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

Author

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

Subjects
Genetics, QH426-470
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

Published
2020
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2. Author Correction: Trans-ancestral genome-wide association study of longitudinal pubertal height growth and shared heritability with adult health outcomes

Author

Jonathan P. Bradfeld, Rachel L. Kember, Anna Ulrich, Zhanna Balkhiyarova, Akram Alyass, Izzuddin M. Aris, Joshua A. Bell, K. Alaine Broadaway, Zhanghua Chen, Jin-Fang Chai, Neil M. Davies, Dietmar Fernandez-Orth, Mariona Bustamante, Ruby Fore, Amitavo Ganguli, Anni Heiskala, Jouke-Jan Hottenga, Carmen Íñiguez, Sayuko Kobes, Jaakko Leinonen, Estelle Lowry, Leo-Pekka Lyytikainen, Anubha Mahajan, Niina Pitkänen, Theresia M. Schnurr, Christian Theil Have, David P. Strachan, Elisabeth Thiering, Suzanne Vogelezang, Kaitlin H. Wade, Carol A. Wang, Andrew Wong, Louise Aas Holm, Alessandra Chesi, Catherine Choong, Miguel Cruz, Paul Elliott, Steve Franks, Christine Frithiof-Bøjsøe, W. James Gauderman, Joseph T. Glessner, Vicente Gilsanz, Kendra Griesman, Robert L. Hanson, Marika Kaakinen, Heidi Kalkwarf, Andrea Kelly, Joseph Kindler, Mika Kähönen, Carla Lanca, Joan Lappe, Nanette R. Lee, Shana McCormack, Frank D. Mentch, Jonathan A. Mitchell, Nina Mononen, Harri Niinikoski, Emily Oken, Katja Pahkala, Xueling Sim, Yik-Ying Teo, Leslie J. Baier, Toos van Beijsterveldt, Linda S. Adair, Dorret I. Boomsma, Eco de Geus, Mònica Guxens, Johan G. Eriksson, Janine F. Felix, Frank D. Gilliland, Penn Medicine Biobank, Torben Hansen, Rebecca Hardy, Marie-France Hivert, Jens-Christian Holm, Vincent W. V. Jaddoe, Marjo-Riitta Järvelin, Terho Lehtimäki, David A. Mackey, David Meyre, Karen L. Mohlke, Juha Mykkänen, Sharon Oberfeld, Craig E. Pennell, John R. B. Perry, Olli Raitakari, Fernando Rivadeneira, Seang-Mei Saw, Sylvain Sebert, John A. Shepherd, Marie Standl, Thorkild I. A. Sørensen, Nicholas J. Timpson, Maties Torrent, Gonneke Willemsen, Elina Hypponen, Chris Power, The Early Growth Genetics Consortium, Mark I. McCarthy, Rachel M. Freathy, Elisabeth Widén, Hakon Hakonarson, Inga Prokopenko, Benjamin F. Voight, Babette S. Zemel, Struan F. A. Grant, and Diana L. Cousminer

Subjects
Biology (General), QH301-705.5, Genetics, QH426-470
Published
2024
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3. Trans-ancestral genome-wide association study of longitudinal pubertal height growth and shared heritability with adult health outcomes

Author

Jonathan P. Bradfield, Rachel L. Kember, Anna Ulrich, Zhanna Balkhiyarova, Akram Alyass, Izzuddin M. Aris, Joshua A. Bell, K. Alaine Broadaway, Zhanghua Chen, Jin-Fang Chai, Neil M. Davies, Dietmar Fernandez-Orth, Mariona Bustamante, Ruby Fore, Amitavo Ganguli, Anni Heiskala, Jouke-Jan Hottenga, Carmen Íñiguez, Sayuko Kobes, Jaakko Leinonen, Estelle Lowry, Leo-Pekka Lyytikainen, Anubha Mahajan, Niina Pitkänen, Theresia M. Schnurr, Christian Theil Have, David P. Strachan, Elisabeth Thiering, Suzanne Vogelezang, Kaitlin H. Wade, Carol A. Wang, Andrew Wong, Louise Aas Holm, Alessandra Chesi, Catherine Choong, Miguel Cruz, Paul Elliott, Steve Franks, Christine Frithioff-Bøjsøe, W. James Gauderman, Joseph T. Glessner, Vicente Gilsanz, Kendra Griesman, Robert L. Hanson, Marika Kaakinen, Heidi Kalkwarf, Andrea Kelly, Joseph Kindler, Mika Kähönen, Carla Lanca, Joan Lappe, Nanette R. Lee, Shana McCormack, Frank D. Mentch, Jonathan A. Mitchell, Nina Mononen, Harri Niinikoski, Emily Oken, Katja Pahkala, Xueling Sim, Yik-Ying Teo, Leslie J. Baier, Toos van Beijsterveldt, Linda S. Adair, Dorret I. Boomsma, Eco de Geus, Mònica Guxens, Johan G. Eriksson, Janine F. Felix, Frank D. Gilliland, Penn Medicine Biobank, Torben Hansen, Rebecca Hardy, Marie-France Hivert, Jens-Christian Holm, Vincent W. V. Jaddoe, Marjo-Riitta Järvelin, Terho Lehtimäki, David A. Mackey, David Meyre, Karen L. Mohlke, Juha Mykkänen, Sharon Oberfield, Craig E. Pennell, John R. B. Perry, Olli Raitakari, Fernando Rivadeneira, Seang-Mei Saw, Sylvain Sebert, John A. Shepherd, Marie Standl, Thorkild I. A. Sørensen, Nicholas J. Timpson, Maties Torrent, Gonneke Willemsen, Elina Hypponen, Chris Power, The Early Growth Genetics Consortium, Mark I. McCarthy, Rachel M. Freathy, Elisabeth Widén, Hakon Hakonarson, Inga Prokopenko, Benjamin F. Voight, Babette S. Zemel, Struan F. A. Grant, and Diana L. Cousminer

