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Brief Summary

The "Comorbidities as Quantitative Traits" project introduces an innovative approach to studying the genetics of complex diseases by treating the correlations between comorbid traits as quantitative traits themselves. This study focuses on obesity and its associated morbidities, proposing that the physiological connections between these traits vary from individual to individual in ways that are genetically influenced and biologically relevant. By developing new statistical methods to analyze within-individual trait correlations, the project aims to uncover novel genetic insights into disease mechanisms and improve risk prediction in complex diseases.

Expanded Summary

Background and Objectives

Complex diseases often manifest as a constellation of interrelated phenotypes rather than a single trait. Traditional genetic approaches typically focus on individual traits or their combined effects, potentially missing important biological information contained in the relationships between these traits. This project proposes a novel perspective: treating the correlations between comorbid traits as quantitative traits in their own right.

The primary objectives of this project are:

  1. Demonstrate that within-individual trait correlations vary and are biologically relevant to disease prognosis.
  2. Develop statistical methods to analyze within-individual trait correlations as quantitative traits.
  3. Identify genetic factors influencing these trait correlations.
  4. Explore the biological significance of genes associated with trait correlations.

Conceptual Framework

The project introduces several key concepts:

  1. Within vs. Across Individual Distinction: Emphasizing the importance of distinguishing between correlations observed within individuals over time and those observed across a population at a single time point.
  2. Physiological Correlations: Conceptualizing the relationships between traits within an individual as reflections of underlying physiological connections.
  3. Associative Pleiotropy: Introducing a new type of genetic effect where genes influence the relationship between traits rather than the traits themselves.

Methodology

The study employs a multi-faceted approach: