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Novel loci for childhood body mass index and shared heritability with adult cardiometabolic traits.

ABSTRACT: 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 near NEDD4L and SLC45A3, 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 (Rg 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.

SUBMITTER: Vogelezang S

PROVIDER: S-EPMC7581004 | biostudies-literature | 2020 Oct

REPOSITORIES: biostudies-literature

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Novel loci for childhood body mass index and shared heritability with adult cardiometabolic traits.

Vogelezang Suzanne S Bradfield Jonathan P JP Ahluwalia Tarunveer S TS Curtin John A JA Lakka Timo A TA Grarup Niels N Scholz Markus M van der Most Peter J PJ Monnereau Claire C Stergiakouli Evie E Heiskala Anni A Horikoshi Momoko M Fedko Iryna O IO Vilor-Tejedor Natalia N Cousminer Diana L DL Standl Marie M Wang Carol A CA Viikari Jorma J Geller Frank F Íñiguez Carmen C Pitkänen Niina N Chesi Alessandra A Bacelis Jonas J Yengo Loic L Torrent Maties M Ntalla Ioanna I Helgeland Øyvind Ø Selzam Saskia S Vonk Judith M JM Zafarmand Mohammed H MH Heude Barbara B Farooqi Ismaa Sadaf IS Alyass Akram A Beaumont Robin N RN Have Christian T CT Rzehak Peter P Bilbao Jose Ramon JR Schnurr Theresia M TM Barroso Inês I Bønnelykke Klaus K Beilin Lawrence J LJ Carstensen Lisbeth L Charles Marie-Aline MA Chawes Bo B Clément Karine K Closa-Monasterolo Ricardo R Custovic Adnan A Eriksson Johan G JG Escribano Joaquin J Groen-Blokhuis Maria M Grote Veit V Gruszfeld Dariusz D Hakonarson Hakon H Hansen Torben T Hattersley Andrew T AT Hollensted Mette M Hottenga Jouke-Jan JJ Hyppönen Elina E Johansson Stefan S Joro Raimo R Kähönen Mika M Karhunen Ville V Kiess Wieland W Knight Bridget A BA Koletzko Berthold B Kühnapfel Andreas A Landgraf Kathrin K Langhendries Jean-Paul JP Lehtimäki Terho T Leinonen Jaakko T JT Li Aihuali A Lindi Virpi V Lowry Estelle E Bustamante Mariona M Medina-Gomez Carolina C Melbye Mads M Michaelsen Kim F KF Morgen Camilla S CS Mori Trevor A TA Nielsen Tenna R H TRH Niinikoski Harri H Oldehinkel Albertine J AJ Pahkala Katja K Panoutsopoulou Kalliope K Pedersen Oluf O Pennell Craig E CE Power Christine C Reijneveld Sijmen A SA Rivadeneira Fernando F Simpson Angela A Sly Peter D PD Stokholm Jakob J Teo Kook K KK Thiering Elisabeth E Timpson Nicholas J NJ Uitterlinden André G AG van Beijsterveldt Catharina E M CEM van Schaik Barbera D C BDC Vaudel Marc M Verduci Elvira E Vinding Rebecca K RK Vogel Mandy M Zeggini Eleftheria E Sebert Sylvain S Lind Mads V MV Brown Christopher D CD Santa-Marina Loreto L Reischl Eva E Frithioff-Bøjsøe Christine C Meyre David D Wheeler Eleanor E Ong Ken K Nohr Ellen A EA Vrijkotte Tanja G M TGM Koppelman Gerard H GH Plomin Robert R Njølstad Pål R PR Dedoussis George D GD Froguel Philippe P Sørensen Thorkild I A TIA Jacobsson Bo B Freathy Rachel M RM Zemel Babette S BS Raitakari Olli O Vrijheid Martine M Feenstra Bjarke B Lyytikäinen Leo-Pekka LP Snieder Harold H Kirsten Holger H Holt Patrick G PG Heinrich Joachim J Widén Elisabeth E Sunyer Jordi J Boomsma Dorret I DI Järvelin Marjo-Riitta MR Körner Antje A Davey Smith George G Holm Jens-Christian JC Atalay Mustafa M Murray Clare C Bisgaard Hans H McCarthy Mark I MI Jaddoe Vincent W V VWV Grant Struan F A SFA Felix Janine F JF

PLoS genetics 20201012 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 near NEDD4L and SLC45A3, have not previo ...[more]

PMID: 33045005

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Novel loci for childhood body mass index and shared heritability with adult cardiometabolic traits.

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Novel loci for childhood body mass index and shared heritability with adult cardiometabolic traits.

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