Subjects
Biology (General), QH301-705.5, Genetics, QH426-470
Abstract

Abstract Background Pubertal growth patterns correlate with future health outcomes. However, the genetic mechanisms mediating growth trajectories remain largely unknown. Here, we modeled longitudinal height growth with Super-Imposition by Translation And Rotation (SITAR) growth curve analysis on ~ 56,000 trans-ancestry samples with repeated height measurements from age 5 years to adulthood. We performed genetic analysis on six phenotypes representing the magnitude, timing, and intensity of the pubertal growth spurt. To investigate the lifelong impact of genetic variants associated with pubertal growth trajectories, we performed genetic correlation analyses and phenome-wide association studies in the Penn Medicine BioBank and the UK Biobank. Results Large-scale growth modeling enables an unprecedented view of adolescent growth across contemporary and 20th-century pediatric cohorts. We identify 26 genome-wide significant loci and leverage trans-ancestry data to perform fine-mapping. Our data reveals genetic relationships between pediatric height growth and health across the life course, with different growth trajectories correlated with different outcomes. For instance, a faster tempo of pubertal growth correlates with higher bone mineral density, HOMA-IR, fasting insulin, type 2 diabetes, and lung cancer, whereas being taller at early puberty, taller across puberty, and having quicker pubertal growth were associated with higher risk for atrial fibrillation. Conclusion We report novel genetic associations with the tempo of pubertal growth and find that genetic determinants of growth are correlated with reproductive, glycemic, respiratory, and cardiac traits in adulthood. These results aid in identifying specific growth trajectories impacting lifelong health and show that there may not be a single “optimal” pubertal growth pattern.

Published
2024
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4. Association between common variation at the FTO locus and changes in body mass index from infancy to late childhood: the complex nature of genetic association through growth and development.

Author

Ulla Sovio, Dennis O Mook-Kanamori, Nicole M Warrington, Robert Lawrence, Laurent Briollais, Colin N A Palmer, Joanne Cecil, Johanna K Sandling, Ann-Christine Syvänen, Marika Kaakinen, Lawrie J Beilin, Iona Y Millwood, Amanda J Bennett, Jaana Laitinen, Anneli Pouta, John Molitor, George Davey Smith, Yoav Ben-Shlomo, Vincent W V Jaddoe, Lyle J Palmer, Craig E Pennell, Tim J Cole, Mark I McCarthy, Marjo-Riitta Järvelin, Nicholas J Timpson, and Early Growth Genetics Consortium

Subjects
Genetics, QH426-470
Abstract

An age-dependent association between variation at the FTO locus and BMI in children has been suggested. We meta-analyzed associations between the FTO locus (rs9939609) and BMI in samples, aged from early infancy to 13 years, from 8 cohorts of European ancestry. We found a positive association between additional minor (A) alleles and BMI from 5.5 years onwards, but an inverse association below age 2.5 years. Modelling median BMI curves for each genotype using the LMS method, we found that carriers of minor alleles showed lower BMI in infancy, earlier adiposity rebound (AR), and higher BMI later in childhood. Differences by allele were consistent with two independent processes: earlier AR equivalent to accelerating developmental age by 2.37% (95% CI 1.87, 2.87, p = 10(-20)) per A allele and a positive age by genotype interaction such that BMI increased faster with age (p = 10(-23)). We also fitted a linear mixed effects model to relate genotype to the BMI curve inflection points adiposity peak (AP) in infancy and AR. Carriage of two minor alleles at rs9939609 was associated with lower BMI at AP (-0.40% (95% CI: -0.74, -0.06), p = 0.02), higher BMI at AR (0.93% (95% CI: 0.22, 1.64), p = 0.01), and earlier AR (-4.72% (-5.81, -3.63), p = 10(-17)), supporting cross-sectional results. Overall, we confirm the expected association between variation at rs9939609 and BMI in childhood, but only after an inverse association between the same variant and BMI in infancy. Patterns are consistent with a shift on the developmental scale, which is reflected in association with the timing of AR rather than just a global increase in BMI. Results provide important information about longitudinal gene effects and about the role of FTO in adiposity. The associated shifts in developmental timing have clinical importance with respect to known relationships between AR and both later-life BMI and metabolic disease risk.

Published
2011
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5. Genetics of early-life head circumference and genetic correlations with neurological, psychiatric and cognitive outcomes

Author

Suzanne Vogelezang, Jonathan P. Bradfield, the Early Growth Genetics Consortium, Struan F. A. Grant, Janine F. Felix, and Vincent W. V. Jaddoe

Subjects
Head circumference, Genome-wide association study, Genetic correlations, Infancy, Internal medicine, RC31-1245, Genetics, QH426-470
Abstract

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
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6. A genome-wide association meta-analysis identifies new childhood obesity loci.

