Sharon E., Shepherd, John A., Kelly, Andrea, and Zemel, Babette S.

Published
2016
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9. A novel common variant in DCST2 is associated with length in early life and height in adulthood

Author

van der Valk, Ralf J.P., Kreiner-Møller, Eskil, Kooijman, Marjolein N., Guxens, Mònica, Stergiakouli, Evangelia, Sääf, Annika, Bradfield, Jonathan P., Geller, Frank, Hayes, M. Geoffrey, Cousminer, Diana L., Körner, Antje, Thiering, Elisabeth, Curtin, John A., Myhre, Ronny, Huikari, Ville, Joro, Raimo, Kerkhof, Marjan, Warrington, Nicole M., Pitkänen, Niina, Ntalla, Ioanna, Horikoshi, Momoko, Veijola, Riitta, Freathy, Rachel M., Teo, Yik-Ying, Barton, Sheila J., Evans, David M., Kemp, John P., St Pourcain, Beate, Ring, Susan M., Davey Smith, George, Bergström, Anna, Kull, Inger, Hakonarson, Hakon, Mentch, Frank D., Bisgaard, Hans, Chawes, Bo, Stokholm, Jakob, Waage, Johannes, Eriksen, Patrick, Sevelsted, Astrid, Melbye, Mads, van Duijn, Cornelia M., Medina-Gomez, Carolina, Hofman, Albert, de Jongste, Johan C., Taal, H. Rob, Uitterlinden, André G., Armstrong, Loren L., Eriksson, Johan, Palotie, Aarno, Bustamante, Mariona, Estivill, Xavier, Gonzalez, Juan R., Llop, Sabrina, Kiess, Wieland, Mahajan, Anubha, Flexeder, Claudia, Tiesler, Carla M.T., Murray, Clare S., Simpson, Angela, Magnus, Per, Sengpiel, Verena, Hartikainen, Anna-Liisa, Keinanen-Kiukaanniemi, Sirkka, Lewin, Alexandra, Da Silva Couto Alves, Alexessander, Blakemore, Alexandra I., Buxton, Jessica L., Kaakinen, Marika, Rodriguez, Alina, Sebert, Sylvain, Vaarasmaki, Marja, Lakka, Timo, Lindi, Virpi, Gehring, Ulrike, Postma, Dirkje S., Ang, Wei, Newnham, John P., Lyytikäinen, Leo-Pekka, Pahkala, Katja, Raitakari, Olli T., Panoutsopoulou, Kalliope, Zeggini, Eleftheria, Boomsma, Dorret I., Groen-Blokhuis, Maria, Ilonen, Jorma, Franke, Lude, Hirschhorn, Joel N., Pers, Tune H., Liang, Liming, Huang, Jinyan, Hocher, Berthold, Knip, Mikael, Saw, Seang-Mei, Holloway, John W., Melén, Erik, Grant, Struan F.A., Feenstra, Bjarke, Lowe, William L., Widén, Elisabeth, Sergeyev, Elena, Grallert, Harald, Custovic, Adnan, Jacobsson, Bo, Jarvelin, Marjo-Riitta, Atalay, Mustafa, Koppelman, Gerard H., Pennell, Craig E., Niinikoski, Harri, Dedoussis, George V., Mccarthy, Mark I., Frayling, Timothy M., Sunyer, Jordi, Timpson, Nicholas J., Rivadeneira, Fernando, Bønnelykke, Klaus, and Jaddoe, Vincent W.V.

Published
2015
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11. A trans-ancestral meta-analysis of genome-wide association studies reveals loci associated with childhood obesity.

Author

Bradfield, Jonathan P, Vogelezang, Suzanne, Felix, Janine F, Chesi, Alessandra, Helgeland, Øyvind, Horikoshi, Momoko, Karhunen, Ville, Lowry, Estelle, Cousminer, Diana L, Ahluwalia, Tarunveer S, Thiering, Elisabeth, Boh, Eileen Tai-Hui, Zafarmand, Mohammad H, Vilor-Tejedor, Natalia, Wang, Carol A, Joro, Raimo, Chen, Zhanghua, Gauderman, William J, Pitkänen, Niina, and Parra, Esteban J

Published
2019
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12. Consortium-based genome-wide meta-analysis for childhood dental caries traits

Author

Haworth, Simon, primary, Shungin, Dmitry, additional, van der Tas, Justin T, additional, Vucic, Strahinja, additional, Medina-Gomez, Carolina, additional, Yakimov, Victor, additional, Feenstra, Bjarke, additional, Shaffer, John R, additional, Lee, Myoung Keun, additional, Standl, Marie, additional, Thiering, Elisabeth, additional, Wang, Carol, additional, Bønnelykke, Klaus, additional, Waage, Johannes, additional, Jessen, Leon Eyrich, additional, Nørrisgaard, Pia Elisabeth, additional, Joro, Raimo, additional, Seppälä, Ilkka, additional, Raitakari, Olli, additional, Dudding, Tom, additional, Grgic, Olja, additional, Ongkosuwito, Edwin, additional, Vierola, Anu, additional, Eloranta, Aino-Maija, additional, West, Nicola X, additional, Thomas, Steven J, additional, McNeil, Daniel W, additional, Levy, Steven M, additional, Slayton, Rebecca, additional, Nohr, Ellen A, additional, Lehtimäki, Terho, additional, Lakka, Timo, additional, Bisgaard, Hans, additional, Pennell, Craig, additional, Kühnisch, Jan, additional, Marazita, Mary L, additional, Melbye, Mads, additional, Geller, Frank, additional, Rivadeneira, Fernando, additional, Wolvius, Eppo B, additional, Franks, Paul W, additional, Johansson, Ingegerd, additional, and Timpson, Nicholas J, additional

