Genome-Wide Variants Significantly Contribute to Longitudinal Phenotype Dynamics

Music City Center 

Considerable progress has been made in quantifying the heritability of cross-sectional traits, but analyzing longitudinal phenotypic trajectories remains challenging. This study introduces a mixed model integrating genome-wide genetic variants to disentangle heritability metrics on baseline trait levels and rates of change over time, providing insights into both static and dynamic aspects of traits. Key challenges primarily stem from the potential for large-scale studies, truncated estimates due to limited measurements per subject, joint genetic effects. To address these complexities, we compare the average information restricted maximum likelihood algorithm, augmented with meta analysis to tackle truncation, with the restricted Haseman-Elston regression approach, which avoids reliance on precision matrix computations. Using these approaches, we analyzed 6,948,674 genome-wide common variants to study PSA trajectories in males from the PLCO Screening Trial. Our findings reveal moderate heritability of baseline PSA levels but significant heritability of PSA velocity, underscoring an increasing heritability trend with age and enabling more accurate prediction of disease risk.

AI-REML algorithm

truncation

REHE method

heritability

PSA level

large-scale studies 

Biometrics Section