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Given that we only need to estimate one additional parameter for the within-birth variance-covariance matrix, this result is not unexpected.
Within the war stress variables, personal experience of rape (past rape, rape resulting in pregnancy, rape during pregnancy) accounts for 31% of birth weight variance and eclipses the effect of other war stressors (refugee status, family member killed, past kidnapping, parents or self a result of rape), which can then account for only an additional 4% of the variance in birth weight.
We then tested each of the five random six-gene models in the second data set to assess what fraction of birth weight variance was explained in an independent experiment.
Only two of these six-gene models had positive regression coefficients when applied to the second data set (Adjusted R2 = 0.59, stability 46/48, and R2 = 0.48, stability 44/48, Table 7), indicating that only two of the 1,000 random models generated were robust in explaining birth weight variance.
We fit this model for the 948 SNPs (935 SNPs after LD pruning) with the largest birth date variances corresponding to the 1- π ^ = 0.0211 proportion of SNPs detected to be under strong selection in the BayesCπ analysis of birth date.
Methylation levels at these genes explained 26% of birth weight trait variance in the first data set and 46% of trait variance in the second data set, suggesting that promoter methylation levels are at least as good, and possibly better, at explaining birth weight trait variance than transcript level.
Although this is a significant improvement over the birth weight trait variance explained by any individual gene, it still leaves more than 75% of the trait variance unexplained.
This procedure identified six genes whose methylation levels explained 78% of birth weight trait variance.
In the second approach, we used a machine-learning technique (L1 regularized regression) to identify genes whose methylation level explained a significant fraction of birth weight trait variance.
We also evaluated whether DNA methylation levels of a suite of mechanism-based candidates explains birth weight trait variance better than transcript level of the same genes.
The failure of mechanism-based candidate gene transcript approaches to explain a substantial fraction of birth weight trait variance (e.g. [ 27]) prompted us to consider a more agnostic approach.
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