Published
2018
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13. Consortium genome-wide meta-analysis for childhood dental caries traits

Author

Haworth, Simon, primary, Shungin, Dmitry, additional, van der Tas, Justin T, additional, Vucic, Strahinja, additional, Gomez, Carolina Medina, additional, Yakimov, Victor, additional, Feenstra, Bjarke, additional, Shaffer, John R, additional, Lee, Myoung Keun, additional, Standl, Marie, additional, Thiering, Elisabeth, additional, Wang, Carol, additional, Bønnelykke, Klaus, additional, Waage, Johannes, additional, Jessen, Leon Eyrich, additional, Nørrisgaard, Pia Elisabeth, additional, Joro, Raimo, additional, Seppälä, Ilkka, additional, Raitakari, Olli, additional, Dudding, Tom, additional, Grgic, Olja, additional, Ongkosuwito, Edwin, additional, Vierola, Anu, additional, Eloranta, Aino-Maija, additional, West, Nicola X, additional, Thomas, Steven J, additional, McNeil, Daniel W, additional, Levy, Steven M, additional, Slayton, Rebecca, additional, Nohr, Ellen A, additional, Lehtimäki, Terho, additional, Lakka, Timo, additional, Bisgaard, Hans, additional, Pennell, Craig, additional, Kühnisch, Jan, additional, Marazita, Mary L, additional, Melbye, Mads, additional, Geller, Frank, additional, Rivadeneira, Fernando, additional, Wolvius, Eppo B, additional, Franks, Paul W, additional, Johansson, Ingegerd, additional, and Timpson, Nicholas J, additional

Published
2017
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16. A novel common variant in DCST2 is associated with length in early life and height in adulthood

Author

van der Valk, Ralf J P, Kreiner-Møller, Eskil, Kooijman, Marjolein N, Guxens, Mònica, Stergiakouli, Evangelia, Sääf, Annika, Bradfield, Jonathan P, Geller, Frank, Hayes, M Geoffrey, Cousminer, Diana L, Körner, Antje, Thiering, Elisabeth, Curtin, John A, Myhre, Ronny, Huikari, Ville, Joro, Raimo, Kerkhof, Marjan, Warrington, Nicole M, Pitkänen, Niina, Ntalla, Ioanna, Horikoshi, Momoko, Veijola, Riitta, Freathy, Rachel M, Teo, Yik-Ying, Barton, Sheila J, Evans, David M, Kemp, John P, St Pourcain, Beate, Ring, Susan M, Davey Smith, George, Bergström, Anna, Kull, Inger, Hakonarson, Hakon, Mentch, Frank D, Bisgaard, Hans, Chawes, Bo, Stokholm, Jakob, Waage, Johannes, Eriksen, Patrick, Sevelsted, Astrid, Melbye, Mads, van Duijn, Cornelia M, Medina-Gomez, Carolina, Hofman, Albert, de Jongste, Johan C, Taal, H Rob, Uitterlinden, André G, Armstrong, Loren L, Eriksson, Johan, Gehring, Ulrike, Early Genetics and Lifecourse Epidemiology (EAGLE) Consortium, LS IRAS EEPI ME (Milieu epidemiologie), IRAS RATIA2, and Risk Assessment

Abstract

Common genetic variants have been identified for adult height, but not much is known about the genetics of skeletal growth in early life. To identify common genetic variants that influence fetal skeletal growth, we meta-analyzed 22 genome-wide association studies (Stage 1; N = 28 459). We identified seven independent top single nucleotide polymorphisms (SNPs) (P < 1 × 10(-6)) for birth length, of which three were novel and four were in or near loci known to be associated with adult height (LCORL, PTCH1, GPR126 and HMGA2). The three novel SNPs were followed-up in nine replication studies (Stage 2; N = 11 995), with rs905938 in DC-STAMP domain containing 2 (DCST2) genome-wide significantly associated with birth length in a joint analysis (Stages 1 + 2; β = 0.046, SE = 0.008, P = 2.46 × 10(-8), explained variance = 0.05%). Rs905938 was also associated with infant length (N = 28 228; P = 5.54 × 10(-4)) and adult height (N = 127 513; P = 1.45 × 10(-5)). DCST2 is a DC-STAMP-like protein family member and DC-STAMP is an osteoclast cell-fusion regulator. Polygenic scores based on 180 SNPs previously associated with human adult stature explained 0.13% of variance in birth length. The same SNPs explained 2.95% of the variance of infant length. Of the 180 known adult height loci, 11 were genome-wide significantly associated with infant length (SF3B4, LCORL, SPAG17, C6orf173, PTCH1, GDF5, ZNFX1, HHIP, ACAN, HLA locus and HMGA2). This study highlights that common variation in DCST2 influences variation in early growth and adult height.

Published
2015

17. Life-course GWAS approach for total body BMD unveils 16 new BMD loci with some exerting age-specific effects

Author

Medina-Gomez, Carolina, primary, Kemp, John, additional, Chesi, Alessandra, additional, Kreiner-Moller, Eskil, additional, Harris, Tamara, additional, Mook, Dennis, additional, Hatwig, Fernando, additional, Joro, Raimo, additional, Nedeljkovic, Ivana, additional, Evans, Dan, additional, Mullin, Benjamin, additional, Ohlsson, Claes, additional, Styrkarsdottir, Unnur, additional, Karasik, David, additional, McGuigan, Fiona, additional, Kiel, Doug, additional, Uitterlinden, Andre, additional, Tobias, Jon, additional, Evans, Dave, additional, and Rivadeneira, Fernando, additional

Published
2016
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18. Changes in cytokines, leptin, and IGF-1 levels in overtrained athletes during a prolonged recovery phase: A case-control study.

