Genetic architecture of early childhood growth phenotypes gives insights into their link with later obesity

Silva, N. Maneka G. De; Sebért, Sylvain; Alves, Alexessander Couto; Sovio, Ulla; Das, Shikta; Taal, Rob; Warrington, Nicole M.; Lewin, Arie Y.; Kaakinen, Marika; Cousminer, Diana L.; Thiering, Elisabeth; Timpson, Nicholas J.; Karhunen, Ville; Bond, Tom A; Estivill, Xavier; Lindi, Virpi; Bradfield, Jonathan P.; Geller, Frank; Coin, Lachlan; Loh, Marie; Barton, Sheila J.; Beilin, Lawrence J.; Bisgaard, Hans; Bønnelykke, Klaus; Alili, Rohia; Hatoum, Ida J.; Schramm, Katharina; Cartwright, Rufus; Charles, Marie‐Aline; Salerno, Vincenzo; Clément, Karine; Duijn, Cornelia M. van; Moltchanova, Elena; Eriksson, Johan G.; Elks, Cathy E.; Feenstra, Bjarke; Flexeder, Claudia; Frayling, Timothy M.; Freathy, Rachel M.; Elliott, Paul; Widén, Elisabeth; Hákonarson, Hákon; Hattersley, Andrew T.; Banterle, Marco; Heinrich, Joachim; Heude, Barbara; Holloway, John W.; Hofman, Albert; Hyppönen, Elina; Inskip, Hazel; Kaplan, Lee M.; Hedman, Åsa K.; Läärä, Esa; Prokisch, Holger; Grallert, Harald; Lakka, Timo A.; Lawlor, Debbie A; Melbye, Mads; Ahluwalia, Tarunveer S.; Marinelli, M.; Millwood, Iona Y.; Palmer, Lyle J.; Pennell, Craig E.; Perry, John; Ring, Susan M.; Savolainen, Markku J.; Stefánsson, Kári; Þorleifsson, Guðmar; Rivadeneira, Fernando; Standl, Marie; Sunyer, Jordi; Tiesler, Carla M. T.; Uitterlinden, André G.; Prokopenko, Inga; Herzig, Karl‐Heinz; Smith, George Davey; O’Reilly, Paul; Felix, Janine F.; Buxton, Jessica L.; Blakemore, Alexandra I. F.; Ong, Ken K.; Grant, Struan F.A.; Jaddoe, Vincent W.V.; McCarthy, Mark; Järvelin, Marjo‐Riitta

doi:10.1101/150516

Cited by 3 publications

(3 citation statements)

References 81 publications

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“…In fact, they are not in LD with any marker associated with adult diseases, and might thus promote healthy weight gain during infancy, a notion further supported at the genome level by LD score regression. This result is further supported by a recent independent study 34 suggesting that SNPs in the LEPR/LEPROT locus are associated with BMI at the adiposity peak.…”

supporting

confidence: 83%

Genome-wide association study reveals a dynamic role of common genetic variation in infant and early childhood growth

Helgeland

Vaudel

Júlíusson

et al. 2018

Preprint

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supporting

confidence: 83%

Genome-wide association study reveals a dynamic role of common genetic variation in infant and early childhood growth

Helgeland

Vaudel

Júlíusson

et al. 2018

Preprint

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“…We are planning to generalize our study to these new GRS definitions in the near future. Also, our GRS definition is mainly based on SNPs found associated with BMI in adults and could be extended to include genetic variants more specific to children, taking advantage on recent GWAS discoveries [33][34][35].…”

Section: Plos Geneticsmentioning

confidence: 99%

Exclusive breastfeeding can attenuate body-mass-index increase among genetically susceptible children: A longitudinal study from the ALSPAC cohort