Author

Bradfield, Jonathan P, Taal, H Rob, Timpson, Nicholas J, Scherag, André, Lecoeur, Cecile, Warrington, Nicole M, Hypponen, Elina, Holst, Claus, Valcarcel, Beatriz, Thiering, Elisabeth, Salem, Rany M, Schumacher, Fredrick R, Cousminer, Diana L, Sleiman, Patrick MA, Zhao, Jianhua, Berkowitz, Robert I, Vimaleswaran, Karani S, Jarick, Ivonne, Pennell, Craig E, Evans, David M, St Pourcain, Beate, Berry, Diane J, Mook-Kanamori, Dennis O, Hofman, Albert, Rivadeneira, Fernando, Uitterlinden, André G, van Duijn, Cornelia M, van der Valk, Ralf JP, de Jongste, Johan C, Postma, Dirkje S, Boomsma, Dorret I, Gauderman, W James, Hassanein, Mohamed T, Lindgren, Cecilia M, Mägi, Reedik, Boreham, Colin AG, Neville, Charlotte E, Moreno, Luis A, Elliott, Paul, Pouta, Anneli, Hartikainen, Anna-Liisa, Li, Mingyao, Raitakari, Olli, Lehtimäki, Terho, Eriksson, Johan G, Palotie, Aarno, Dallongeville, Jean, Das, Shikta, Deloukas, Panos, McMahon, George, Ring, Susan M, Kemp, John P, Buxton, Jessica L, Blakemore, Alexandra IF, Bustamante, Mariona, Guxens, Mònica, Hirschhorn, Joel N, Gillman, Matthew W, Kreiner-Møller, Eskil, Bisgaard, Hans, Gilliland, Frank D, Heinrich, Joachim, Wheeler, Eleanor, Barroso, Inês, O'Rahilly, Stephen, Meirhaeghe, Aline, Sørensen, Thorkild IA, Power, Chris, Palmer, Lyle J, Hinney, Anke, Widen, Elisabeth, Farooqi, I Sadaf, McCarthy, Mark I, Froguel, Philippe, Meyre, David, Hebebrand, Johannes, Jarvelin, Marjo-Riitta, Jaddoe, Vincent WV, Smith, George Davey, Hakonarson, Hakon, Grant, Struan FA, and Early Growth Genetics Consortium

Subjects
Early Growth Genetics Consortium, Humans, Obesity, Genetic Predisposition to Disease, Genetic Markers, Body Mass Index, Case-Control Studies, Polymorphism, Single Nucleotide, Adolescent, Adult, Genome-Wide Association Study, Young Adult, Genetic Loci, Polymorphism, Single Nucleotide, Developmental Biology, Biological Sciences, Medical and Health Sciences
Abstract

Multiple genetic variants have been associated with adult obesity and a few with severe obesity in childhood; however, less progress has been made in establishing genetic influences on common early-onset obesity. We performed a North American, Australian and European collaborative meta-analysis of 14 studies consisting of 5,530 cases (≥95th percentile of body mass index (BMI)) and 8,318 controls (

Published
2012

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

Author

Vogelezang, Suzanne, Bradfield, Jonathan P., the Early Growth Genetics Consortium, 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, and Herrala, Sauli

Subjects
GENETIC correlations, GENOME-wide association studies, GENETICS, PHENOTYPES
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. [ABSTRACT FROM AUTHOR]

Published
2022
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8. 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, M-A, 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, J-J, Hyppönen, E, Johansson, S, Joro, R, Kähönen, M, Karhunen, V, Kiess, W, Knight, BA, Koletzko, B, Kühnapfel, A, Landgraf, K, Langhendries, J-P, 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, Peter, 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, L-P, Snieder, H, Kirsten, H, Holt, PG, Heinrich, J, Widén, E, Sunyer, J, Boomsma, DI, Järvelin, M-R, Körner, A, Davey Smith, G, Holm, J-C, Atalay, M, Murray, C, Bisgaard, H, McCarthy, MI, Early Growth Genetics Consortium, Jaddoe, VWV, Grant, SFA, Felix, JF, 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, M-A, 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, J-J, Hyppönen, E, Johansson, S, Joro, R, Kähönen, M, Karhunen, V, Kiess, W, Knight, BA, Koletzko, B, Kühnapfel, A, Landgraf, K, Langhendries, J-P, 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, Peter, 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, L-P, Snieder, H, Kirsten, H, Holt, PG, Heinrich, J, Widén, E, Sunyer, J, Boomsma, DI, Järvelin, M-R, Körner, A, Davey Smith, G, Holm, J-C, Atalay, M, Murray, C, Bisgaard, H, McCarthy, MI, Early Growth Genetics Consortium, Jaddoe, VWV, Grant, SFA, and Felix, JF

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.

Published
2020

10. 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

11. 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

12. Genetic effects on the timing of parturition and links to fetal birth weight

Author

Solé-Navais, Pol, Flatley, Christopher, Steinthorsdottir, Valgerdur, Vaudel, Marc, Jacobsson, Bo, Hypponen, Elina, Early Growth Genetics Consortium, Estonian Biobank Research Team, and Danish Blood Donor Study Genomic Consortium

Subjects
fetal birth weight, timing of parturition, genetic effects
Abstract

Refereed/Peer-reviewed The timing of parturition is crucial for neonatal survival and infant health. Yet, its genetic basis remains largely unresolved. We present a maternal genome-wide meta-analysis of gestational duration (n = 195,555), identifying 22 associated loci (24 independent variants) and an enrichment in genes differentially expressed during labor. A meta-analysis of preterm delivery (18,797 cases, 260,246 controls) revealed six associated loci and large genetic similarities with gestational duration. Analysis of the parental transmitted and nontransmitted alleles (n = 136,833) shows that 15 of the gestational duration genetic variants act through the maternal genome, whereas 7 act both through the maternal and fetal genomes and 2 act only via the fetal genome. Finally, the maternal effects on gestational duration show signs of antagonistic pleiotropy with the fetal effects on birth weight: maternal alleles that increase gestational duration have negative fetal effects on birth weight. The present study provides insights into the genetic effects on the timing of parturition and the complex maternal–fetal relationship between gestational duration and birth weight.

