A1 Refereed original research article in a scientific journal
Novel loci for childhood body mass index and shared heritability with adult cardiometabolic traits
Authors: 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 CRA, Viikari J, Geller F, Iniguez C, Pitkanen N, Chesi A, Bacelis J, Yengo L, Torrent M, Ntalla I, Helgeland O, Selzam S, Vonk JM, Zafarmand MH, Heude B, Farooqi IS, Alyass A, Beaumont RN, Have CT, Rzehak P, Bilbao JR, Schnurr TM, Barroso I, Bonnelykke K, Beilin LJ, Carstensen L, Charles MA, Chawes B, Clement 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, Hypponen E, Johansson S, Joro R, Kahonen M, Karhunen V, Kiess W, Knight BA, Koletzko B, Kuhnapfel A, Landgraf K, Langhendries JP, Lehtimaki T, Leinonen JT, Li AHL, 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-Bojsoe C, Meyre D, Wheeler E, Ong K, Nohr EA, Vrijkotte TGM, Koppelman GH, Plomin R, Njolstad PR, Dedoussis GD, Froguel P, Sorensen TIA, Jacobsson B, Freathy RM, Zemel BS, Raitakari O, Vrijheid M, Feenstra B, Lyytikainen LP, Snieder H, Kirsten H, Holt PG, Heinrich J, Widen E, Sunyer J, Boomsma DI, Jarvelin MR, Korner A, Smith GD, Holm JC, Atalay M, Murray C, Bisgaard H, McCarthy MI, Jaddoe VWV, Grant SFA, Felix JF
Publisher: PUBLIC LIBRARY SCIENCE
Publication year: 2020
Journal: PLoS Genetics
Journal name in source: PLOS GENETICS
Journal acronym: PLOS GENET
Article number: ARTN e1008718
Volume: 16
Issue: 10
Number of pages: 26
ISSN: 1553-7404
eISSN: 1553-7404
DOI: https://doi.org/10.1371/journal.pgen.1008718
Web address : https://doi.org/10.1371/journal.pgen.1008718
Self-archived copy’s web address: https://research.utu.fi/converis/portal/detail/Publication/50891583
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.
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