Lye

Dennis

et al. 2020

PLoS Genet

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Recent discoveries from large-scale genome-wide association studies (GWASs) explain a larger proportion of the genetic variability to BMI and obesity. The genetic risk associated with BMI and obesity can be assessed by an obesity-specific genetic risk score (GRS) constructed from genome-wide significant genetic variants. The aim of our study is to examine whether the duration and exclusivity of breastfeeding can attenuate BMI increase during childhood and adolescence due to genetic risks. A total sample of 5,266 children (2,690 boys and 2,576 girls) from the Avon Longitudinal Study of Parents and Children (ALSPAC) was used for the analysis. We evaluated the role of breastfeeding (exclusivity and duration) in modulating BMI increase attributed to the GRS from birth to 18 years of age. The GRS was composed of 69 variants associated with adult BMI and 25 non-overlapping SNPs associated with pediatric BMI. In the high genetic susceptible group (upper GRS quartile), exclusive breastfeeding (EBF) to 5 months reduces BMI by 1.14 kg/m 2 (95% CI, 0.37 to 1.91, p = 0.0037) in 18-year-old boys, which compensates a 3.9-decile GRS increase. In 18-year-old girls, EBF to 5 months decreases BMI by 1.53 kg/m 2 (95% CI, 0.76 to 2.29, p<0.0001), which compensates a 7.0-decile GRS increase. EBF acts early in life by delaying the age at adiposity peak and at adiposity rebound. EBF to 3 months or non-exclusive breastfeeding was associated with a significantly diminished impact on reducing BMI growth during childhood. EBF influences early life growth and development and thus may play a critical role in preventing overweight and obesity among children at high-risk due to genetic factors.

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“…Some very rare mutations are responsible for severe obesity syndrome in humans, 24 and more frequent variants have been associated with BMI variability and obesity in children and adolescents 23,25 . However, the association between individual LEPR variants and the evolution of child BMI has been investigated in few studies and has been suggested to vary according to age 26,27 . We hypothesized that cord blood leptin level and carriage of the rare G allele of a common LEPR variant, the rs9436303 single‐nucleotide polymorphism (SNP), can affect, independently or in interaction, early postnatal growth and later adiposity trajectories.…”

Section: Introductionmentioning

confidence: 99%

Cord blood leptin level and a common variant of its receptor as determinants of the BMI trajectory: The EDEN mother–child cohort

et al. 2022

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Summary Background Cord blood leptin is an indicator of neonatal fat mass and could shape postnatal adiposity trajectories. Investigating genetic polymorphisms of the leptin receptor gene (LEPR) could help understand the mechanisms involved. Objectives We aimed to investigate the association of cord blood leptin level and the LEPR rs9436303 polymorphism, with body mass index (BMI) at adiposity peak (AP) and age at adiposity rebound (AR). Methods In the EDEN cohort, BMI at AP and age at AR were estimated with polynomial mixed models, for 1713 and 1415 children, respectively. Multivariable linear regression models allowed for examining the associations of cord blood leptin level and LEPR rs9436303 genotype with BMI at AP and age at AR adjusted for potential confounders including birth size groups. We also tested interactions between cord blood leptin level and rs9436303 genotype. Results Increased leptin level was associated with reduced BMI at AP and early age at AR (comparing the highest quintile of leptin level to the others). Rs9436303 G‐allele carriage was associated with increased BMI at AP and later age at AR but did not modulate the association with leptin level. Conclusion These results illustrate the role of early life body composition and the intrauterine environment in the programming of adiposity in childhood.

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Genetic architecture of early childhood growth phenotypes gives insights into their link with later obesity

Cited by 3 publications

References 81 publications

Genome-wide association study reveals a dynamic role of common genetic variation in infant and early childhood growth

Genome-wide association study reveals a dynamic role of common genetic variation in infant and early childhood growth

Exclusive breastfeeding can attenuate body-mass-index increase among genetically susceptible children: A longitudinal study from the ALSPAC cohort

Cord blood leptin level and a common variant of its receptor as determinants of the BMI trajectory: The EDEN mother–child cohort

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