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Large-Scale Multi-Omics Genome-Wide Association Studies Mo-GWAS: Guidelines for Sample Preparation and Normalization

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Identifying Causal Genotype-Phenotype Relationships for Population-Sampled Parent-Child Trios.

Yushi Tang¹, Irineo Cabreros², John D Storey¹

¹Lewis-Sigler Institute for Integrative Genomics, Princeton University, Princeton, New Jersey, USA.

Genetic Epidemiology

|January 12, 2026

Summary

This summary is machine-generated.

Genetic transmission offers natural randomization for identifying causal genetic loci. New methods like the transmission mean test (TMT) leverage parent-child trio data for causal effect estimation, complementing existing approaches.

Keywords:

causal inference causal linkage genome‐wide associations potential outcomes randomized experiments transmission disequilibrium transmission mean test

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Area of Science:

Genetics
Biostatistics
Causal Inference

Background:

Genetic transmission introduces randomization prior to other causal factors influencing child phenotypes.
Parent-child trio data can be modeled to understand genetic transmission as a source of experimental randomization.

Purpose of the Study:

To develop and validate new statistical methods for identifying causal genetic loci using parent-child trio data.
To model genetic transmission as a source of randomization for causal inference.

Main Methods:

Development of the transmission mean test (TMT) and its unbiased estimator for average causal effect.
Derivation of causal properties of the TMT within the potential outcomes framework.
Proof that the transmission disequilibrium test (TDT) is a complementary case of the TMT for affected-only designs.

Main Results:

The TMT is suitable for arbitrarily distributed traits and randomly sampled trios.
The TDT is appropriate for dichotomous traits and trait-based sampling.
Comparison of transmission-based methods with established genotype-phenotype analyses.

Conclusions:

Transmission-based methods offer powerful tools for causal genetic discovery.
The choice between TMT and TDT depends on trait distribution and study design.
Integrating transmission-based methods with other approaches enhances genotype-phenotype analysis.