Published
2023

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

Author

Inês Barroso, Peter D. Sly, Jose Ramon Bilbao, Nicholas J. Timpson, Johan G. Eriksson, Maria M. Groen-Blokhuis, Sijmen A. Reijneveld, Dariusz Gruszfeld, George Davey Smith, Christine Power, Eva Reischl, Mandy Vogel, Andrew T. Hattersley, Øyvind Helgeland, Niina Pitkänen, Akram Alyass, Jean-Paul Langhendries, Elina Hyppönen, Kathrin Landgraf, Loreto Santa-Marina, Frank Geller, Christopher D. Brown, Elvira Verduci, Katja Pahkala, Olli T. Raitakari, Joaquin Escribano, Torben Hansen, Hakon Hakonarson, Barbara Heude, Bridget A. Knight, Maties Torrent, Robin N Beaumont, Judith M. Vonk, Estelle Lowry, Patrick G. Holt, Harold Snieder, Carol A. Wang, Mark I. McCarthy, Christine Frithioff-Bøjsøe, Tanja G. M. Vrijkotte, Natalia Vilor-Tejedor, Lisbeth Carstensen, Catharina E. M. van Beijsterveldt, Ville Karhunen, Virpi Lindi, Marjo-Riitta Järvelin, Tarunveer S. Ahluwalia, Jordi Sunyer, Jaakko T. Leinonen, Clare S. Murray, Klaus Bønnelykke, Thorkild I. A. Sørensen, André G. Uitterlinden, Janine F. Felix, John A. Curtin, Mika Kähönen, Jorma Viikari, Leo-Pekka Lyytikäinen, Oluf Pedersen, Carmen Iñiguez, Harri Niinikoski, Wieland Kiess, Kim F. Michaelsen, Evie Stergiakouli, Anni Heiskala, Alessandra Chesi, Craig E. Pennell, Mohammed H Zafarmand, Peter Rzehak, Kook K Teo, Aihuali Li, Marie Standl, Veit Grote, Momoko Horikoshi, Ellen A. Nohr, Eleanor Wheeler, Rachel M. Freathy, Iryna O. Fedko, Gerard H. Koppelman, Elisabeth Widen, Jens-Christian Holm, Raimo Joro, David Meyre, Mustafa Atalay, Theresia M. Schnurr, Camilla Schmidt Morgen, Adnan Custovic, Niels Grarup, Trevor A. Mori, Terho Lehtimäki, Christian Theil Have, Angela Simpson, Mads Melbye, Bjarke Feenstra, Lawrence J. Beilin, Stefan Johansson, Ioanna Ntalla, Martine Vrijheid, Mariona Bustamante, George Dedoussis, Sylvain Sebert, Jonas Bacelis, Carolina Medina-Gomez, Elisabeth Thiering, Ken K. Ong, Eleftheria Zeggini, Berthold Koletzko, Karine Clément, Bo L. Chawes, Mette Hollensted, Babette S. Zemel, Markus Scholz, Holger Kirsten, Antje Körner, Albertine J. Oldehinkel, Barbera D. C. van Schaik, Philippe Froguel, Vincent W. V. Jaddoe, Dorret I. Boomsma, Struan F.A. Grant, Loic Yengo, Jonathan P. Bradfield, Tenna Ruest Haarmark Nielsen, Suzanne Vogelezang, Jakob Stokholm, Pål R. Njølstad, Bo Jacobsson, Marc Vaudel, Peter J. van der Most, Andreas Kühnapfel, Mads Vendelbo Lind, Timo A. Lakka, Saskia Selzam, Robert Plomin, Marie-Aline Charles, Jouke-Jan Hottenga, Kalliope Panoutsopoulou, Fernando Rivadeneira, Rebecca K. Vinding, Hans Bisgaard, I. S. Farooqi, Joachim Heinrich, Diana L. Cousminer, Ricardo Closa-Monasterolo, Claire Monnereau, European Commission, Epidemiology, Erasmus MC other, Pediatrics, Internal Medicine, Epidemiology and Data Science, ACS - Atherosclerosis & ischemic syndromes, APH - Aging & Later Life, APH - Global Health, APH - Health Behaviors & Chronic Diseases, APH - Personalized Medicine, ARD - Amsterdam Reproduction and Development, APH - Methodology, AGEM - Amsterdam Gastroenterology Endocrinology Metabolism, ACS - Amsterdam Cardiovascular Sciences, Public and occupational health, Erasmus University Medical Center [Rotterdam] (Erasmus MC), Children’s Hospital of Philadelphia (CHOP ), Herlev and Gentofte Hospital, Manchester Academic Health Science Centre (MAHSC), University of Manchester [Manchester], University of Kuopio, University of Copenhagen = Københavns Universitet (KU), Universität Leipzig [Leipzig], University Medical Center Groningen [Groningen] (UMCG), University of Bristol [Bristol], Université d'Oulu, The Wellcome Trust Centre for Human Genetics [Oxford], University of Oxford [Oxford], Vrije Universiteit Brussel (VUB), CIBER de Epidemiología y Salud Pública (CIBERESP), Helmholtz-Zentrum München (HZM), University of Newcastle [Australia] (UoN), Turku University Hospital (TYKS), Statens Serum Institut [Copenhagen], Sahlgrenska Academy at University of Gothenburg [Göteborg], Metabolic functional (epi)genomics and molecular mechanisms involved in type 2 diabetes and related diseases - UMR 8199 - UMR 1283 (GI3M), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre National de la Recherche Scientifique (CNRS)-Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP), Queen Mary University of London (QMUL), Norwegian Institute of Public Health [Oslo] (NIPH), King‘s College London, University of Groningen [Groningen], University of Amsterdam [Amsterdam] (UvA), Centre de Recherche Épidémiologie et Statistique Sorbonne Paris Cité (CRESS (U1153 / UMR_A_1125 / UMR_S_1153)), Conservatoire National des Arts et Métiers [CNAM] (CNAM)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), University