A Genome-wide Association Study of Autism Reveals a Common Novel Risk Locus at 5p14.1


*Corresponding authors: Margaret A. Pericak-Vance, Ph.D., Dr. John T. Macdonald Foundation Professor of Human Genomics, Director, Miami Institute for Human Genomics, 1120 NW 14th Street, CRB-819 (M860), Miami, Florida 33136. Tel: (305) 243-2308; Fax: (305) 243-2396; E-mail: mpericak@med.miami.edu Jonathan L. Haines, Ph.D., T.H. Morgan Professor of Human Genetics, Professor, Molecular Physiology & Biophysics, Director, Center for Human Genetics Research, 519 Light Hall, Vanderbilt University Medical Center, Nashville, TN 37232-0700. Tel: (615) 343-5851; Fax: (615) 343-8619; E-mail: jonathan@chgr.mc.vanderbilt.edu


Although autism is one of the most heritable neuropsychiatric disorders, its underlying genetic architecture has largely eluded description. To comprehensively examine the hypothesis that common variation is important in autism, we performed a genome-wide association study (GWAS) using a discovery dataset of 438 autistic Caucasian families and the Illumina Human 1M beadchip. 96 single nucleotide polymorphisms (SNPs) demonstrated strong association with autism risk (p-value < 0.0001). The validation of the top 96 SNPs was performed using an independent dataset of 487 Caucasian autism families genotyped on the 550K Illumina BeadChip. A novel region on chromosome 5p14.1 showed significance in both the discovery and validation datasets. Joint analysis of all SNPs in this region identified 8 SNPs having improved p-values (3.24E-04 to 3.40E-06) than in either dataset alone. Our findings demonstrate that in addition to multiple rare variations, part of the complex genetic architecture of autism involves common variation.