Genome-wide association analysis identifies three new susceptibility loci for childhood body mass index
| Autor: | Virpi Lindi, Clare S. Murray, Liming Liang, Wieland Kiess, Philippe Froguel, Tarunveer S. Ahluwalia, Hakon Hakonarson, Dorret I. Boomsma, Pitkänen Niina Pitkänen, Romy Gaillard, Mandy Geserick, John A. Curtin, Shana E. McCormack, Niinikoski Harri, Jens-Christian Holm, Vicente Gilsanz, Ville Huikari, Maties Torrent, Nicholas J. Timpson, George Dedoussis, Angela Simpson, Struan F.A. Grant, Klaus Bønnelykke, Anubha Mahajan, George McMahon, Raimo Joro, Christel M. Middeldorp, Johan G. Eriksson, Vilor-Tejedor Natalia Vilor-Tejedor, Gerard H. Koppelman, Frank Geller, Amélie Bonnefond, Hanna Maaria Lakka, Jinyan Huang, Craig E. Pennell, Johannes Waage, Jane Wardle, Torben Hansen, Olli T. Raitakari, John A. Shepherd, Lisbeth Carstensen, Andrea Kelly, Katja Pahkala, Jordi Sunyer, Claire M. A. Haworth, Per Magnus, Juan R. González, Babette S. Zemel, Mads Melbye, Steve Franks, Carla M. T. Tiesler, Roland Pfäffle, Momoko Horikoshi, Susan M. Ring, Adnan Custovic, Claudia Flexeder, Claire Monnereau, Heidi J. Kalkwarf, Janine F. Felix, Julie A. Marsh, Thorkild I. A. Sørensen, André G. Uitterlinden, Mustafa Atalay, Jouke-Jan Hottenga, Mark I. McCarthy, Joel N. Hirschhorn, Niels Grarup, Lude Franke, Diana L. Cousminer, Timo A. Lakka, Robert Plomin, Ronny Myhre, Albert Hofman, Baoshan Ma, Eskil Kreiner-Møller, Jesús Vioque, Vincent W. V. Jaddoe, Hans Bisgaard, Bjarke Feenstra, Sylvain Sebert, Evie Stergiakouli, Eleftheria Zeggini, Joachim Heinrich, Bo Jacobsson, Tune H. Pers, Dirkje S. Postma, Elina Hyppönen, Loic Yengo, Haja N. Kadarmideen, Alana Cavadino, Jonathan P. Bradfield, Elisabeth Thiering, Ralf J. P. van der Valk, George Davey Smith, Alexandra I. F. Blakemore, Christine Power, Marjo-Riitta Järvelin, Wei Ang, Ioanna Ntalla, Sharon E. Oberfield, Fernando Rivadeneira, Rebecca K. Vinding, Alexandra M. Lewin, Mika Kähönen, Verena Sengpiel, Maria M. Groen-Blokhuis, Anna-Liisa Hartikainen, Antje Körner, Oluf Pedersen, Joyce B. J. van Meurs, Alessandra Chesi, Widén Elisabeth Widén, Terho Lehtimäki, Thomas S. Price, Frank D. Mentch, Joan M. Lappe, Leo-Pekka Lyytikäinen |
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| Přispěvatelé: | Groningen Institute for Gastro Intestinal Genetics and Immunology (3GI), Groningen Research Institute for Asthma and COPD (GRIAC), Stem Cell Aging Leukemia and Lymphoma (SALL), Early Growth Genetics (EGG) Consortium, Bone Mineral Density in Childhood Study (BMDCS), Early Genetics and Lifecourse Epidemiology (EAGLE) consortium, Felix, Janine F, Bradfield, Jonathan P, Monnereau, Claire, van der Valk, Ralf JP, Hypponen, Elina, Jaddoe, Vincent WV, Biological Psychology, EMGO+ - Lifestyle, Overweight and Diabetes, Amsterdam Neuroscience - Mood, Anxiety, Psychosis, Stress & Sleep, Erasmus MC other, Epidemiology, Pediatrics, Child and Adolescent Psychiatry / Psychology, Internal Medicine, Public Health |
| Rok vydání: | 2015 |
| Předmět: |
0301 basic medicine
Netherlands Twin Register (NTR) Male ADAM23 Genome-wide association study VARIANTS ENVIRONMENTAL-FACTORS Body Mass Index Child Genetics (clinical) 2. Zero hunger Genetics education.field_of_study Association Studies Articles General Medicine INSIGHTS Child Preschool Female childhood obesity EXPRESSION Adult Risk Adolescent Population body mass index Single-nucleotide polymorphism Biology ta3111 Polymorphism Single Nucleotide Childhood obesity White People 03 medical and health sciences Young Adult children SDG 3 - Good Health and Well-being medicine Humans Obesity Allele education Molecular Biology METAANALYSIS Genetic association FAT DISTRIBUTION ta3121 medicine.disease ta3123 GENE 030104 developmental biology Genetic Loci WEIGHT Body mass index Genome-Wide Association Study |
