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The path analysis was estimated with the Weighted Least Squares, mean and variance adjusted (WLSMV) estimator, in the Mplus 5.21 software [ 33].

Survival univariate analysis was estimated with the Kaplan-Meier method and differences were tested with a log rank test.

The accuracy of the FunCoup and STRING priors used in the yeast data analysis was estimated with respect to the Yeastract network.

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The results of MTSS1 immunohistochemical analysis were estimated with semi-quantity method.

P-values for these analysis were estimated with 20,000 permutation steps according to the algorithm given in Yu et al [ 30].

The relationship matrix used in the analysis was estimated using genomic data with the "ibs" (option weight =  "freq") function of GenABEL.

In this analysis, an OLS regression was estimated with the same covariates used in the estimation of the propensity score, but with a different dependent variable, walking distance to the nearest hospital.

For genetic analysis, heritability of traits was estimated with a mixed-effects model with genotype as random effect.

Based on haplotype analysis, each individual haplotype-pair was estimated with haplotype frequencies greater than 5%.

For the ML analysis using GARLI, tree construction was estimated with the model GTR+I+g using the mtRev amino acid substitution matrix, for two replicate runs, and termination criteria with setting genthresholdfortopoterm = 20000 (no new significantly better scoring topology found in > 20000 generations).

Support for branches was estimated with bootstrap analysis (n = 1000).

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