Effects of Updating Linkage Evidence Across Subsets of Data: Reanalysis of the Autism Genetic Resource Exchange Data Set

Overview

Journal Am J Hum Genet

Publisher Cell Press

Specialty Genetics

Date 2005 Feb 25

PMID 15729670

Citations 13

Authors

Christopher W Bartlett

Rhinda Goedken

Veronica J Vieland

Affiliations

Soon will be listed here.

Abstract

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.

Citing Articles

The Importance of Large-Scale Genomic Studies to Unravel Genetic Risk Factors for Autism.

Nobrega I, Teles E Silva A, Yokota-Moreno B, Sertie A Int J Mol Sci. 2024; 25(11).

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Narrowing down the region responsible for 1q23.3q24.1 microdeletion by identifying the smallest deletion.

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An autism case history to review the systematic analysis of large-scale data to refine the diagnosis and treatment of neuropsychiatric disorders.

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Replication of linkage at chromosome 20p13 and identification of suggestive sex-differential risk loci for autism spectrum disorder.

Werling D, Lowe J, Luo R, Cantor R, Geschwind D Mol Autism. 2014; 5(1):13.

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