Novel loci for childhood body mass index and shared heritability with adult cardiometabolic traits
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; Eriksson, Johan G.; Hyppönen, Elina; Kähönen, Mika; Lehtimäki, Terho; Lyytikäinen, Leo Pekka; Leinonen, Jaakko (2020)
2020
PLoS Genetics
e1008718
Julkaisun pysyvä osoite on
https://urn.fi/URN:NBN:fi:tuni-202012048518
https://urn.fi/URN:NBN:fi:tuni-202012048518
Kuvaus
Peer reviewed
Tiivistelmä
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-valuesAuthor 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.
Kokoelmat
- TUNICRIS-julkaisut [23813]