Author

Joro, Raimo, Uusitalo, Arja, DeRuisseau, Keith C., and Atalay, Mustafa

Subjects
*PHYSIOLOGICAL adaptation, *ATHLETES, *CYTOKINES, *EXERCISE physiology, *INTERLEUKINS, *LONGITUDINAL method, *PROBABILITY theory, *SOMATOMEDIN, *TUMOR necrosis factors, *LEPTIN, *COOLDOWN, *OVERTRAINING, *CASE-control method
Abstract

We investigated how cytokines are implicated with overtraining syndrome (OTS) in athletes during a prolonged period of recovery. Plasma IL-6, IL-10, TNF-α, IL-1β, adipokine leptin, and insulin like growth factor-1 (IGF-1) concentrations were measured in overtrained (OA: 5 men, 2 women) and healthy control athletes (CA: 5 men, 5 women) before and after exercise to volitional exhaustion. Measurements were conducted at baseline and after 6 and 12 months. Inflammatory cytokines did not differ between groups at rest. However, resting leptin concentration was lower in OA than CA at every measurement (P < 0.050) but was not affected by acute exercise. Although IL-6 and TNF-α concentrations increased with exercise in both groups (P < 0.050), pro-inflammatory IL-1β concentration increased only in OA (P < 0.050) and anti-inflammatory IL-10 was greater in CA (P < 0.001). In OA, exercise-related IL-6 and TNF-α induction was enhanced during the follow-up (P < 0.050). IGF-1 decreased with exercise in OA (P < 0.050); however, no differences in resting IGF-1 were observed. In conclusion, low leptin level at rest and a pro-inflammatory cytokine response to acute exercise may reflect a chronic maladaptation state in overtrained athletes. In contrast, the accentuation of IL-6 and TNF-α responses to acute exercise seemed to associate with the progression of recovery from overtraining. [ABSTRACT FROM PUBLISHER]

Published
2017
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19. A novel common variant in DCST2 is associated with length in early life and height in adulthood

Author

van der Valk, Ralf J.P., Kreiner-Møller, Eskil, Kooijman, Marjolein N., Guxens, Mònica, Stergiakouli, Evangelia, Sääf, Annika, Bradfield, Jonathan P., Geller, Frank, Hayes, M. Geoffrey, Cousminer, Diana L., Körner, Antje, Thiering, Elisabeth, Curtin, John A., Myhre, Ronny, Huikari, Ville, Joro, Raimo, Kerkhof, Marjan, Warrington, Nicole M., Pitkänen, Niina, Ntalla, Ioanna, Horikoshi, Momoko, Veijola, Riitta, Freathy, Rachel M., Teo, Yik-Ying, Barton, Sheila J., Evans, David M., Kemp, John P., St Pourcain, Beate, Ring, Susan M., Davey Smith, George, Bergström, Anna, Kull, Inger, Hakonarson, Hakon, Mentch, Frank D., Bisgaard, Hans, Chawes, Bo, Stokholm, Jakob, Waage, Johannes, Eriksen, Patrick, Sevelsted, Astrid, Melbye, Mads, van Duijn, Cornelia M., Medina-Gomez, Carolina, Hofman, Albert, de Jongste, Johan C., Taal, H. Rob, Uitterlinden, André G., Armstrong, Loren L., Eriksson, Johan, Palotie, Aarno, Bustamante, Mariona, Estivill, Xavier, Gonzalez, Juan R., Llop, Sabrina, Kiess, Wieland, Mahajan, Anubha, Flexeder, Claudia, Tiesler, Carla M.T., Murray, Clare S., Simpson, Angela, Magnus, Per, Sengpiel, Verena, Hartikainen, Anna-Liisa, Keinanen-Kiukaanniemi, Sirkka, Lewin, Alexandra, Da Silva Couto Alves, Alexessander, Blakemore, Alexandra I., Buxton, Jessica L., Kaakinen, Marika, Rodriguez, Alina, Sebert, Sylvain, Vaarasmaki, Marja, Lakka, Timo, Lindi, Virpi, Gehring, Ulrike, Postma, Dirkje S., Ang, Wei, Newnham, John P., Lyytikäinen, Leo-Pekka, Pahkala, Katja, Raitakari, Olli T., Panoutsopoulou, Kalliope, Zeggini, Eleftheria, Boomsma, Dorret I., Groen-Blokhuis, Maria, Ilonen, Jorma, Franke, Lude, Hirschhorn, Joel N., Pers, Tune H., Liang, Liming, Huang, Jinyan, Hocher, Berthold, Knip, Mikael, Saw, Seang-Mei, Holloway, John W., Melén, Erik, Grant, Struan F.A., Feenstra, Bjarke, Lowe, William L., Widén, Elisabeth, Sergeyev, Elena, Grallert, Harald, Custovic, Adnan, Jacobsson, Bo, Jarvelin, Marjo-Riitta, Atalay, Mustafa, Koppelman, Gerard H., Pennell, Craig E., Niinikoski, Harri, Dedoussis, George V., Mccarthy, Mark I., Frayling, Timothy M., Sunyer, Jordi, Timpson, Nicholas J., Rivadeneira, Fernando, Bønnelykke, Klaus, and Jaddoe, Vincent W.V.

