Linkage Analysis Of Myostatin Pathway Genes On Individual Factor Scores Of Human Muscularity

Abstract

PURPOSE To determine the underlying constructs of muscular strength and anthropometric measurements by principal components analyses and to test whether individual factor scores are linked to variation in the myostatin pathway genes. METHODS An orthogonal principal components analysis was carried out on a large set of muscle strength and body measurements from 748 male Caucasian siblings. Furthermore, it was rationalized that, reducing the number of variables that capture the spectrum of a complex trait, should enhance power to detect linkage. From a biological point of view, this facilitates the interpretation of linkage results as the underlying structure is considered rather than one specific measurement. In a sample of 367 siblings, non-parametric multipoint linkage analysis was performed on the individual factor scores with genetic markers for nine key proteins from the myostatin pathway. RESULTS A clear factor structure emerged: flexion, extension and muscle endurance factors were found for trunk strength; flexion, extension, muscle endurance and fast muscle contraction were the factors for knee and elbow strength. The photoscopic somatotype components of Sheldon emerged from principal components analysis of body measurements: fatness, muscularity and length. Highest LOD score was 1.67 (P = 0.003) on chromosome 2 for knee extension, and the fat and muscle factors showed LOD scores of 1.24 (P = 0.008) and 1.35 (P = 0.006) respectively with markers on chromosome 13. All other factors had LOD scores < 1 for all markers. CONCLUSIONS Since earlier analyses on the raw data did reveal significant linkage (LOD > 2.5), we conclude that the use of factor scores for linkage analysis had lower power in the present study.