of Cambridge [UK] (CAM), McMaster University [Hamilton, Ontario], University of Exeter, Ludwig-Maximilians-Universität München (LMU), University of the Basque Country [Bizkaia] (UPV/EHU), The Wellcome Trust Sanger Institute [Cambridge], The University of Western Australia (UWA), Nutrition et obésités: approches systémiques (nutriomics) (UMR-S 1269 INSERM - Sorbonne Université), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Universitat Rovira i Virgili, Imperial College London, University of Helsinki, Vrije Universiteit Amsterdam [Amsterdam] (VU), University College of London [London] (UCL), University of Bergen (UiB), University of Tampere [Finland], University of Oulu, Copenhagen University Hospital, University of Turku, University of Queensland [Brisbane], Haukeland University Hospital, Università degli Studi di Milano-Bicocca [Milano] (UNIMIB), National Institute for Health Research Biomedical Research Centre at Great Ormond Street Hospital for Children NHS Foundation Trust University College London Wellcome 090532106130098381203141212259WT206194United States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Institute of Diabetes & Digestive & Kidney Diseases (NIDDK)U01DK105535National Institute for Health Research (NIHR)NF-SI-0617-10090Netherlands Organization for Health Research and DevelopmentTOP 40-00812-9811010American Diabetes Association1-17-PDF-077Daniel B. Burke Chair for Diabetes Research United States Department of Health & Human ServicesNational Institutes of Health (NIH) - USAR01 HD058886Agencia de Gestio D'Ajuts Universitaris de Recerca Agaur (AGAUR)2017 FI_B 00636Generalitat de Catalunya -Fons Social Europeu European Research Council Advanced Grant META-GROWTH (ERC-2012-AdG) 322605Oak Foundation Fellowship Wellcome TrustEuropean CommissionWT104150098497/Z/12/ZRoyal Society of LondonEuropean CommissionWT104150Wellcome Trust098395/Z/12/ZNatural Resources CanadaCanadian Forest ServiceCanada Research Chairs Finnish Cultural Foundation KNAW Academy Professor Award PAH/6635TARGET Danish Diabetes Academy Copenhagen Graduate School of Health and Medical Sciences Netherlands Organization for Health Research and Development (VIDI) 016.136.361European Research Council (ERC)European Commission648916European Research Council (ERC)European Commission UK Research & Innovation (UKRI)Medical Research Council UK (MRC)European CommissionMRC_MC_UU_12012/5MC_UU_00011/1National Institute for Health Research (NIHR) Botnar Foundation Bernard Wolfe Health Neuroscience Endowment European Community's Seventh Framework Programme (FP7/2007-2013) project Beta-JUDO 279153University of Bristol UK Research & Innovation (UKRI)Medical Research Council UK (MRC)MC_UU_00011/1MC_UU_00011/3French National Agency of Research, F-CRIN/FORCE, Clinicum, Johan Eriksson / Principal Investigator, Department of General Practice and Primary Health Care, Helsinki University Hospital Area, Genomics of Sex Differences, Institute for Molecular Medicine Finland, Centre of Excellence in Complex Disease Genetics, Elisabeth Ingrid Maria Widen / Principal Investigator, Genomic Discoveries and Clinical Translation, University of Copenhagen = Københavns Universitet (UCPH), Universität Leipzig, University of Oxford, Helmholtz Zentrum München = German Research Center for Environmental Health, University of Newcastle [Callaghan, Australia] (UoN), Metabolic functional (epi)genomics and molecular mechanisms involved in type 2 diabetes and related diseases - UMR 8199 - UMR 1283 (EGENODIA (GI3M)), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre National de la Recherche Scientifique (CNRS), Conservatoire National des Arts et Métiers [CNAM] (CNAM), HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), University of the Basque Country/Euskal Herriko Unibertsitatea (UPV/EHU), Nutrition et obésités: approches systémiques (UMR-S 1269) (Nutriomics), Helsingin yliopisto = Helsingfors universitet = University of Helsinki, Università degli Studi di Milano-Bicocca = University of Milano-Bicocca (UNIMIB), Felix, Janine F [0000-0002-9801-5774], Apollo - University of Cambridge Repository, Biological Psychology, APH - Mental Health, Felix, Janine F. [0000-0002-9801-5774], Tampere University, Tampere University Hospital Catchment Area, Department of Clinical Physiology and Nuclear Medicine, Clinical Medicine, Department of Clinical Chemistry, Groningen Research Institute for Asthma and COPD (GRIAC), Public Health Research (PHR), Life Course Epidemiology (LCE), Vogelezang, Suzanne, Bradfield, Jonathan P, Ahluwalia, Tarunveer S, Curtin, John A, Hyppönen, Elina, Felix, JF, and Early Growth Genetics Consortium

