Genetics of human body size and shape: complex segregation analysis

Area of Science:

• Human genetics
• Anthropometry
• Quantitative genetics

Background:

• Understanding the genetic architecture of human quantitative traits is crucial.
• Mixed heritability models allow for the simultaneous estimation of major gene, polygenic, and environmental effects.
• Anthropometric traits offer a valuable model for studying complex genetic influences.

Purpose of the Study:

• To investigate the genetic components of anthropometric variation using a mixed heritability model.
• To analyze genetic effects on principal components derived from anthropometric data in two distinct ethnic groups.
• To differentiate the contributions of major genes and polygenes to trait variation.

Main Methods:

• Principal Components Analysis (PCA) was applied to ~20 anthropometric traits in Mexican and Ashkenazi Jewish families.
• A mixed inheritance model, implemented in the POINTER program, was used to assess genetic effects.
• Genetic hypotheses were tested for the first few principal components (PCs), particularly PC1 representing general size.

Main Results:

• A significant genetic component was found for all factor scores across both samples.
• In the Mexican sample, PC1 and PC2 showed significant contributions from both major genes (codominant) and polygenes.
• For other PCs, major gene effects were rejected, with polygenes accounting for >50% of variation; no sibling environmental effects were detected.

Conclusions:

• Anthropometric traits exhibit substantial heritability driven by both major genes and polygenes.
• Polygenic inheritance is a primary driver of anthropometric variation, especially for shape factors.
• The genetic architecture of anthropometric traits differs between ethnic groups, with distinct contributions from major genes and polygenes.