Cheng Rong, Park Naeun, Hodge Susan E, Juo Suh-Hang Hank
Columbia Genome Center, Columbia University, 1150 St, Nicholas Avenue, New York, New York, USA.
BMC Genet. 2003 Dec 31;4 Suppl 1(Suppl 1):S20. doi: 10.1186/1471-2156-4-S1-S20.
Family studies are often conducted in a cross-sectional manner without long-term follow-up data. The relative contribution of a gene to a specific trait could change over the lifetime. The Framingham Heart Study offers a unique opportunity to investigate potential gene x time interaction. We performed linkage analysis on the body mass index (BMI) measured in 1970, 1978, and 1986 for this project.
We analyzed the data in two different ways: three genome-wide linkage analyses on each exam, and one genome-wide linkage analysis on the mean of the three measurements. Variance-component linkage analyses were performed by the SOLAR program. Genome-wide scans show consistent evidence of linkage of quantitative trait loci (QTLs) on chromosomes 3, 6, 9, and 16 in three measurements with a maximum multipoint LOD score > 2.2. However, only chromosome 9 has a LOD score = 2.14 when the mean values were analyzed. More interestingly, we found potential gene x environment interactions: increasing LOD scores with age on chromosomes 3, 9, and 16 and decreasing LOD scores on chromosome 6 in the three exams.
The results indicate two points: 1) it is possible that a gene (or genes) influencing BMI is (are) up- or down-regulated as people aged due to aging process or changes in lifestyle, environments, or genetic epistasis; 2) using mean values from longitudinal data may reduce the power to detect linkage and may have no power to detect gene x time, and/or gene x gene interactions.
家族研究通常以横断面方式进行,缺乏长期随访数据。基因对特定性状的相对贡献可能会在一生中发生变化。弗雷明汉心脏研究提供了一个独特的机会来研究潜在的基因×时间相互作用。我们针对该项目对1970年、1978年和1986年测量的体重指数(BMI)进行了连锁分析。
我们以两种不同方式分析数据:对每次检查进行三次全基因组连锁分析,以及对三次测量的均值进行一次全基因组连锁分析。通过SOLAR程序进行方差成分连锁分析。全基因组扫描显示,在三次测量中,3号、6号、9号和16号染色体上的数量性状位点(QTL)存在一致的连锁证据,最大多点对数优势(LOD)得分>2.2。然而,在分析均值时,只有9号染色体的LOD得分为2.14。更有趣的是,我们发现了潜在的基因×环境相互作用:在三次检查中,3号、9号和16号染色体上的LOD得分随年龄增加,而6号染色体上的LOD得分下降。
结果表明两点:1)由于衰老过程、生活方式、环境或基因上位性的变化,影响BMI的一个或多个基因可能会随着年龄增长而上调或下调;2)使用纵向数据的均值可能会降低检测连锁的能力,并且可能无法检测到基因×时间和/或基因×基因相互作用。