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00925njm 22002777a 4500 dc Vogelezang, Suzanne author Bradfield, Jonathan P author Ahluwalia, Tarunveer S author Curtin, John A author Lakka, Timo A author Grarup, Niels author Scholz, Markus author van der Most, Peter J author Monnereau, Claire author Stergiakouli, Evie author Heiskala, Anni author Horikoshi, Momoko author Fedko, Iryna O author Vilor-Tejedor, Natalia author Cousminer, Diana L author Standl, Marie author Wang, Carol A author Viikari, Jorma author Geller, Frank author iniguez, Carmen author Pitkanen, Niina author Chesi, Alessandra author Bacelis, Jonas author Yengo, Loic author Torrent Quetglas, Maties author Ntalla, Ioanna author Helgeland, Øyvind author Selzam, Saskia author Vonk, Judith M author Zafarmand, Mohammed H author Heude, Barbara author Farooqi, Ismaa Sadaf author Alyass, Akram author Beaumont, Robin N author Have, Christian T author Rzehak, Peter author Bilbao, Jose Ramon author Schnurr, Theresia M author Barroso, Ines author Bonnelykke, Klaus author Beilin, Lawrence J author Carstensen, Lisbeth author Charles, Marie-Aline author Chawes, Bo author Clement, Karine author Closa-Monasterolo, Ricardo author Custovic, Adnan author Eriksson, Johan G author Escribano, Joaquin author Groen-Blokhuis, Maria author Grote, Veit author Gruszfeld, Dariusz author Hakonarson, Hakon author Hansen, Torben author Hattersley, Andrew T author Hollensted, Mette author Hottenga, Jouke-Jan author Hyppönen, Elina author Johansson, Stefan author Joro, Raimo author Kähönen, Mika author Karhunen, Ville author Kiess, Wieland author Knight, Bridget A author Koletzko, Berthold author Küehnapfel, Andreas author Landgraf, Kathrin author Langhendries, Jean-Paul author Lehtimäki, Terho author Leinonen, Jaakko T author Li, Aihuali author Lindi, Virpi author Lowry, Estelle author Bustamante, Mariona author Medina-Gomez, Carolina author Melbye, Mads author Michaelsen, Kim F author Morgen, Camilla S author Mori, Trevor A author Nielsen, Tenna RH author Niinikoski, Harri author Oldehinkel, Albertine J author Pahkala, Katja author Panoutsopoulou, Kalliope author Pedersen, Oluf author Pennell, Craig E author Power, Christine author Reijneveld, Sijmen A author Rivadeneira, Fernando author Simpson, Angela author Sly, Peter D author Stokholm, Jakob author Teo, Kook K author Thiering, Elisabeth author Timpson, Nicholas J author Uitterlinden, Andre G author van Beijsterveldt, Catharina E. M author van Schaik, Barbera D. C author Vaudel, Marc author Verduci, Elvira author Vinding, Rebecca K author Vogel, Mandy author Zeggini, Eleftheria author Sebert, Sylvain author Lind, Mads V author Brown, Christopher D author Santa-Marina, Loreto author Reischl, Eva author Frithioff-Bøjsøe, Christine author Meyre, David author Wheeler, Eleanor author Ong, Ken author Nohr, Ellen A author Vrijkotte, Tanja G. M author Koppelman, Gerard H author Plomin, Robert author Njølstad, Pal R author Dedoussis, George D author Froguel, Philippe author Sorensen, Thorkild I. A author Jacobsson, Bo author Freathy, Rachel M author Zemel, Babette S author Raitakari, Olli author Vrijheid, Martine author Feenstra, Bjarke author Lyytikäinen, Leo-Pekka author Snieder, Harold author Kirsten, Holger author Holt, Patrick G author Heinrich, Joachim author Widen, Elisabeth author Sunyer, Jordi author Boomsma, Dorret I author Järvelin, Marjo-Riitta author Köerner, Antje author Davey Smith, George author Holm, Jens-Christian author Atalay, Mustafa author Murray, Clare author Bisgaard, Hans author McCarthy, Mark I author Early Growth Genetics Consortium author Jaddoe, Vincent WV author Grant, Struan FA author Felix, Janine F author 2020-10 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 <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. Author summary Although twin studies have shown that body mass index (BMI) is highly heritable, many common genetic variants involved in the development of BMI have not yet been identified, especially in children. We studied associations of more than 40 million genetic variants with childhood BMI in 61,111 children aged between 2 and 10 years. We identified 25 genetic variants that were associated with childhood BMI. Two of these have not been implicated for BMI previously, located close to the genesNEDD4LandSLC45A3. We also show that the genetic background of childhood BMI overlaps with that of birth weight, adult BMI, waist-to-hip-ratio, diastolic blood pressure, type 2 diabetes, and age at menarche. Our results suggest that the biological processes underlying childhood BMI largely overlap with those underlying adult BMI. However, the overlap is not complete. Additionally, the genetic backgrounds of childhood BMI and other cardio-metabolic phenotypes are overlapping. This may mean that the associations of childhood BMI and later cardio-metabolic outcomes are partially explained by shared genetics, but it could also be explained by the strong association of childhood BMI with adult BMI. Vogelezang S, Bradfield JP, Ahluwalia TS, Curtin JA, Lakka TA, Grarup N, et al. Novel loci for childhood body mass index and shared heritability with adult cardiometabolic traits. PLoS Genet. 2020 Oct;16(10):e1008718. 10.1371/journal.pgen.1008718 1553-7404 PloS Genetics http://hdl.handle.net/20.500.13003/9198 33045005 L2008348102 2-s2.0-85092931223 https://hdl.handle.net/20.500.12105/23028 582197600001 Novel loci for childhood body mass index and shared heritability with adult cardiometabolic traits