Beck Stephanie R, Brown W Mark, Williams Adrienne H, Pierce June, Rich Stephen S, Langefeld Carl D
Department of Public Health Sciences, Wake Forest University School of Medicine, Winston-Salem, North Carolina, USA.
BMC Genet. 2003 Dec 31;4 Suppl 1(Suppl 1):S31. doi: 10.1186/1471-2156-4-S1-S31.
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.
随着纵向数据的可得性，特定年龄（分层）或年龄调整的基因分析有潜力定位不同的假定性状影响位点。如果年龄在所研究的范围内不影响位点特异性外显率函数，年龄分层分析对于单个性状往往会产生可比的结果。然而，当位点特异性外显率函数依赖于年龄时，年龄分层的结果在不同年龄层之间应该会有所不同。在本文中，对弗雷明汉心脏研究的一个子集进行了年龄分层和年龄调整的数量性状基因座（QTL）连锁分析，以研究身高、体重、体重指数（BMI）和收缩压。分层包括三个年龄组中每组都有数据的个体：31 - 49岁、50 - 60岁、61 - 79岁。使用SOLAR进行全基因组QTL分析。在所有年龄组中，在14q11.2染色体上靠近标记GATA74E02A处检测到身高的连锁信号（31 - 49岁组的LOD = 2.38，50 - 60岁组的LOD = 1.84，61 - 79岁组的LOD = 2.45）。在31 - 49岁年龄组中，在3q22染色体上发现了与BMI连锁的证据（GATA3C02，LOD = 2.89，p = 0.0003），与体重的信号位于同一位置（LOD = 3.10，p = 0.0002）。在31 - 49岁年龄组中，1p22.1染色体上的BMI（LOD = 2.21，p = 0.0014）和体重（LOD = 2.47，p = 0.0007）也得到了连锁支持。我们的年龄分层结果表明，使用基因组扫描和方差成分方法有助于检测早期和/或晚期基因表达，可能识别出长时间表达并影响多个相关性状的QTL。
