Age-stratified QTL genome scan analyses for anthropometric measures

With the availability of longitudinal data, age-specific ( stratified) or age-adjusted genetic analyses have the potential to localize different putative trait influencing loci. If age does not influence the locus-specific penetrance function within the range examined, age-stratified analyses will tend to yield comparable results for an individual trait. However, age-stratified results should vary across age strata when the locus-specific penetrance function is age dependent. In this paper, age-stratified and age-adjusted quantitative trait loci (QTL) linkage analyses were contrasted for height, weight, body mass index (BMI), and systolic blood pressure on a subset of the Framingham Heart Study. The strata comprised individuals with data present in each of three age groups: 31 - 49, 50 - 60, 61 79. Genome-wide QTL analyses were performed using SOLAR. Over all ages, a linkage signal for height was detected on chromosome 14q11.2 near marker GATA74E02A ( LOD for ages 31 - 49 = 2.38, LOD for ages 50 - 60 = 1.84, LOD for ages 61 - 79 = 2.45). Evidence of linkage to BMI in the 31 - 49 age group was found on chromosome 3q22 ( GATA3C02, LOD = 2.89, p = 0.0003) at the same location as the signal for weight ( LOD = 3.10, p = 0.0002). Linkage was also supported on chromosome 1p22.1 for BMI ( LOD = 2.21, p = 0.0014) and weight ( LOD = 2.47, p = 0.0007) in the 31 - 49 age group. Our age-stratified results suggest that QTL that are expressed over long periods of time and affecting multiple, correlated traits may be identified using genome scan and variance-component methodology to help detect early and/or late gene expression.