| Zdroj: | Hum. Mol. Genet. 25, 389-403 (2016) Human Molecular Genetics Human Molecular Genetics, 25(2), 389-403. Oxford University Press Felix, J F, Bradfield, J P, Monnereau, C, van der Valk, R J P, Stergiakouli, E, Chesi, A, Gaillard, R, Feenstra, B, Thiering, E, Kreiner-Møller, E, Blokhuis, M M, Horikoshi, M, Hottenga, J J, Middeldorp, C M, Uitterlinden, A G, Plomin, R, Boomsma, D I, Heinrich, J, Melbye, M, Rivadeneira, F, Hakonarson, H, Ring, S M, Davey Smith, G, Sørensen, T I A, Timpson, N J, Grant, S F A & Jaddoe, V W V 2016, ' Genome-wide association analysis identifies three new susceptibility loci for childhood body mass index ', Human Molecular Genetics, vol. 25, no. 2, pp. 389-403 . https://doi.org/10.1093/hmg/ddv472 Felix, J F, Bradfield, J P, Monnereau, C, Van Der Valk, R J P, Stergiakouli, E, Chesi, A, Gaillard, R, Feenstra, B, Thiering, E, Kreiner-Møller, E, Mahajan, A, Pitk??nen, N, Joro, R, Cavadino, A, Huikari, V, Franks, S, Groen-blokhuis, M M, Cousminer, D L, Marsh, J A, Lehtimäki, T, Curtin, J A, Vioque, J, Ahluwalia, T S, Myhre, R, Price, T S, Vilor-tejedor, N, Yengo, L, Grarup, N, Ntalla, I, Ang, W, Atalay, M, Bisgaard, H, Blakemore, A I, Bonnefond, A, Carstensen, L, Eriksson, J, Flexeder, C, Franke, L, Geller, F, Geserick, M, Hartikainen, A, Haworth, C M A, Hirschhorn, J N, Hofman, A, Holm, J, Horikoshi, M, Hottenga, J J, Huang, J, Kadarmideen, H N, Kähönen, M, Kiess, W, Lakka, H, Lakka, T A, Lewin, A M, Liang, L, Lyytikäinen, L, Ma, B, Magnus, P, Mccormack, S E, Mcmahon, G, Mentch, F D, Middeldorp, C M, Murray, C S, Pahkala, K, Pers, T H, Pfäffle, R, Postma, D S, Power, C, Simpson, A, Sengpiel, V, Tiesler, C M T, Torrent, M, Uitterlinden, A G, Van Meurs, J B, Vinding, R, Waage, J, Wardle, J, Zeggini, E, Zemel, B S, Dedoussis, G V, Pedersen, O, Froguel, P, Sunyer, J, Plomin, R, Jacobsson, B, Hansen, T, Gonzalez, J R, Custovic, A, Raitakari, O T, Pennell, C E, Widøn, E, Boomsma, D I, Koppelman, G H, Sebert, S, Jørvelin, M, Hyppønen, E, Mccarthy, M I, Lindi, V, Harri, N, Kørner, A, Bønnelykke, K, Heinrich, J, Melbye, M, Rivadeneira, F, Hakonarson, H, Ring, S M, Smith, G D, Sørensen, T I A, Timpson, N J, Grant, S F A & Jaddoe, V W V 2015, ' Genome-wide association analysis identifies three new susceptibility loci for childhood body mass index ', Human Molecular Genetics, vol. 25, pp. 389-403 . https://doi.org/10.1093/hmg/ddv472 |
| ISSN: | 1460-2083 0964-6906 |
| Popis: | A large number of genetic loci are associated with adult body mass index. However, the genetics of childhood body mass index are largely unknown. We performed a meta-analysis of genome-wide association studies of childhood body mass index, using sex- and age-adjusted standard deviation scores. We included 35 668 children from 20 studies in the discovery phase and 11 873 children from 13 studies in the replication phase. In total, 15 loci reached genome-wide significance (P-value < 5 × 10−8) in the joint discovery and replication analysis, of which 12 are previously identified loci in or close to ADCY3, GNPDA2, TMEM18, SEC16B, FAIM2, FTO, TFAP2B, TNNI3K, MC4R, GPR61, LMX1B and OLFM4 associated with adult body mass index or childhood obesity. We identified three novel loci: rs13253111 near ELP3, rs8092503 near RAB27B and rs13387838 near ADAM23. Per additional risk allele, body mass index increased 0.04 Standard Deviation Score (SDS) [Standard Error (SE) 0.007], 0.05 SDS (SE 0.008) and 0.14 SDS (SE 0.025), for rs13253111, rs8092503 and rs13387838, respectively. A genetic risk score combining all 15 SNPs showed that each additional average risk allele was associated with a 0.073 SDS (SE 0.011, P-value = 3.12 × 10−10) increase in childhood body mass index in a population of 1955 children. This risk score explained 2% of the variance in childhood body mass index. This study highlights the shared genetic background between childhood and adult body mass index and adds three novel loci. These loci likely represent age-related differences in strength of the associations with body mass index. Refereed/Peer-reviewed |
| Databáze: | OpenAIRE |
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