Abstract

Common genetic variants have been identified for adult height, but not much is known about the genetics of skeletal growth in early life. To identify common genetic variants that influence fetal skeletal growth, we meta-analyzed 22 genome-wide association studies (Stage 1; N = 28 459). We identified seven independent top single nucleotide polymorphisms (SNPs) (P < 1 × 10−6) for birth length, of which three were novel and four were in or near loci known to be associated with adult height (LCORL, PTCH1, GPR126 and HMGA2). The three novel SNPs were followed-up in nine replication studies (Stage 2; N = 11 995), with rs905938 in DC-STAMP domain containing 2 (DCST2) genome-wide significantly associated with birth length in a joint analysis (Stages 1 + 2; β = 0.046, SE = 0.008, P = 2.46 × 10−8, explained variance = 0.05%). Rs905938 was also associated with infant length (N = 28 228; P = 5.54 × 10−4) and adult height (N = 127 513; P = 1.45 × 10−5). DCST2 is a DC-STAMP-like protein family member and DC-STAMP is an osteoclast cell-fusion regulator. Polygenic scores based on 180 SNPs previously associated with human adult stature explained 0.13% of variance in birth length. The same SNPs explained 2.95% of the variance of infant length. Of the 180 known adult height loci, 11 were genome-wide significantly associated with infant length (SF3B4, LCORL, SPAG17, C6orf173, PTCH1, GDF5, ZNFX1, HHIP, ACAN, HLA locus and HMGA2). This study highlights that common variation in DCST2 influences variation in early growth and adult height.

Published
2014
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20. Novel loci for childhood body mass index and shared heritability with adult cardiometabolic traits

Author

Vogelezang, Suzanne, Bradfield, Jonathan P., Ahluwalia, Tarunveer S., Curtin, John A., Lakka, Timo A., Grarup, Niels, Scholz, Markus, Van Der Most, Peter J., Monnereau, Claire, Stergiakouli, Evie, Heiskala, Anni, Horikoshi, Momoko, Fedko, Iryna O., Vilor-Tejedor, Natalia, Cousminer, Diana L., Standl, Marie, Wang, Carol A., Viikari, Jorma, Geller, Frank, Íñiguez, Carmen, Pitkänen, Niina, Chesi, Alessandra, Bacelis, Jonas, Yengo, Loic, Torrent, Maties, Ntalla, Ioanna, Helgeland, Øyvind, Selzam, Saskia, Vonk, Judith M., Zafarmand, Mohammed H., Heude, Barbara, Farooqi, Ismaa Sadaf, Alyass, Akram, Beaumont, Robin N., Have, Christian T., Rzehak, Peter, Bilbao, Jose Ramon, Schnurr, Theresia M., Barroso, Inês, Bønnelykke, Klaus, Beilin, Lawrence J., Carstensen, Lisbeth, Charles, Marie-Aline, Chawes, Bo, Clément, Karine, Closa-Monasterolo, Ricardo, Custovic, Adnan, Eriksson, Johan G., Escribano, Joaquin, Groen-Blokhuis, Maria, Grote, Veit, Gruszfeld, Dariusz, Hakonarson, Hakon, Hansen, Torben, Hattersley, Andrew T., Hollensted, Mette, Hottenga, Jouke-Jan, Hyppönen, Elina, Johansson, Stefan, Joro, Raimo, Kähönen, Mika, Karhunen, Ville, Kiess, Wieland, Knight, Bridget A., Koletzko, Berthold, Kühnapfel, Andreas, Landgraf, Kathrin, Langhendries, Jean-Paul, Lehtimäki, Terho, Leinonen, Jaakko T., Li, Aihuali, Lindi, Virpi, Lowry, Estelle, Bustamante, Mariona, Medina-Gomez, Carolina, Melbye, Mads, Michaelsen, Kim F., Morgen, Camilla S., Mori, Trevor A., Nielsen, Tenna R. H., Niinikoski, Harri, Oldehinkel, Albertine J., Pahkala, Katja, Panoutsopoulou, Kalliope, Pedersen, Oluf, Pennell, Craig E., Power, Christine, Reijneveld, Sijmen A., Rivadeneira, Fernando, Simpson, Angela, Sly, Peter D., Stokholm, Jakob, Teo, Kook K., Thiering, Elisabeth, Timpson, Nicholas J., Uitterlinden, André G., Van Beijsterveldt, Catharina E. M., Van Schaik, Barbera D. C., Vaudel, Marc, Verduci, Elvira, Vinding, Rebecca K., Vogel, Mandy, Zeggini, Eleftheria, Sebert, Sylvain, Lind, Mads V., Brown, Christopher D., Santa-Marina, Loreto, Reischl, Eva, Frithioff-Bøjsøe, Christine, Meyre, David, Wheeler, Eleanor, Ong, Ken, Nohr, Ellen A., Vrijkotte, Tanja G. M., Koppelman, Gerard H., Plomin, Robert, Njølstad, Pål R., Dedoussis, George D., Froguel, Philippe, Sørensen, Thorkild I. A., Jacobsson, Bo, Freathy, Rachel M., Zemel, Babette S., Raitakari, Olli, Vrijheid, Martine, Feenstra, Bjarke, Lyytikäinen, Leo-Pekka, Snieder, Harold, Kirsten, Holger, Holt, Patrick G., Heinrich, Joachim, Widén, Elisabeth, Sunyer, Jordi, Boomsma, Dorret I., Järvelin, Marjo-Riitta, Körner, Antje, Davey Smith, George, Holm, Jens-Christian, Atalay, Mustafa, Murray, Clare, Bisgaard, Hans, McCarthy, Mark I., Early Growth Genetics Consortium, Jaddoe, Vincent W. V., Grant, Struan F. A., and Felix, Janine F.

