Journal
AMERICAN JOURNAL OF HUMAN GENETICS
Volume 76, Issue 4, Pages 688-695Publisher
CELL PRESS
DOI: 10.1086/429345
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Funding
- NHLBI NIH HHS [T32 HL07638, T32 HL007638] Funding Source: Medline
- NIMH NIH HHS [R01 MH052841] Funding Source: Medline
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Results of autism linkage studies have been difficult to interpret across research groups, prompting the use of ever-increasing sample sizes to increase power. However, increasing sample size by pooling disparate collections for a single analysis may, in fact, not increase power in the face of genetic heterogeneity. Here, we applied the posterior probability of linkage (PPL), a method designed specifically to analyze multiple heterogeneous data sets, to the Autism Genetic Resource Exchange collection of families by analyzing six clinically defined subsets of the data and updating the PPL sequentially over the subsets. Our results indicate a substantial probability of linkage to chromosome 1, which had been previously overlooked; our findings also provide a further characterization of the possible parent-of-origin effects at the 17q11 locus that were previously described in this sample. This analysis illustrates that the way in which heterogeneity is addressed in linkage analysis can dramatically affect the overall conclusions of a linkage study.
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