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Environmental and genetic influences on childhood growth trajectories

Environmental and genetic influences on childhood growth trajectories. Laura D Howe. Height matters!. Shorter stature is associated with: Increased risk of CVD, cardio-respiratory diseases, diabetes Lower success in careers, interviews, etc Lower reported life satisfaction

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Environmental and genetic influences on childhood growth trajectories

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  1. Environmental and genetic influences on childhood growth trajectories Laura D Howe

  2. Height matters! • Shorter stature is associated with: • Increased risk of CVD, cardio-respiratory diseases, diabetes • Lower success in careers, interviews, etc • Lower reported life satisfaction • Not being able to see the band at gigs • Being missed out of photos

  3. Heritability of height • 80-90% • Strongly predicted by mid-parental height

  4. Environmental influences on height Barriers to reaching genetic height potential: • Poor child nutrition • Child illness • Low SEP

  5. Secular trends in height Batty et al., Econ Hum Biol 2009

  6. Aim • To explore environmental and genetic influences on childhood height growth trajectories in ALSPAC • Comparisons with a cohort from Brazil (Pelotas) where possible

  7. ALSPAC • Former County of Avon (Bristol) • >13,000 pregnant women and recruited 1991/1992 • Questionnaires, clinics, links to routine data

  8. Height data in ALSPAC • Birth lengths • Routine child health records • Research clinics • Questionnaires

  9. Data birth to ten years

  10. Analysis strategy • Fractional polynomials • Linear spline random effects models

  11. Height trajectories

  12. Methods: Influences on growth trajectories • Fit indicators into multilevel models;interaction with intercept and each growth period • Socioeconomic position: maternal education • Maternal smoking during pregnancy: yes/no (and partner smoking for comparison) • Genetics: score of 20 ‘tall’ alleles

  13. Socioeconomicposition and height Villermé (1829): French soldiers Poverty causes short stature

  14. Socioeconomic position and height • What is already known? • Low SEP = shorter height • Socioeconomic differential may be narrowing as countries develop • What is less well understood? • Social patterning of postnatal growth • When inequality emerges • Changes over time & economic development

  15. Inequalities in height Howe et al, JECH, PMID: 20724285

  16. Inequalities in height in Pelotas Pelotas cohort • ~4,000 births in 2004 • Pelotas, South Brazil • Height trajectories modelled as in ALSPAC • Inequality in trajectories • Mediating factors

  17. Results: SEP inequalities in height trajectories in Pelotas girls Matijasevich et al., Submitted

  18. Matijasevich et al., Submitted

  19. Mediators of height inequalities • Maternal educMediator Child height • Potential mediators considered: family income, marital status, maternal age, parity, skin colour, maternal height, smoking during pregnancy, gestational age, breast feeding Matijasevich et al., Submitted

  20. Main mediator of inequalities in birth length: maternal height • Little attenuation of inequalities in postnatal growth Matijasevich et al., Submitted

  21. Smoking during pregnancy and height • What is already known? • Causal association with birth length • What is less well understood? • Does the height differential persist? • Associations with postnatal growth?

  22. Maternal smoking during pregnancy & child growth

  23. Genes influencing height • What is already known? • GWAS on adult height:- 180 SNPs explain ~10% variation - 20 SNPs explain ~3% variation • Infancy is a period of canalisation • What is less well understood? • At what age do SNPs identified in adulthood begin to affect growth?

  24. Genetic influences on height Paternoster & Howe et al., submitted

  25. Genetic influences on height Paternoster & Howe et al., submitted

  26. By age 10 • Predicted height difference between individual with 27 and 17 tall alleles (95th and 5th centiles) was: • Boys 2.97cm (0.50SD) • Girls 2.12cm (0.34SD) • The equivalent comparison in the adult paper was: • Combined 5cm (0.7SD) Paternoster & Howe et al., submitted

  27. Conclusions • Height inequality: ~ persists in UK, but is less than LMICs ~ due to in utero factors in UK (maternal height) ~ childhood factors also important in Brazil • Smoking during pregnancy affects birth length but not postnatal growth • SNPs identified in GWAS affect birth length and early childhood growth

  28. Thank you • Debbie Lawlor • Kate Tilling • Lavinia Paternoster • Alicia Matijasevich • Marie-Jo Brion, George Davey Smith, Dave Evans, Tim Frayling, Rachel Freathy, BrunaGalobardes, David Gunnell, Sam Leary, Sue Ring, Nic Timpson, Michael Weedon

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