Subjects
2. Zero hunger, Research and analysis methods, Physical sciences, Medicine and health sciences, Biology and life sciences, nutritional and metabolic diseases, FOS: Physical sciences, Research Article
Abstract

The genetic background of childhood body mass index (BMI), and the extent to which the well-known associations of childhood BMI with adult diseases are explained by shared genetic factors, are largely unknown. We performed a genome-wide association study meta-analysis of BMI in 61,111 children aged between 2 and 10 years. Twenty-five independent loci reached genome-wide significance in the combined discovery and replication analyses. Two of these, located near NEDD4L and SLC45A3, have not previously been reported in relation to either childhood or adult BMI. Positive genetic correlations of childhood BMI with birth weight and adult BMI, waist-to-hip ratio, diastolic blood pressure and type 2 diabetes were detected (Rg ranging from 0.11 to 0.76, P-values

21. Novel loci for childhood body mass index and shared heritability with adult cardiometabolic traits

Author

Vogelezang, Suzanne, Bradfield, Jonathan P, Ahluwalia, Tarunveer S, Curtin, John A, Lakka, Timo A, Grarup, Niels, Scholz, Markus, Van Der Most, Peter J, Monnereau, Claire, Stergiakouli, Evie, Heiskala, Anni, Horikoshi, Momoko, Fedko, Iryna O, Vilor-Tejedor, Natalia, Cousminer, Diana L, Standl, Marie, Wang, Carol A, Viikari, Jorma, Geller, Frank, Íñiguez, Carmen, Pitkänen, Niina, Chesi, Alessandra, Bacelis, Jonas, Yengo, Loic, Torrent, Maties, Ntalla, Ioanna, Helgeland, Øyvind, Selzam, Saskia, Vonk, Judith M, Zafarmand, Mohammed H, Heude, Barbara, Farooqi, Ismaa Sadaf, Alyass, Akram, Beaumont, Robin N, Have, Christian T, Rzehak, Peter, Bilbao, Jose Ramon, Schnurr, Theresia M, Barroso, Inês, Bønnelykke, Klaus, Beilin, Lawrence J, Carstensen, Lisbeth, Charles, Marie-Aline, Chawes, Bo, Clément, Karine, Closa-Monasterolo, Ricardo, Custovic, Adnan, Eriksson, Johan G, Escribano, Joaquin, Groen-Blokhuis, Maria, Grote, Veit, Gruszfeld, Dariusz, Hakonarson, Hakon, Hansen, Torben, Hattersley, Andrew T, Hollensted, Mette, Hottenga, Jouke-Jan, Hyppönen, Elina, Johansson, Stefan, Joro, Raimo, Kähönen, Mika, Karhunen, Ville, Kiess, Wieland, Knight, Bridget A, Koletzko, Berthold, Kühnapfel, Andreas, Landgraf, Kathrin, Langhendries, Jean-Paul, Lehtimäki, Terho, Leinonen, Jaakko T, Li, Aihuali, Lindi, Virpi, Lowry, Estelle, Bustamante, Mariona, Medina-Gomez, Carolina, Melbye, Mads, Michaelsen, Kim F, Morgen, Camilla S, Mori, Trevor A, Nielsen, Tenna RH, Niinikoski, Harri, Oldehinkel, Albertine J, Pahkala, Katja, Panoutsopoulou, Kalliope, Pedersen, Oluf, Pennell, Craig E, Power, Christine, Reijneveld, Sijmen A, Rivadeneira, Fernando, Simpson, Angela, Sly, Peter D, Stokholm, Jakob, Teo, Kook K, Thiering, Elisabeth, Timpson, Nicholas J, Uitterlinden, André G, Van Beijsterveldt, Catharina EM, Van Schaik, Barbera DC, Vaudel, Marc, Verduci, Elvira, Vinding, Rebecca K, Vogel, Mandy, Zeggini, Eleftheria, Sebert, Sylvain, Lind, Mads V, Brown, Christopher D, Santa-Marina, Loreto, Reischl, Eva, Frithioff-Bøjsøe, Christine, Meyre, David, Wheeler, Eleanor, Ong, Ken, Nohr, Ellen A, Vrijkotte, Tanja GM, Koppelman, Gerard H, Plomin, Robert, Njølstad, Pål R, Dedoussis, George D, Froguel, Philippe, Sørensen, Thorkild IA, Jacobsson, Bo, Freathy, Rachel M, Zemel, Babette S, Raitakari, Olli, Vrijheid, Martine, Feenstra, Bjarke, Lyytikäinen, Leo-Pekka, Snieder, Harold, Kirsten, Holger, Holt, Patrick G, Heinrich, Joachim, Widén, Elisabeth, Sunyer, Jordi, Boomsma, Dorret I, Järvelin, Marjo-Riitta, Körner, Antje, Davey Smith, George, Holm, Jens-Christian, Atalay, Mustafa, Murray, Clare, Bisgaard, Hans, McCarthy, Mark I, Early Growth Genetics Consortium, Jaddoe, Vincent WV, Grant, Struan FA, and Felix, Janine F

Subjects
2. Zero hunger, Adult, Male, Menarche, Adolescent, Monosaccharide Transport Proteins, Waist-Hip Ratio, Nedd4 Ubiquitin Protein Ligases, nutritional and metabolic diseases, Cardiometabolic Risk Factors, Blood Pressure, Mendelian Randomization Analysis, 3. Good health, Body Mass Index, Diabetes Mellitus, Type 2, Cardiovascular Diseases, Child, Preschool, Humans, Female, Genetic Predisposition to Disease, Child, Genome-Wide Association Study
Abstract

