Causal relationships are represented by one headed arrows. Two headed arrows represents correlational relationships. Observed variables and latent variables are shown in squares and circles, …
Effect sizes are parameterized using the path coefficients β and γ. Power was calculated assuming sample sizes approximating the number of white European individuals in the UK Biobank with …
Path coefficients representing postnatal or prenatal maternal genetic effects, paternal genetic effects (βp) and offspring genetic effects (βo) were fixed to 0.1. The covariance between maternal and …
Maternal genotype proxies a perinatal exposure of interest and is used as an instrumental variable to estimate the causal effect of the perinatal exposure on the offspring outcome. The pathway of …
Observed variables and latent variables are shown in squares and circles respectively. Causal relationships are represented by one headed arrows. Two headed arrows represents correlational …
Power was calculated using sample sizes approximating the number of white European individuals in the UK Biobank reporting their own educational attainment (1000 biological trios, 4000 biological …
An SEM which did not correctly model this relationship was fit to the data. Power was calculated using simulated data with 1000 biological trios, 4000 biological mother-offspring pairs, 1800 …
An SEM which did not correctly model this relationship was fit to the data. Power was calculated using simulated data with 1000 biological trios, 4000 biological mother-offspring pairs, 1800 …
An SEM which did not correctly model this relationship was fit to the data. Power was calculated using simulated data with 1000 biological trios, 4000 biological mother-offspring pairs, 1800 …
An SEM which did not correctly model this relationship was fit to the data. Power was calculated using simulated data with 1000 biological trios, 4000 biological mother-offspring pairs, 1800 …
An SEM which modelled this relationship correctly was fit to the data. Power was calculated using simulated data with 1000 biological trios, 4000 biological mother-offspring pairs, 1800 biological …
An SEM which modelled this relationship correctly was fit to the data. Power was calculated using simulated data with 1000 biological trios, 4000 biological mother-offspring pairs, 1800 biological …
An SEM which modelled this relationship correctly was fit to the data. Power was calculated using simulated data with 1000 biological trios, 4000 biological mother-offspring pairs, 1800 biological …
An SEM which modelled this relationship correctly was fit to the data. Power was calculated using simulated data with 1000 biological trios, 4000 biological mother-offspring pairs, 1800 biological …
Power was calculated using simulated data assuming 1000 biological parent-offspring trios, 4000 biological mother-offspring pairs, 1800 biological father-offspring pairs, 300,000 singletons from …
Unweighed PRS | Weighted PRS | |||||
---|---|---|---|---|---|---|
Estimate | Std Error | P-value | Estimate | Std Error | P-value | |
Offspring effect | –0.008 | 0.004 | 0.058 | –0.173 | 0.115 | 0.132 |
Prenatal maternal effect | 0.035 | 0.013 | 0.006 | 0.893 | 0.383 | 0.020 |
Postnatal maternal effect | –0.017 | 0.011 | 0.130 | –0.419 | 0.335 | 0.211 |
Postnatal paternal effect | 0.003 | 0.005 | 0.588 | 0.048 | 0.151 | 0.751 |
PRS: polygenic risk score constructed using 20 SNPs showing maternal effects on birth weight from Warrington et al., 2019; Std Error: standard error.
Full sample | ||||||
---|---|---|---|---|---|---|
Unweighted PRS | Weighted PRS | |||||
Estimate | Std Error | p-value | Estimate | Std Error | p-value | |
Offspring effect | 0.026 | 0.005 | 3.18 × 10 -7 | 2.474 | 0.485 | 3.40 × 10 -7 |
Prenatal maternal effect | 0.027 | 0.011 | 0.013 | 1.722 | 0.703 | 0.014 |
Postnatal maternal effect | –0.006 | 0.008 | 0.484 | –0.288 | 0.514 | 0.575 |
Postnatal paternal effect | 0.018 | 0.007 | 0.006 | 1.233 | 0.678 | 0.069 |
Excluding adopted individuals with breastfeeding information | ||||||
Unweighted PRS | Weighted PRS | |||||
Estimate | Std Error | p-value | Estimate | Std Error | p-value | |
Offspring effect | 0.025 | 0.005 | 5.52 × 10–7 | 2.441 | 0.372 | 5.15 × 10–11 |
Prenatal maternal effect | 0.017 | 0.012 | 0.140 | 0.909 | 0.705 | 0.197 |
Postnatal maternal effect | 0.004 | 0.009 | 0.682 | 0.549 | 0.595 | 0.357 |
Postnatal paternal effect | 0.019 | 0.007 | 0.005 | 1.273 | 0.552 | 0.021 |
PRS: polygenic risk score constructed using 1,267 SNPs from Lee et al., 2018; Std Error: standard error.
