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School ofSocial and Community Medicine
University ofBRISTOL
Environmental and genetic influences on childhood growth
trajectories
Laura D Howe
School ofSocial and Community Medicine
University ofBRISTOL
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
School ofSocial and Community Medicine
University ofBRISTOL
Heritability of height
80-90%
Strongly predicted by mid-parental height
School ofSocial and Community Medicine
University ofBRISTOL
Environmental influences on height
Barriers to reaching genetic height potential:
Poor child nutrition Child illness Low SEP
School ofSocial and Community Medicine
University ofBRISTOL
Secular trends in height
Batty et al., Econ Hum Biol 2009
School ofSocial and Community Medicine
University ofBRISTOL
Aim
To explore environmental and genetic influences on childhood height growth trajectories in ALSPAC
Comparisons with a cohort from Brazil (Pelotas) where possible
School ofSocial and Community Medicine
University ofBRISTOL
ALSPAC
• Former County of Avon (Bristol)
• >13,000 pregnant women and recruited 1991/1992
• Questionnaires, clinics, links to routine data
School ofSocial and Community Medicine
University ofBRISTOL
Height data in ALSPAC
1. Birth lengths
2. Routine child health records
3. Research clinics
4. Questionnaires
School ofSocial and Community Medicine
University ofBRISTOL
Data birth to ten years
Height measurements
Boys N= 7194 Median = 5IQR = 2-8
Girls N= 6733 Median = 5IQR = 2-8
School ofSocial and Community Medicine
University ofBRISTOL
Analysis strategy
Fractional polynomials
Linear spline random effects models
School ofSocial and Community Medicine
University ofBRISTOL
Height trajectories
4060
8010
012
014
0H
eig
ht (
cm)
0 12 24 36 48 60 72 84 96 108 120Age (months)
Boys Girls
School ofSocial and Community Medicine
University ofBRISTOL
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
School ofSocial and Community Medicine
University ofBRISTOL
Socioeconomicposition and height
Villermé (1829):
French soldiers
Poverty causes short stature
School ofSocial and Community Medicine
University ofBRISTOL
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
School ofSocial and Community Medicine
University ofBRISTOL
Inequalities in heightAge / growth
periodMean growth rates by maternal education p value
Less than O-Level
O-Level A-Level Degree or above
Birth length (cm)
50.55 50.70 50.71 51.02 0.0003
0-3 months (cm/month)
3.84 3.83 3.83 3.82 0.97
3-10 months (cm/month)
1.68 1.69 1.70 1.67 0.57
10-29 months (cm/month)
0.95 0.96 0.96 0.97 0.028
29-120 months
(cm/month)
0.53 0.54 0.54 0.54 <0.0001
Howe et al, JECH, PMID: 20724285
School ofSocial and Community Medicine
University ofBRISTOL
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
School ofSocial and Community Medicine
University ofBRISTOL
Results: SEP inequalities in height trajectories in Pelotas girlsAge / growth
period Mean growth rates by maternal education P value
0-4 years 5-8 years 9+ years
Birth (cm) 47.54 (0.15) 47.81 (0.09) 47.97 (0.09) 0.0400-3 months (cm/month) 3.69 (0.04) 3.77 (0.02) 3.93 (0.02) <0.001
3-12 months (cm/month) 1.55 (0.02) 1.58 (0.01) 1.61 (0.01) 0.002
12-32 months (cm/month) 0.99 (0.01) 1.03 (0.01) 1.06 (0.01) <0.001
32-48 months (cm/month) 0.47 (0.01) 0.47 (0.01) 0.47 (0.01) 0.884
Matijasevich et al., Submitted
School ofSocial and Community Medicine
University ofBRISTOL
Boys
5060
7080
9010
0P
redi
cted
hei
ght (
cm)
0 12 24 36 48Age (months)
Maternal education (years)
Girls
5060
7080
9010
0P
redi
cted
hei
ght (
cm)
0 12 24 36 48Age (months)
0-4
5-8
>= 9
Matijasevich et al., Submitted
School ofSocial and Community Medicine
University ofBRISTOL
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
School ofSocial and Community Medicine
University ofBRISTOL
Main mediator of inequalities in birth length: maternal height
Little attenuation of inequalities in postnatal growth
Matijasevich et al., Submitted
School ofSocial and Community Medicine
University ofBRISTOL
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?
School ofSocial and Community Medicine
University ofBRISTOL
Maternal smoking during pregnancy & child growth
Overall growth rate per month
Maternal smoking during pregnancy (SE)
Partner smoking during pregnancy
(SE)
Maternal – partner
heterogeneity
Birth length 50.74 cm -0.6275 (0.0830) 0.1095 (0.0698) <0.001
Growth 0-3mt 3.83 cm/month 0.0262 (0.0424) -0.0152 (0.0358) 0.46
Growth 3-10mt 1.68 cm/month 0.0476 (0.0196) 0.0063 (0.0166) 0.11
Growth 10-29mt 0.97 cm/month -0.0033 (0.0069) -0.0052 (0.0059) 0.83
Growth 29-120mt 0.53 cm/month -0.0020 (0.0024) -0.0012 (0.0020) 0.80
School ofSocial and Community Medicine
University ofBRISTOL
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?
School ofSocial and Community Medicine
University ofBRISTOL
Genetic influences on heightBirth
length0-3
months3-10
months10-29
months29-120 months
BoysMean birth length, cm (SD) or growth rate, cm per month (SD)
50.65 (1.784)
3.83 (0.204)
1.69 (0.200)
0.96 (0.091)
0.53 (0.037)
Allelic score, cm per month per tall allele (SE)
0.0327(0.0136)
p=0.016
-0.0014 (0.0061)
p=0.819
0.0056 (0.0028)
p=0.050
0.0043 (0.0010)
p=2x10-5
0.0016 (0.0003)
p=5x10-7
GirlsMean birth length, cm (SD) or growth rate, cm per month (SD)
49.64 (1.584)
3.86 (0.161)
1.84 (0.163)
0.90 (0.085)
0.53 (0.037)
Allelic score,cm per month per tall allele (SE)
0.0209 (0.0133)
p=0.117
0.0176 (0.0074)
p=0.017
-0.0011 (0.0020)
p=0.573
0.0046 (0.0010)
p=1x10-6
0.0008 (0.0003)
p=0.022
Paternoster & Howe et al., submitted
School ofSocial and Community Medicine
University ofBRISTOL
Genetic influences on height
Paternoster & Howe et al., submitted
School ofSocial and Community Medicine
University ofBRISTOL
By age 10 Predicted height difference between
individual with 27 and 17 tall alleles (95th and 5th centiles) was: Boys2.97cm (0.50SD)Girls 2.12cm (0.34SD)
The equivalent comparison in the adult paper was:Combined 5cm (0.7SD)
Paternoster & Howe et al., submitted
School ofSocial and Community Medicine
University ofBRISTOL
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
School ofSocial and Community Medicine
University ofBRISTOL
Thank you
Debbie Lawlor Kate Tilling
Lavinia Paternoster Alicia Matijasevich
Marie-Jo Brion, George Davey Smith, Dave Evans, Tim Frayling, Rachel Freathy, Bruna Galobardes, David Gunnell, Sam Leary, Sue Ring, Nic Timpson, Michael Weedon