Novel loci for childhood body mass index and shared heritability with adult cardiometabolic traits
Zemel BS; Iniguez C; Pedersen O; Koletzko B; Escribano J; Monnereau C; Uitterlinden AG; Bisgaard H; Atalay M; Froguel P; Curtin JA; Chesi A; Sly PD; Zeggini E; Heude B; Geller F; Freathy RM; Pennell CE; Horikoshi M; Viikari J; Grote V; Yengo L; Lyytikainen LP; Kuhnapfel A; Korner A; Holm JC; Hakonarson H; Verduci E; Gruszfeld D; Reischl E; Teo KK; Lehtimaki T; Bilbao JR; Bacelis J; Rivadeneira F; Beaumont RN; Reijneveld SA; Johansson S; Vonk JM; Lakka TA; Jarvelin MR; Morgen CS; Timpson NJ; Schnurr TM; Plomin R; Kirsten H; Eriksson JG; Ahluwalia TS; Thiering E; Pahkala K; van der Most PJ; Felix JF; Grarup N; Farooqi IS; Standl M; Simpson A; Groen-Blokhuis M; Bustamante M; Hattersley AT; Barroso I; Njolstad PR; Medina-Gomez C; Sebert S; Charles MA; Hottenga JJ; Lindi V; Raitakari O; Melbye M; Brown CD; Stergiakouli E; Vrijheid M; van Beijsterveldt CEM; Bradfield JP; Boomsma DI; Sunyer J; Zafarmand MH; Vilor-Tejedor N; Hypponen E; Scholz M; Vogel M; Jaddoe VWV; Holt PG; Heinrich J; Landgraf K; Closa-Monasterolo R; Custovic A; Dedoussis GD; Li AHL; Rzehak P; Hansen T; Helgeland O; Lind MV; Vaudel M; Cousminer DL; Snieder H; Alyass A; Joro R; Vrijkotte TGM; Grant SFA; Ntalla I; van Schaik BDC; Meyre D; Lowry E; Michaelsen KF; Hollensted M; Have CT; Stokholm J; Smith GD; Heiskala A; Koppelman GH; Selzam S; Kiess W; McCarthy MI; Knight BA; Beilin LJ; Nohr EA; Jacobsson B; Wheeler E; Panoutsopoulou K; Clement K; Nielsen TRH; Carstensen L; Feenstra B; Niinikoski H; Karhunen V; Sorensen TIA; Frithioff-Bojsoe C; Wang CRA; Chawes B; Bonnelykke K; Kahonen M; Torrent M; Langhendries JP; Vogelezang S; Fedko IO; Leinonen JT; Vinding RK; Power C; Ong K; Mori TA; Widen E; Murray C; Santa-Marina L; Pitkanen N; Oldehinkel AJ
Novel loci for childhood body mass index and shared heritability with adult cardiometabolic traits
Zemel BS
Iniguez C
Pedersen O
Koletzko B
Escribano J
Monnereau C
Uitterlinden AG
Bisgaard H
Atalay M
Froguel P
Curtin JA
Chesi A
Sly PD
Zeggini E
Heude B
Geller F
Freathy RM
Pennell CE
Horikoshi M
Viikari J
Grote V
Yengo L
Lyytikainen LP
Kuhnapfel A
Korner A
Holm JC
Hakonarson H
Verduci E
Gruszfeld D
Reischl E
Teo KK
Lehtimaki T
Bilbao JR
Bacelis J
Rivadeneira F
Beaumont RN
Reijneveld SA
Johansson S
Vonk JM
Lakka TA
Jarvelin MR
Morgen CS
Timpson NJ
Schnurr TM
Plomin R
Kirsten H
Eriksson JG
Ahluwalia TS
Thiering E
Pahkala K
van der Most PJ
Felix JF
Grarup N
Farooqi IS
Standl M
Simpson A
Groen-Blokhuis M
Bustamante M
Hattersley AT
Barroso I
Njolstad PR
Medina-Gomez C
Sebert S
Charles MA
Hottenga JJ
Lindi V
Raitakari O
Melbye M
Brown CD
Stergiakouli E
Vrijheid M
van Beijsterveldt CEM
Bradfield JP
Boomsma DI
Sunyer J
Zafarmand MH
Vilor-Tejedor N
Hypponen E
Scholz M
Vogel M
Jaddoe VWV
Holt PG
Heinrich J
Landgraf K
Closa-Monasterolo R
Custovic A
Dedoussis GD
Li AHL
Rzehak P
Hansen T
Helgeland O
Lind MV
Vaudel M
Cousminer DL
Snieder H
Alyass A
Joro R
Vrijkotte TGM
Grant SFA
Ntalla I
van Schaik BDC
Meyre D
Lowry E
Michaelsen KF
Hollensted M
Have CT
Stokholm J
Smith GD
Heiskala A
Koppelman GH
Selzam S
Kiess W
McCarthy MI
Knight BA
Beilin LJ
Nohr EA
Jacobsson B
Wheeler E
Panoutsopoulou K
Clement K
Nielsen TRH
Carstensen L
Feenstra B
Niinikoski H
Karhunen V
Sorensen TIA
Frithioff-Bojsoe C
Wang CRA
Chawes B
Bonnelykke K
Kahonen M
Torrent M
Langhendries JP
Vogelezang S
Fedko IO
Leinonen JT
Vinding RK
Power C
Ong K
Mori TA
Widen E
Murray C
Santa-Marina L
Pitkanen N
Oldehinkel AJ
PUBLIC LIBRARY SCIENCE
Julkaisun pysyvä osoite on:
https://urn.fi/URN:NBN:fi-fe2021042822036
https://urn.fi/URN:NBN:fi-fe2021042822036
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-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.
Kokoelmat
- Rinnakkaistallenteet [19207]