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This article is part of the supplement: Genetic Analysis Workshop 13: Analysis of Longitudinal Family Data for Complex Diseases and Related Risk Factors

Open Access Proceedings

Comparison of the linkage results of two phenotypic constructs from longitudinal data in the Framingham Heart Study: analyses on data measured at three time points and on the average of three measurements

Rong Cheng1, Naeun Park1, Susan E Hodge2 and Suh-Hang Hank Juo13*

Author Affiliations

1 Columbia Genome Center, Columbia University, 1150 St. Nicholas Avenue, New York, New York, USA

2 New York State Psychiatric Institute, Columbia University, 1051 Riverside Drive, New York, New York, USA

3 Department of Epidemiology, Columbia University, New York, New York, USA

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BMC Genetics 2003, 4(Suppl 1):S20  doi:10.1186/1471-2156-4-S1-S20

Published: 31 December 2003



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 × 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 × 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 × time, and/or gene × gene interactions.