Effect | matrix | Estimate | Std.Error | P-value |
---|---|---|---|---|
GRS | V | 25.317 | 0.190 | 0.000 |
Fetal effect | B_FY | 0.000 | 0.002 | 0.997 |
Postnatal maternal effect | B_MY | 0.007 | 0.004 | 0.113 |
Paternal effect | B_PY | -0.001 | 0.003 | 0.697 |
Prenatal maternal effect | G_MY | 0.003 | 0.005 | 0.586 |
e1 | E1 | 0.206 | 0.001 | 0.000 |
e2 | E2 | 0.179 | 0.005 | 0.000 |
rho | R | -0.045 | 0.369 | 0.907 |
Adopted individuals who knew their breastfeeding status | Adopted individuals who did not know their breastfeeding status | |
---|---|---|
Years of education (mean (SD)) | 13.97 (4.98) | 13.15 (5.00) |
Birthweight (kg; mean (SD)) | 3.30 (0.43) | 3.34 (0.42) |
Effect | matrix | Adopted individuals with age<60 removed (N_G5=2756) | Adopted individuals with age>=60 removed (N_G5=2422) | ||||
---|---|---|---|---|---|---|---|
Estimate | Std.Error | P-value | Estimate | Std.Error | P-value | ||
GRS | V | 571.885 | 4.747 | 0.000 | 571.943 | 5.006 | 0.000 |
Fetal effect | B_FY | 0.026 | 0.005 | 0.000 | 0.025 | 0.005 | 0.000 |
Postnatal maternal effect | B_MY | -0.019 | 0.009 | 0.046 | 0.007 | 0.0100 | 0.482 |
Paternal effect | B_PY | 0.018 | 0.007 | 0.008 | 0.019 | 0.007 | 0.004 |
Prenatal maternal effect | G_MY | 0.039 | 0.011 | 0.001 | 0.014 | 0.012 | 0.235 |
e1 | E1 | 23.897 | 0.119 | 0.000 | 23.870 | 0.126 | 0.000 |
e2 | E2 | 21.544 | 0.857 | 0.000 | 24.335 | 0.727 | 0.000 |
rho | R | 58.208 | 9.397 | 0.000 | 58.262 | 9.956 | 0.000 |
SNPs used to construct unweighted polygenic scores of educational attainment.
SNPs used to construct unweighted polygenic scores of educational attainment.
Comparison of power estimated from asymptotic calculations and simulations using varying sizes of prenatal maternal genetic effects (γm), paternal genetic effects (βp) or offspring genetic effects (βo) with sample sizes approximating the number of individuals in UK Biobank with educational attainment information.
1000 biological parent-offspring trios, 4000 biological mother-offspring pairs, 1800 biological father-offspring pairs, 300,000 singletons, 6000 adopted individuals, and 50 biological mother-adopted offspring pairs. Covariance between parental genotypes was fixed at 0.
Comparison of power to detect pre-natal (γm) and post-natal (βm) maternal genetic effects estimated from asymptotic calculations and simulations using varying sample size for each of the 7 family structures and the remaining family structures approximating the number of individuals in the UK Biobank with educational attainment data.
1000 biological parent-offspring trios, 4000 biological mother-offspring pairs, 1800 biological father-offspring pairs, 300,000 singletons, 6000 adopted individuals, and 50 biological mother-adopted offspring pairs.
Path coefficients representing postnatal or prenatal maternal genetic effects, paternal genetic effects (βp) and offspring genetic effects (βo) were fixed to 0.1. Covariance between parental genotypes was fixed to 0.
Sensitivity analysis for the modelling of educational attainment in the UK Biobank using SNPs from the Okbay et al., 2016.
Some limitations/assumptions of our Structural Equation Model (SEM) and its application to the UK Biobank.
Source Code File. R scripts that fit Structural Equation Modelling to partition maternal genetic effects into pre- and postnatal effects on offspring phenotypes.
Adoption_SEM.R.