Subjects
Male, Genetic-variation, Nedd4 Ubiquitin Protein Ligases, Pooled Analysis, Blood Pressure, 0302 clinical medicine, Human genetics, Mendelian Randomization, Young adult, Child, health care economics and organizations, Body mass index, Adiposity, Genetics & Heredity, 0303 health sciences, Statistics, 1184 Genetics, developmental biology, physiology, Genomics, adulto, 3. Good health, Cardiovascular Diseases, Child, Preschool, Physical Sciences, Menarche, genetic-variation, presión sanguínea, Monosaccharide Transport Proteins, Genetic loci, education, enfermedades cardiovasculares, Prostate-specific Antigen, Genetic correlation, 03 medical and health sciences, SDG 3 - Good Health and Well-being, Diabetes Mellitus, Genetics, Humans, prostate-specific antigen, Statistical Methods, Molecular Biology, Ecology, Evolution, Behavior and Systematics, childhood, 0604 Genetics, [SDV.GEN]Life Sciences [q-bio]/Genetics, Science & Technology, Early Growth Genetics Consortium, Biology and Life Sciences, Computational Biology, nutritional and metabolic diseases, Single nucleotide polymorphisms, Mendelian Randomization Analysis, Biological Tissue, Diabetes Mellitus, Type 2, estudio de asociación genómica completa, genetic factors, mendelian randomization, análisis de la aleatorización mendeliana, proteínas de transporte de monosacáridos, 030217 neurology & neurosurgery, Mathematics, Demography, Developmental Biology, Cardiovascular Risk, Cancer Research, obesity, Physiology, humanos, adolescente, Overweight, QH426-470, Genome-wide association studies, Waist–hip ratio, Mathematical and Statistical Techniques, Medicine and Health Sciences, body mass index (BMI), Genetics of disease, Genetics (clinical), 2. Zero hunger, adiposity, Metaanalysis, Physiological Parameters, Connective Tissue, Female, medicine.symptom, Anatomy, pooled analysis, Life Sciences & Biomedicine, Research Article, Adult, cardiovascular risk, Adolescent, Birth weight, menarquia, Adipose tissue, Biology, 3121 Internal medicine, Research and Analysis Methods, medicine, overweight, Genetic Predisposition to Disease, Obesity, 030304 developmental biology, Waist-Hip Ratio, índice de masa corporal, Body Weight, Cardiometabolic Risk Factors, predisposición genética a la enfermedad, Heritability, Genome Analysis, young-adults, Genome-wide Association, índice cintura-cadera, Young-adults, genome-wide association, 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 nearNEDD4LandSLC45A3, 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 (R(g)ranging from 0.11 to 0.76, P-values, CP received funding from the National Institute for Health Research Biomedical Research Centre at Great Ormond Street Hospital for Children NHS Foundation Trust and University College London. MMcC is a Wellcome Senior Investigator and an NIHR Senior Investigator. MMcC received funding from Wellcome (090532, 106130, 098381, 203141, 212259), NIDDK (U01DK105535), and NIHR (NF-SI-0617-10090). TGMV was supported by ZonMW (TOP 40-00812-9811010). DLC was supported by the American Diabetes Association Grant 1-17-PDF-077. SFAG is supported by the Daniel B. Burke Chair for Diabetes Research and NIH Grant R01 HD058886. NVT is funded by a pre-doctoral grant from the Agencia de Gestio d'Ajuts Universitaris i de Recerca (2017 FI_B 00636), Generalitat de Catalunya -Fons Social Europeu. BK received personal funding from the European Research Council Advanced Grant META-GROWTH (ERC-2012-AdG -no. 322605). BF was supported by an Oak Foundation Fellowship. RMF and RNB are supported by Sir Henry Dale Fellowship (Wellcome Trust and Royal Society grant: WT104150). ATH is supported by a Wellcome Trust Senior Investigator award (grant number 098395/Z/12/Z). DM is supported by a Canada Research Chair. DLC was supported by the American Diabetes Association Grant 1-17-PDF077. JTL was supported by the Finnish Cultural Foundation. DIB received a KNAW Academy Professor Award (PAH/6635). MH received PhD scholarship funding from TARGET (http://target.ku.dk), The Danish Diabetes Academy (http://danishdiabetesacademy.dk) and the Copenhagen Graduate School of Health and Medical Sciences. VWVJ received funding from the Netherlands Organization for Health Research and Development (VIDI 016.136.361) and the European Research Council (ERC-2014-CoG-648916). ISF was supported by the European Research Council, Wellcome Trust (098497/Z/12/Z), Medical Research Council (MRC_MC_UU_12012/5), the NIHR Cambridge Biomedical Research Centre, the Botnar Foundation, the Bernard Wolfe Health Neuroscience Endowment and the European Community's Seventh Framework Programme (FP7/2007-2013) project Beta-JUDO n degrees 279153. IB acknowledges funding from Wellcome (WT206194). ES works in a unit that receives funding from the University of Bristol and the UK Medical Research Council (MC_UU_00011/1, MC_UU_00011/3). GDS works in the Medical Research Council Integrative Epidemiology Unit at the University of Bristol, which is supported by the Medical Research Council (MC_UU_00011/1). KC received funds from the French National Agency of Research, F-CRIN/FORCE. All funding for the studies that provided the underlying data for this manuscript can be found in S1 Text. The funders had no role in study design, data collection and analysis, data interpretation, decision to publish, or preparation of the manuscript.

