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Answer to troublesome question of why some genetic assoc. studies have failed replication attempts
Date:4/3/2008

childhood and diminishes after age 45.

"This is important because it demonstrates that genetic effects can vary over time," said Jessica Lasky-Su, Instructor at Harvard Medical School and Brigham and Women's Hospital. "In this example, the marker may increase obesity in early life and then as time goes on, other effects become stronger, and the influence of this marker diminishes. It is likely that many other genetic variants also act in this fashion." Lasky-Su is co-lead author of the study with Helen Lyon of Children's Hospital Boston.

To test rs1455832 further, the researchers examined its association with obesity and with age in eight other study populations comprising 13,584 individuals. Five international centers participated, including studies from Costa Rica, Greece, Poland, Iceland, and Germany. The interaction was observed in five of the eight replicate samples with statistically significant results. The authors note that this interaction would have been missed in all but one of the replication samples if they had failed to incorporate the age-dependent effect in the association analysis.

Said Lange, "We are now in an era where scanning entire genomes for associations with diseases is rapid. In assessing the resulting data, it will be important for scientists to keep in mind the significance of age, otherwise findings may not be replicated or may be overlooked entirely."

The importance of age-dependent genetic effects for BMI was suggested in a 2003 paper published by researchers at the University of Texas MD Anderson Cancer Center in the European Journal of Human Genetics that described a genome-wide scan for genes related to BMI. However, the incorporation of age-dependent genetic effects for BMI into genetic analyses remains uncommon.


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Contact: Christina Roache
croache@hsph.harvard.edu
617-432-6052
Harvard School of Public Health
Source:Eurekalert

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