Loci nominally associated with autism from genome-wide analysis show enrichment of brain expression quantitative trait loci but not lymphoblastoid cell line expression quantitative trait lociReportar como inadecuado




Loci nominally associated with autism from genome-wide analysis show enrichment of brain expression quantitative trait loci but not lymphoblastoid cell line expression quantitative trait loci - Descarga este documento en PDF. Documentación en PDF para descargar gratis. Disponible también para leer online.

Molecular Autism

, 3:3

First Online: 16 May 2012Received: 27 January 2012Accepted: 22 March 2012

Abstract

BackgroundAutism spectrum disorder is a severe early onset neurodevelopmental disorder with high heritability but significant heterogeneity. Traditional genome-wide approaches to test for an association of common variants with autism susceptibility risk have met with limited success. However, novel methods to identify moderate risk alleles in attainable sample sizes are now gaining momentum.

MethodsIn this study, we utilized publically available genome-wide association study data from the Autism Genome Project and annotated the results P <0.001 for expression quantitative trait loci present in the parietal lobe GSE35977, cerebellum GSE35974 and lymphoblastoid cell lines GSE7761. We then performed a test of enrichment by comparing these results to simulated data conditioned on minor allele frequency to generate an empirical P-value indicating statistically significant enrichment of expression quantitative trait loci in top results from the autism genome-wide association study.

ResultsOur findings show a global enrichment of brain expression quantitative trait loci, but not lymphoblastoid cell line expression quantitative trait loci, among top single nucleotide polymorphisms from an autism genome-wide association study. Additionally, the data implicates individual genes SLC25A12, PANX1 and PANX2 as well as pathways previously implicated in autism.

ConclusionsThese findings provide supportive rationale for the use of annotation-based approaches to genome-wide association studies.

KeywordsAutism annotation cerebellum enrichment expression quantitative trait eQTL GWAS LCL pannexin parietal SLC25A12 AbbreviationsASDautism spectrum disorder

AGPAutism Genome Project

eQTLexpression quantitative trait loci

GWASgenome-wide association study

LCLlymphoblastoid cell line

PANX1pannexin 1

PANX2pannexin 2

SNPsingle nucleotide polymorphism

SLC25A12solute carrier family 25 member 12.

Electronic supplementary materialThe online version of this article doi:10.1186-2040-2392-3-3 contains supplementary material, which is available to authorized users.

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Autor: Lea K Davis - Eric R Gamazon - Emily Kistner-Griffin - Judith A Badner - Chunyu Liu - Edwin H Cook - James S Sutcliffe

Fuente: https://link.springer.com/







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