Published
2020

14. A trans-ancestral meta-analysis of Genome-wide Association Studies reveals loci associated with childhood obesity

Author

Jaakko T. Leinonen, Nicholas J. Timpson, Mohammad Hadi Zafarmand, Mette Hollensted, Anne E. Justice, Robert L. Hanson, Struan F.A. Grant, Frank D. Gilliland, Jesús Peralta-Romero, Diana L. Cousminer, Carol A. Wang, Jens-Christian Holm, Lindsay Fernández-Rhodes, Elina Hyppönen, Marc Vaudel, Marjo-Riitta Järvelin, Amélie Bonnefond, Esteban J. Parra, Robert I. Berkowitz, Koon K. Teo, Adnan Custovic, Christian Theil Have, Mariona Bustamante, Kari E. North, Stefan Johansson, Mustafa Atalay, Christine Frithioff-Bøjsøe, Estela Blanco, Adan Valladares-Salgado, Sylvain Sebert, Suzanne Vogelezang, Yujie Wang, Mark I. McCarthy, Timo A. Lakka, Christine Power, Raimo Joro, Oluf Pedersen, Heather M. Highland, Yik Ying Teo, Zhanghua Chen, Pål R. Njølstad, Momoko Horikoshi, William J. Gauderman, Øyvind Helgeland, Klaus Bønnelykke, Anke Hinney, Natalia Vilor-Tejedor, V. Saroja Voruganti, Niels Grarup, Sayuko Kobes, Shana E. McCormack, Christopher D. Brown, Alessandra Chesi, Nancy F. Butte, Triinu Peters, Miguel Cruz, Johan G. Eriksson, Torben Hansen, Babette S. Zemel, Terho Lehtimäki, Niina Pitkänen, Akram Alyass, Vincent W. V. Jaddoe, Elisabeth Thiering, Jonathan P. Bradfield, Eileen Tai-Hui Boh, Janine F. Felix, Olli T. Raitakari, Philippe Froguel, Fernando Rivadeneira, Leo-Pekka Lyytikäinen, Martine Vrijheid, Ville Karhunen, Mika Kähönen, Marie Standl, Angela Simpson, Seang-Mei Saw, David Meyre, Anthony G. Comuzzie, Mickaël Canouil, Tarunveer S. Ahluwalia, John A. Curtin, Barbera D. C. van Schaik, Johannes Hebebrand, Elisabeth Widen, Tanja G. M. Vrijkotte, Leslie J. Baier, Sheila Gahagan, Joachim Heinrich, Claire Monnereau, Jesús Vioque, Hans Bisgaard, Hakon Hakonarson, Estelle Lowry, Craig E. Pennell, Shelley A. Cole, Thorkild I. A. Sørensen, André G. Uitterlinden, Virpi Lindi, Genomics of Sex Differences, Institute for Molecular Medicine Finland, University of Helsinki, Johan Eriksson / Principal Investigator, Department of General Practice and Primary Health Care, Centre of Excellence in Complex Disease Genetics, Elisabeth Ingrid Maria Widen / Principal Investigator, Genomic Discoveries and Clinical Translation, Epidemiology, Erasmus MC other, Pediatrics, Internal Medicine, Bradfield, Jonathan P., Vogelezang, Suzanne, Felix, Janine F., Chesi, Alessandra, Hyppönen, Elina, Jaddoe, Vincent W.V., Early Growth Genetics Consortium, Epidemiology and Data Science, Public and occupational health, ACS - Atherosclerosis & ischemic syndromes, APH - Aging & Later Life, APH - Global Health, APH - Health Behaviors & Chronic Diseases, APH - Personalized Medicine, ARD - Amsterdam Reproduction and Development, APH - Methodology, and AGEM - Amsterdam Gastroenterology Endocrinology Metabolism

Subjects
Male, obesity, Pediatric Obesity, Medizin, IDENTIFIES 3, Genome-wide association study, VARIANTS, ethnic group, single nucleotide polymorphism, genetics, bayesian analysis, genes, Association Studies Article, Child, Genetics (clinical), 11 Medical and Health Sciences, 2. Zero hunger, Genetics, Genetics & Heredity, child, 0303 health sciences, adult, 030305 genetics & heredity, 1184 Genetics, developmental biology, physiology, Chromosome Mapping, General Medicine, 3. Good health, Female, body mass index procedure, childhood obesity, Life Sciences & Biomedicine, asian, Biochemistry & Molecular Biology, SUSCEPTIBILITY LOCI, DATABASE, Single-nucleotide polymorphism, Locus (genetics), Biology, Polymorphism, Single Nucleotide, Wilms Tumor, Childhood obesity, 03 medical and health sciences, SDG 3 - Good Health and Well-being, Genetic variation, medicine, MANAGEMENT, Humans, Genetic Predisposition to Disease, genome, Molecular Biology, 030304 developmental biology, genome-wide association study, Science & Technology, Early Growth Genetics Consortium, Case-control study, Bayes Theorem, 06 Biological Sciences, medicine.disease, Obesity, MC3R GENE, Genetic Loci, Case-Control Studies, 1182 Biochemistry, cell and molecular biology, Body mass index, Genome-Wide Association Study
Abstract