The genetic background of childhood body mass index (BMI), and the extent to which the well-known associations of childhood BMI with adult diseases are explained by shared genetic factors, are largely unknown. We performed a genome-wide association study meta-analysis of BMI in 61,111 children aged between 2 and 10 years. Twenty-five independent loci reached genome-wide significance in the combined discovery and replication analyses. Two of these, located near NEDD4L and SLC45A3, have not previously been reported in relation to either childhood or adult BMI. Positive genetic correlations of childhood BMI with birth weight and adult BMI, waist-to-hip ratio, diastolic blood pressure and type 2 diabetes were detected (Rg ranging from 0.11 to 0.76, P-values

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

Author

Warrington, Nicole M, Beaumont, Robin N, Horikoshi, Momoko, Day, Felix R, Helgeland, Øyvind, Laurin, Charles, Bacelis, Jonas, Peng, Shouneng, Hao, Ke, Feenstra, Bjarke, Wood, Andrew R, Mahajan, Anubha, Tyrrell, Jessica, Robertson, Neil R, Rayner, N William, Qiao, Zhen, Moen, Gunn-Helen, Vaudel, Marc, Marsit, Carmen J, Chen, Jia, Nodzenski, Michael, Schnurr, Theresia M, Zafarmand, Mohammad H, Bradfield, Jonathan P, Grarup, Niels, Kooijman, Marjolein N, Li-Gao, Ruifang, Geller, Frank, Ahluwalia, Tarunveer S, Paternoster, Lavinia, Rueedi, Rico, Huikari, Ville, Hottenga, Jouke-Jan, Lyytikäinen, Leo-Pekka, Cavadino, Alana, Metrustry, Sarah, Cousminer, Diana L, Wu, Ying, Thiering, Elisabeth, Wang, Carol A, Have, Christian T, Vilor-Tejedor, Natalia, Joshi, Peter K, Painter, Jodie N, Ntalla, Ioanna, Myhre, Ronny, Pitkänen, Niina, Van Leeuwen, Elisabeth M, Joro, Raimo, Lagou, Vasiliki, Richmond, Rebecca C, Espinosa, Ana, Barton, Sheila J, Inskip, Hazel M, Holloway, John W, Santa-Marina, Loreto, Estivill, Xavier, Ang, Wei, Marsh, Julie A, Reichetzeder, Christoph, Marullo, Letizia, Hocher, Berthold, Lunetta, Kathryn L, Murabito, Joanne M, Relton, Caroline L, Kogevinas, Manolis, Chatzi, Leda, Allard, Catherine, Bouchard, Luigi, Hivert, Marie-France, Zhang, Ge, Muglia, Louis J, Heikkinen, Jani, 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, Trier, Caecilie, Van Beijsterveldt, Catharina EM, Murcia, Mario, Bustamante, Mariona, Bonas-Guarch, Sílvia, Hougaard, David M, Mercader, Josep M, Linneberg, Allan, Schraut, Katharina E, Lind, Penelope A, Medland, Sarah E, Shields, Beverley M, Knight, Bridget A, Chai, Jin-Fang, Panoutsopoulou, Kalliope, Bartels, Meike, Sánchez, Friman, Stokholm, Jakob, Torrents, David, Vinding, Rebecca K, Willems, Sara M, Atalay, Mustafa, Chawes, Bo L, Kovacs, Peter, Prokopenko, Inga, Tuke, Marcus A, Yaghootkar, Hanieh, Ruth, Katherine S, Jones, Samuel E, Loh, Po-Ru, Murray, Anna, Weedon, Michael N, Tönjes, Anke, Stumvoll, Michael, Michaelsen, Kim F, Eloranta, Aino-Maija, Lakka, Timo A, Van Duijn, Cornelia M, Kiess, Wieland, Körner, Antje, Niinikoski, Harri, Pahkala, Katja, Raitakari, Olli T, Jacobsson, Bo, Zeggini, Eleftheria, Dedoussis, George V, Teo, Yik-Ying, Saw, Seang-Mei, Montgomery, Grant W, Campbell, Harry, Wilson, James F, Vrijkotte, Tanja GM, Vrijheid, Martine, De Geus, Eco JCN, Hayes, M Geoffrey, Kadarmideen, Haja N, Holm, Jens-Christian, Beilin, Lawrence J, Pennell, Craig E, Heinrich, Joachim, Adair, Linda S, Borja, Judith B, Mohlke, Karen L, Eriksson, Johan G, Widén, Elisabeth E, Hattersley, Andrew T, Spector, Tim D, Kähönen, Mika, Viikari, Jorma S, Lehtimäki, Terho, Boomsma, Dorret I, Sebert, Sylvain, Vollenweider, Peter, Sørensen, Thorkild IA, Bisgaard, Hans, Bønnelykke, Klaus, Murray, Jeffrey C, Melbye, Mads, Nohr, Ellen A, Mook-Kanamori, Dennis O, Rivadeneira, Fernando, Hofman, Albert, Felix, Janine F, Jaddoe, Vincent WV, Hansen, Torben, Pisinger, Charlotta, Vaag, Allan A, Pedersen, Oluf, Uitterlinden, André G, Järvelin, Marjo-Riitta, Power, Christine, Hyppönen, Elina, Scholtens, Denise M, Lowe, William L, Davey Smith, George, Timpson, Nicholas J, Morris, Andrew P, Wareham, Nicholas J, Hakonarson, Hakon, Grant, Struan FA, Frayling, Timothy M, Lawlor, Debbie A, Njølstad, Pål R, Johansson, Stefan, Ong, Ken K, McCarthy, Mark I, Perry, John RB, Evans, David M, and Freathy, Rachel M

Subjects
Adult, Male, Heart Diseases, Models, Genetic, Infant, Newborn, Blood Pressure, Polymorphism, Single Nucleotide, Body Height, 3. Good health, Fetal Development, Diabetes Mellitus, Type 2, Metabolic Diseases, Pregnancy, Risk Factors, Birth Weight, Humans, Female, Genetic Predisposition to Disease, Maternal Inheritance, Maternal-Fetal Exchange, Genome-Wide Association Study
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.

