Presymptomatic risk assessment for chronic non-communicable diseases

TL;DR

This paper introduces the genetic composite index (GCI), a novel genetic risk measure for pre-symptomatic assessment of chronic non-communicable diseases, integrating genetic and environmental data for improved clinical decision-making.

Contribution

It presents a new framework for CNCD risk assessment using GCI, which relies solely on genetic summary statistics and can incorporate future genetic discoveries.

Findings

GCI effectively predicts disease risk in clinical settings.

Combining GCI with environmental factors enhances risk stratification.

GCI is adaptable to new genetic information as technologies advance.

Abstract

The prevalence of common chronic non-communicable diseases (CNCDs) far overshadows the prevalence of both monogenic and infectious diseases combined. All CNCDs, also called complex genetic diseases, have a heritable genetic component that can be used for pre-symptomatic risk assessment. Common single nucleotide polymorphisms (SNPs) that tag risk haplotypes across the genome currently account for a non-trivial portion of the germ-line genetic risk and we will likely continue to identify the remaining missing heritability in the form of rare variants, copy number variants and epigenetic modifications. Here, we describe a novel measure for calculating the lifetime risk of a disease, called the genetic composite index (GCI), and demonstrate its predictive value as a clinical classifier. The GCI only considers summary statistics of the effects of genetic variation and hence does not require the results of large-scale studies simultaneously assessing multiple risk factors. Combining GCI scores with environmental risk information provides an additional tool for clinical decision-making. The GCI can be populated with heritable risk information of any type, and thus represents a framework for CNCD pre-symptomatic risk assessment that can be populated as additional risk information is identified through next-generation technologies.