Computational protocol: Heritable Influence of DBH on Adrenergic and Renal Function: Twin and Disease Studies

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Protocol publication

[…] Descriptive and inferential statistics were obtained at baseline from the entire study population using generalized estimating equations (GEE) implemented in SAS PROC GENMOD in order to account for intra-family correlations between/among twins, siblings and parents . Tertiles of eGFR by CKD-EPI were classified by 33rd and 67th percentiles, used to compare traits of interest while adjusting for age as a covariate. GEE analysis tested for associations between DBH promoter variants or haplotypes with renal and adrenergic traits. Further inferential statistics through chi2 (or Fisher's Exact test) and logistic regression analysis provided information on distribution of haplotypes between/among ethnic groups and in determining the effect of DBH promoter genotype on eGFR. Univariate analyses through general linear models assessed the effect of DBH promoter haplotypes on eGFR and plasma norepinephrine.In order to maintain the false positive (Type I error) rate at α<0.05 during genetic associations at a single locus, we used the Nyholt's single nucleotide polymorphism spectral decomposition (SNPSpD) correction to determined an experiment-wide significance threshold p-value , available at . Haplotypes were imputed from unphased diploid genotypes on the DBH promoter region using an expectation-maximization algorithm in PLINK (version 1.07, Harvard University; Cambridge, MA), , available at .Heritability (h2) estimates of physiological and adrenergic traits were obtained through a variance component method in Sequential Oligogenic Linkage Analysis Routines (SOLAR) available at . Heritability is estimated by the following equation: h2 = VG/VP, where VG is additive genetic variance and VP is total phenotypic variance. Through this method, a normal distribution in twin (monozygotic and dizygotic) pairs is assumed in order to maximize the likelihood with a mean dependent on traits of interest. Genetic covariance (or pleiotropy) of eGFR with other correlated heritable traits was estimated as ρG in SOLAR, while environmental covariance was estimated as parameter ρE.Analyses were conducted in SAS version 9.1 (Statistical Analysis System; Cary, NC), SPSS (IBM, Chicago, IL), Nyholt's SNPSpD , Purcell's PLINK , or SOLAR . Interested parties should contact the authors for further details on data and statistics in these studies. […]

Pipeline specifications

Software tools PLINK, SOLAR
Application GWAS
Diseases Kidney Diseases, Genetic Diseases, Inborn, Renal Insufficiency
Chemicals Catecholamines, Dopamine, Norepinephrine