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

Author

Standl, Marie, Grarup, Niels, Mercader, Josep M., Nodzenski, Michael, Warrington, Nicole M., Felix, Janine F., Tuke, Marcus A., Hofman, Albert, Mohlke, Karen L., Strachan, David P., Kadarmideen, Haja N., Bonàs-Guarch, Sílvia, Scholtens, Denise M., Panoutsopoulou, Kalliope, Kovacs, Peter, Li-Gao, Ruifang, Langenberg, Claudia, Bønnelykke, Klaus, Morris, Andrew P., Reynolds, Rebecca M., Sørensen, Thorkild I. A., Day, Felix R., Freathy, Rachel M., Schraut, Katharina E., Feenstra, Bjarke, Bisgaard, Hans, Torrents, David, Carstensen, Lisbeth, De Haan, Hugoline G., Newnham, John P., Ruth, Katherine S., Ring, Susan M., Sánchez, Friman, Pisinger, Charlotta, Bustamante, Mariona, Robertson, Neil R., Rahmioglu, Nilufer, Kutalik, Zoltán, Rueedi, Rico, Boomsma, Dorret I., Horikoshi, Momoko, Rosendaal, Frits R., Van Beijsterveldt, Catharina E. M., Campbell, Harry, Mentch, Frank D., Kreiner, Eskil, Stumvoll, Michael, Fonvig, Cilius E., Willems, Sara M., Willemsen, Gonneke, Prokopenko, Inga, Beaumont, Robin N., Wu, Ying, Geller, Frank, Smith, George Davey, Bennett, Amanda J., Pitkänen, Niina, Dedoussis, George V., Vilor-Tejedor, Natalia, Lindi, Virpi, Jones, Samuel E., Trier, Caecilie, Tam, Claudia H. T., Vrijheid, Martine, Pedersen, Oluf, Tyrrell, Jessica, Widén, Elisabeth, Wareham, Nicholas J., Boh, Eileen Tai Hui, Uitterlinden, André G., De Geus, Eco J. C. N., Mahajan, Anubha, Kiess, Wieland, Vaag, Allan A., Wang, Carol A., Ganesh, Santhi K., Eriksson, Johan G., Van Leeuwen, Elisabeth M., Ong, Ken K., Timpson, Nicholas J., Luan, Jian'An, Murcia, Mario, Hottenga, Jouke-Jan, Van Rooij, Frank J. A., Thiering, Elisabeth, Mook-Kanamori, Dennis O., Davies, Eleanor, Van Zuydam, Natalie R., Ntalla, Ioanna, Vollenweider, Peter, Zhao, Jing Hua, Sebert, Sylvain, Hakonarson, Hakon, Walker, Brian R., Appel, Emil V. R., Joshi, Peter K., Tönjes, Anke, Adair, Linda S., Lakka, Timo A., Have, Christian T., Körner, Antje, Nyholt, Dale R., McMahon, George, Jaddoe, Vincent W. V., Tam, Wing Hung, Tiesler, Carla M. T., Teo, Yik-Ying, Atalay, Mustafa, Raitakari, Olli T., Niinikoski, Harri, Paternoster, Lavinia, Melbye, Mads, Rivadeneira, Fernando, Kähönen, Mika, Bradfield, Jonathan P., Beilin, Lawrence J., Hyppönen, Elina, Loh, Po-Ru, Wood, Andrew R., Ma, Ronald C. W., Scott, Robert A., Viikari, Jorma S., Medina-Gomez, Carolina, Pahkala, Katja, Hansen, Torben, Wilson, James F., Zeggini, Eleftheria, Kooijman, Marjolein N., Joro, Raimo, Cousminer, Diana L., Borja, Judith B., Frayling, Timothy M., Järvelin, Marjo-Riitta, Perry, John R. B., Holm, Jens-Christian, Lagou, Vasiliki, MacKenzie, Scott M., Fernandez-Tajes, Juan, Evans, David M., Pennell, Craig E., McCarthy, Mark I., Waage, Johannes, Heinrich, Joachim, Ahluwalia, Tarunveer S., Grant, Struan F. A., Hemani, Gibran, Lawlor, Debbie A., Lehtimäki, Terho, Van Duijn, Cornelia M., Gaulton, Kyle J., Zondervan, Krina T., Lyytikaïnen, Leo-Pekka, Hollegaard, Mads V., Wang, Xu, Lowe, William L., Yaghootkar, Hanieh, Diver, Louise A., Hattersley, Andrew T., Groves, Christopher J., Hougaard, David M., Power, Christine, Marques-Vidal, Pedro, and Saw, Seang-Mei

Subjects
3. Good health
Abstract

Birth weight (BW) is influenced by both foetal and maternal factors and in observational studies is reproducibly associated with future risk of adult metabolic diseases including type 2 diabetes (T2D) and cardiovascular disease1. These lifecourse associations have often been attributed to the impact of an adverse early life environment. We performed a multi-ancestry genome-wide association study (GWAS) meta-analysis of BW in 153,781 individuals, identifying 60 loci where foetal genotype was associated with BW (P

