Future nutrigenetics: in search of the missing genetic variation

Area of Science:

• Genetics and Genomics
• Nutritional Science
• Complex Trait Analysis

Background:

• Genetic analysis has identified limited variation for complex disorders and nutrition-related traits.
• Missing genetic variation may be conditional, epigenetic, or of low-moderate effect size, evading current screening methods.
• Neural tube defect studies suggest candidate gene analysis can reveal previously undetected genetic variation.

Purpose of the Study:

• To explore the potential of candidate gene analysis in identifying missing genetic variation for complex traits.
• To propose guidelines for selecting candidate genes associated with obesity and related parameters.
• To integrate candidate gene selection into a strategy for analyzing large datasets from whole genome sequencing.

Main Methods:

• Review of genes with known rare and common variations linked to obesity.
• Analysis of evidence from genetic studies on neural tube defects.
• Development of selection criteria for candidate genes relevant to complex traits.

Main Results:

• Candidate gene analysis is an effective method for discovering low-to-moderate effect size genetic variations.
• Guidelines for candidate gene selection can improve the efficiency of genetic studies.
• This approach aids in managing large datasets from whole genome sequencing.

Conclusions:

• Candidate gene analysis is crucial for uncovering missing heritability in complex traits.
• Strategic gene selection enhances the discovery of genetic factors influencing nutrition-related conditions.
• This methodology is vital for future genetic research utilizing whole genome sequencing data.