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GWAS on longitudinal growth traits reveals different genetic factors influencing infant, child, and adult BMI.


ABSTRACT: Early childhood growth patterns are associated with adult health, yet the genetic factors and the developmental stages involved are not fully understood. Here, we combine genome-wide association studies with modeling of longitudinal growth traits to study the genetics of infant and child growth, followed by functional, pathway, genetic correlation, risk score, and colocalization analyses to determine how developmental timings, molecular pathways, and genetic determinants of these traits overlap with those of adult health. We found a robust overlap between the genetics of child and adult body mass index (BMI), with variants associated with adult BMI acting as early as 4 to 6 years old. However, we demonstrated a completely distinct genetic makeup for peak BMI during infancy, influenced by variation at the LEPR/LEPROT locus. These findings suggest that different genetic factors control infant and child BMI. In light of the obesity epidemic, these findings are important to inform the timing and targets of prevention strategies.

SUBMITTER: Couto Alves A 

PROVIDER: S-EPMC6904961 | biostudies-literature | 2019 Sep

REPOSITORIES: biostudies-literature

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GWAS on longitudinal growth traits reveals different genetic factors influencing infant, child, and adult BMI.

Couto Alves Alexessander A   De Silva N Maneka G NMG   Karhunen Ville V   Sovio Ulla U   Das Shikta S   Taal H Rob HR   Warrington Nicole M NM   Lewin Alexandra M AM   Kaakinen Marika M   Cousminer Diana L DL   Thiering Elisabeth E   Timpson Nicholas J NJ   Bond Tom A TA   Lowry Estelle E   Brown Christopher D CD   Estivill Xavier X   Lindi Virpi V   Bradfield Jonathan P JP   Geller Frank F   Speed Doug D   Coin Lachlan J M LJM   Loh Marie M   Barton Sheila J SJ   Beilin Lawrence J LJ   Bisgaard Hans H   Bønnelykke Klaus K   Alili Rohia R   Hatoum Ida J IJ   Schramm Katharina K   Cartwright Rufus R   Charles Marie-Aline MA   Salerno Vincenzo V   Clément Karine K   Claringbould Annique A J AAJ   van Duijn Cornelia M CM   Moltchanova Elena E   Eriksson Johan G JG   Elks Cathy C   Feenstra Bjarke B   Flexeder Claudia C   Franks Stephen S   Frayling Timothy M TM   Freathy Rachel M RM   Elliott Paul P   Widén Elisabeth E   Hakonarson Hakon H   Hattersley Andrew T AT   Rodriguez Alina A   Banterle Marco M   Heinrich Joachim J   Heude Barbara B   Holloway John W JW   Hofman Albert A   Hyppönen Elina E   Inskip Hazel H   Kaplan Lee M LM   Hedman Asa K AK   Läärä Esa E   Prokisch Holger H   Grallert Harald H   Lakka Timo A TA   Lawlor Debbie A DA   Melbye Mads M   Ahluwalia Tarunveer S TS   Marinelli Marcella M   Millwood Iona Y IY   Palmer Lyle J LJ   Pennell Craig E CE   Perry John R JR   Ring Susan M SM   Savolainen Markku J MJ   Rivadeneira Fernando F   Standl Marie M   Sunyer Jordi J   Tiesler Carla M T CMT   Uitterlinden Andre G AG   Schierding William W   O'Sullivan Justin M JM   Prokopenko Inga I   Herzig Karl-Heinz KH   Smith George Davey GD   O'Reilly Paul P   Felix Janine F JF   Buxton Jessica L JL   Blakemore Alexandra I F AIF   Ong Ken K KK   Jaddoe Vincent W V VWV   Grant Struan F A SFA   Sebert Sylvain S   McCarthy Mark I MI   Järvelin Marjo-Riitta MR  

Science advances 20190904 9


Early childhood growth patterns are associated with adult health, yet the genetic factors and the developmental stages involved are not fully understood. Here, we combine genome-wide association studies with modeling of longitudinal growth traits to study the genetics of infant and child growth, followed by functional, pathway, genetic correlation, risk score, and colocalization analyses to determine how developmental timings, molecular pathways, and genetic determinants of these traits overlap  ...[more]

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