Correlations between relatives: From Mendelian theory to complete genome sequence

Area of Science:

• Quantitative genetics
• Human genetics
• Genomics

Background:

• R. A. Fisher's 1918 Mendelian model proposed additive genetic effects over loci to explain correlations between relatives.
• Early genetic markers and later single-nucleotide polymorphism (SNP) technology enabled detection of variants with major and minor effects.
• Recent advances allow estimation of additive heritability from large population samples using genotypic correlations.

Purpose of the Study:

• To review the 100-year progression (1918-2018) of analyzing phenotypic correlations between relatives to estimate genetic components of human traits.
• To illustrate the evolution of methods for detecting genetic contributions, from theoretical models to advanced genomic analyses.
• To highlight the use of height as a model trait for understanding genetic architecture.

Main Methods:

• Review of historical and modern quantitative genetic and genomic methodologies.
• Analysis of phenotypic correlations between relatives.
• Genome-Wide Association Studies (GWAS) and analysis of genotypic correlations.
• Utilizing height as an example trait for demonstrating genetic analysis.

Main Results:

• Fisher's model of numerous variants with small effects provides a good approximation for traits like height.
• Phenotypic and genotypic correlations are crucial for mapping causal variants and understanding complex trait genetics.
• Current DNA sequencing data holds potential for estimating total genetic contribution and resolving individual variant effects.

Conclusions:

• The analysis of genetic contributions to human traits has evolved significantly over the past century.
• Genomic technologies have transformed our ability to dissect the genetic architecture of complex traits.
• Future research aims to resolve the biological functions of individual genetic variants contributing to traits.