Although hundreds of genome-wide association studies-implicated loci have been reported for adult obesity-related traits, less is known about the genetics specific for early-onset obesity and with only a few studies conducted in non-European populations to date. Searching for additional genetic variants associated with childhood obesity, we performed a trans-ancestral meta-analysis of 30 studies consisting of up to 13 005 cases (≥95th percentile of body mass index (BMI) achieved 2–18 years old) and 15 599 controls (consistently

Published
2019

15. Genetic variation in the 15q25 nicotinic acetylcholine receptor gene cluster (CHRNA5CHRNA3CHRNB4) interacts with maternal self-reported smoking status during pregnancy to influence birth weight

Author

Ville Huikari, Jessica Tyrrell, Sylvain Sebert, Rachel M. Freathy, Lavinia Paternoster, Marjo-Riitta Järvelin, H. Rob Taal, Catherine Potter, Ellen A. Nohr, Debbie A Lawlor, Alana Cavadino, Mads Melbye, Frank Geller, Susan M. Ring, Rachel Bakker, Caroline L Relton, Marie-Jo Brion, George Davey Smith, Timothy M. Frayling, Andrew T. Hattersley, Verena Sengpiel, Lynn P. Lowe, Graham Watt, Jennifer T. Christie, Bo Jacobsson, Jeffrey C. Murray, Jane W. Y. Ng, Anna-Liisa Hartikainen, Elina Hyppönen, Ronny Myhre, Bjarke Feenstra, Albert Hofman, Vincent W. V. Jaddoe, Thorkild I. A. Sørensen, Alex McConnachie, Craig E. Pennell, Per Magnus, Shah Ebrahim, William L. Lowe, Paul C. D. Johnson, Marika Kaakinen, Chris Power, Naveed Sattar, Epidemiology, Erasmus MC other, Medical Research Council (MRC), Tyrell, Jessica, Huikari, Ville, Christie, Jennifer T, Cavadino, Alana, Bakker, Rachel, Brion, Marie Jo A, Geller, Frank, Paternoster, Lavinia, Myhre, Ronny, Potter, Catherine, Johnson, Paul CD, Ebrahim, Shah, Feenstra, Bjarke, Hartikainen, Anna Liisa, Hattersley, Andrew T, Hofman, Albert, Kaakinen, Marika, Lowe, Lynn P, Magnus, Per, McConnachie, Alex, Melbye, Mads, Ng, Jane WY, Nohr, Ellen A, Power, Chris, Ring, Susan M, Sebert, Sylvain P, Sengpiel, Verena, Taal, H Rob, Watt, Graham CM, Sattar, Naveed, Relton, Caroline L, Jacobsson, Bo, Frayling, Timothy M, Sørensen, Thorkild IA, Murray, Jeffrey C, Lawlor, Debbie A, Pennell, Craig E, Jaddoe, Vincent WV, Hypponen, Elina Tuulikki, Lowe, William L Jr, Jarvelin, Marjo-Riitta, Smith, George Davey, Freathy, Rachel M, and Early Growth Genetics Consortium (EGG)

Subjects
medicine.medical_treatment, VARIANT, Receptors, Nicotinic, 0302 clinical medicine, CHILD, Pregnancy, Birth Weight, 030212 general & internal medicine, 11 Medical and Health Sciences, Genetics (clinical), Genetics & Heredity, RISK, Genetics, 0303 health sciences, education.field_of_study, Obstetrics, CHRNA5, Smoking, Association Studies Articles, WOMEN, General Medicine, 3. Good health, Female, HEALTH, medicine.symptom, Life Sciences & Biomedicine, Biochemistry & Molecular Biology, medicine.medical_specialty, Offspring, Birth weight, Population, Nerve Tissue Proteins, Biology, 03 medical and health sciences, LUNG-CANCER, HYPERGLYCEMIA, Early Growth Genetics (EGG) Consortium, medicine, Humans, Genetic Predisposition to Disease, OUTCOME HAPO, GENOME-WIDE ASSOCIATION, education, Molecular Biology, 030304 developmental biology, Science & Technology, Genetic Variation, Infant, 06 Biological Sciences, medicine.disease, Confidence interval, Low birth weight, COHORT PROFILE, biology.protein, Smoking cessation
Abstract

Maternal smoking during pregnancy is associated with low birth weight. Common variation at rs1051730 is robustly associated with smoking quantity and was recently shown to influence smoking cessation during pregnancy, but its influence on birth weight is not clear. We aimed to investigate the association between this variant and birth weight of term, singleton offspring in a well-powered meta-analysis. We stratified 26 241 European origin study participants by smoking status (women who smoked during pregnancy versus women who did not smoke during pregnancy) and, in each stratum, analysed the association between maternal rs1051730 genotype and offspring birth weight. There was evidence of interaction between genotype and smoking (P 5 0.007). In women who smoked during pregnancy, each additional smoking-related T-allele was associated with a 20 g [95% confidence interval (95% CI): 4-36 g] lower birth weight (P 5 0.014). However, in women who did not smoke during pregnancy, the effect size estimate was 5 g per T-allele (95% CI: 24 to 14 g; P 5 0.268). To conclude, smoking status during pregnancy modifies the association between maternal rs1051730 genotype and offspring birth weight. This strengthens the evidence that smoking during pregnancy is causally related to lower offspring birth weight and suggests that population interventions that effectively reduce smoking in pregnant women would result in a reduced prevalence of low birth weight. © The Author 2012. Published by Oxford University Press. All rights reserved.

Published
2012

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