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

Boston, MA - A team of researchers from Harvard School of Public Health (HSPH), Brigham and Women's Hospital (BWH), and elsewhere have described a possible reason why some studies have been unable to replicate associations between genes and traits -- namely that the strength of a gene/trait association might vary with age and that current study designs typically fail to take that into account. The paper was selected for early publication online on the American Journal of Human Genetics (AJHG) web site on April 3, 2008, and will appear in the April 11 print issue of the journal.

Said Christoph Lange, HSPH Associate Professor of Biostatistics and senior author: "In reexamining a vast amount of original data from an earlier study, we have illustrated clearly that genetic effects for complex traits can vary by age and that such an interaction can prevent independent replications of the work if this variable is not taken into account in planning and analyzing the study. This insight has implications for all fellow researchers in genetic association studies."

In 2006, Lange was a co-author of a paper in Science that found a common genetic variant, or SNP, that is associated with adult and childhood obesity. The association was confirmed in some, but not all, cohorts.

When more data became available, Lange and collaborators reanalyzed the original data, plus genetic information from 399 additional individuals. Subjects participated in the Framingham Heart Study offspring cohort. More than 116,200 SNPs were initially genotyped, of which 86,604 were used in the association analyses. Measurements of body mass index (BMI) were taken six times over an average of 23 1/2 years. BMI is weight in kilograms divided by the square of height in meters.

The researchers found a second common genetic variant called rs1455832 in the ROBO1 gene that affects obesity. More to the point, the variant's influence on obesity appears to be strongest during
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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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