24. Novel loci for childhood body mass index and shared heritability with adult cardiometabolic traits.

Author

Vogelezang S, Bradfield JP, Ahluwalia TS, Curtin JA, Lakka TA, Grarup N, Scholz M, van der Most PJ, Monnereau C, Stergiakouli E, Heiskala A, Horikoshi M, Fedko IO, Vilor-Tejedor N, Cousminer DL, Standl M, Wang CA, Viikari J, Geller F, Íñiguez C, Pitkänen N, Chesi A, Bacelis J, Yengo L, Torrent M, Ntalla I, Helgeland Ø, Selzam S, Vonk JM, Zafarmand MH, Heude B, Farooqi IS, Alyass A, Beaumont RN, Have CT, Rzehak P, Bilbao JR, Schnurr TM, Barroso I, Bønnelykke K, Beilin LJ, Carstensen L, Charles MA, Chawes B, Clément K, Closa-Monasterolo R, Custovic A, Eriksson JG, Escribano J, Groen-Blokhuis M, Grote V, Gruszfeld D, Hakonarson H, Hansen T, Hattersley AT, Hollensted M, Hottenga JJ, Hyppönen E, Johansson S, Joro R, Kähönen M, Karhunen V, Kiess W, Knight BA, Koletzko B, Kühnapfel A, Landgraf K, Langhendries JP, Lehtimäki T, Leinonen JT, Li A, Lindi V, Lowry E, Bustamante M, Medina-Gomez C, Melbye M, Michaelsen KF, Morgen CS, Mori TA, Nielsen TRH, Niinikoski H, Oldehinkel AJ, Pahkala K, Panoutsopoulou K, Pedersen O, Pennell CE, Power C, Reijneveld SA, Rivadeneira F, Simpson A, Sly PD, Stokholm J, Teo KK, Thiering E, Timpson NJ, Uitterlinden AG, van Beijsterveldt CEM, van Schaik BDC, Vaudel M, Verduci E, Vinding RK, Vogel M, Zeggini E, Sebert S, Lind MV, Brown CD, Santa-Marina L, Reischl E, Frithioff-Bøjsøe C, Meyre D, Wheeler E, Ong K, Nohr EA, Vrijkotte TGM, Koppelman GH, Plomin R, Njølstad PR, Dedoussis GD, Froguel P, Sørensen TIA, Jacobsson B, Freathy RM, Zemel BS, Raitakari O, Vrijheid M, Feenstra B, Lyytikäinen LP, Snieder H, Kirsten H, Holt PG, Heinrich J, Widén E, Sunyer J, Boomsma DI, Järvelin MR, Körner A, Davey Smith G, Holm JC, Atalay M, Murray C, Bisgaard H, McCarthy MI, Jaddoe VWV, Grant SFA, and Felix JF

Subjects
Adolescent, Adult, Blood Pressure, Body Mass Index, Cardiometabolic Risk Factors, Cardiovascular Diseases pathology, Child, Child, Preschool, Diabetes Mellitus, Type 2 pathology, Female, Genome-Wide Association Study methods, Humans, Male, Menarche genetics, Mendelian Randomization Analysis, Waist-Hip Ratio, Cardiovascular Diseases genetics, Diabetes Mellitus, Type 2 genetics, Genetic Predisposition to Disease, Monosaccharide Transport Proteins genetics, Nedd4 Ubiquitin Protein Ligases genetics
Abstract

The genetic background of childhood body mass index (BMI), and the extent to which the well-known associations of childhood BMI with adult diseases are explained by shared genetic factors, are largely unknown. We performed a genome-wide association study meta-analysis of BMI in 61,111 children aged between 2 and 10 years. Twenty-five independent loci reached genome-wide significance in the combined discovery and replication analyses. Two of these, located near NEDD4L and SLC45A3, have not previously been reported in relation to either childhood or adult BMI. Positive genetic correlations of childhood BMI with birth weight and adult BMI, waist-to-hip ratio, diastolic blood pressure and type 2 diabetes were detected (Rg ranging from 0.11 to 0.76, P-values <0.002). A negative genetic correlation of childhood BMI with age at menarche was observed. Our results suggest that the biological processes underlying childhood BMI largely, but not completely, overlap with those underlying adult BMI. The well-known observational associations of BMI in childhood with cardio-metabolic diseases in adulthood may reflect partial genetic overlap, but in light of previous evidence, it is also likely that they are explained through phenotypic continuity of BMI from childhood into adulthood., Competing Interests: I have read the journal's policy and the authors of this manuscript have the following competing interests: MMcC: 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. He serves on advisory panels for Pfizer, NovoNordisk, Zoe Global; has received honoraria from Merck, Pfizer, NovoNordisk and Eli Lilly; has stock options in Zoe Global; has received research funding from Abbvie, Astra Zeneca, Boehringer Ingelheim, Eli Lilly, Janssen, Merck, NovoNordisk, Pfizer, Roche, Sanofi Aventis, Servier & Takeda. MS receives funding from Pfizer Inc. for a project not related to this research. IB and spouse own stock in GlaxoSmithKline and Incyte Corp. ZE and CDB currently serve on the editorial board of PLOS Genetics. AC reports personal fees from Novartis, personal fees from Thermo Fisher Scientific, personal fees from Philips, personal fees from Sanofi, personal fees from Stallergenes Greer, outside the submitted work. KC in involved in consultancy for Danone Research, LNC-therapeutic and Confo-therapeutic but no personal funding is received and this activity not linked to the present research.

Published
2020
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