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GAMLSS-Based Normative Modeling for Biological Phenotypes

This repository provides code and documentation for fitting GAMLSS (Generalized Additive Models for Location, Scale and Shape) models to biological phenotypes using the Sinh-Arcsinh (SHASH) distribution. This method supports robust modeling of non-Gaussian data and computes individualized z-scores for use in downstream normative modeling and stratification analyses.

Overview

The pipeline includes:

  • Model training using the SHASH distribution on healthy control data
  • Z-score calculation for all subjects based on GAMLSS-derived distributional parameters
  • Output writing to .mat files for MATLAB compatibility

Application

The following R packages are required:

  • gamlss
  • R.matlab
  • pracma

Input

  • .mat file: Preprocessed data containing phenotype, age, sex, and diagnosis (a matrix of subjects on rows and columns = groups (healthy control group = column one and coluns 2-x are diagnostic groups) and 1 given to subject with a diagnosis)

Output

  • Output .mat file: Contains z-scores, centile estimates and fitted parameters

Notes

  • Z-scores computed reflect individual deviation from normative predictions after adjusting for age and sex using SHASH distribution parameters.

  • The model is trained using healthy controls only

  • The SHASH distribution enables modeling of skewness and kurtosis, improving fit to real-world phenotype distributions

Citation

If using this method, please cite the original reference for SHASH:

Jones, M. C., & Pewsey, A. (2009). Sinh-arcsinh distributions. Biometrika, 96(4), 761–780. https://doi.org/10.1093/biomet/asp053

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GAMLSS modeling and z-score calculation

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