Close genetic relationships between a spousal pair with autism-affected children and high minor allele content in cases in autism-associated SNPs.

Parents of children affected with autism spectrum disorders (ASD) often have mild forms of autistic-like characteristics. Past studies have focused on searching for individual genetic risk loci of ASD. Here we studied the overall properties of the genomes of ASD trios by using previously published genome-wide data for common SNPs. The pairwise genetic distance (PGD) between a spousal pair with ASD-affected children was found smaller than that of a random pair selected among the spouses in the ASD trios, and spousal relatedness correlated with severe forms of ASD. Furthermore, for a set of 970 ASD associated SNPs, cases showed higher homozygous minor allele content than parents. These results indicate new genetic elements in the broad phenotypes of parents with ASD-affected offspring and in ASD pathogenesis.

Enrichment of Minor Alleles of Common SNPs and Improved Risk Prediction for Parkinson's Disease.

Parkinson disease (PD) is the second most common neurodegenerative disorder in the aged population and thought to involve many genetic loci. While a number of individual single nucleotide polymorphisms (SNPs) have been linked with PD, many remain to be found and no known markers or combinations of them have a useful predictive value for sporadic PD cases. The collective effects of genome wide minor alleles of common SNPs, or the minor allele content (MAC) in an individual, have recently been shown to be linked with quantitative variations of numerous complex traits in model organisms with higher MAC more likely linked with lower fitness. Here we found that PD cases had higher MAC than matched controls. A set of 37564 SNPs with MA (MAF < 0.4) more common in cases (P < 0.05) was found to have the best predictive accuracy. A weighted risk score calculated by using this set can predict 2% of PD cases (100% specificity), which is comparable to using familial PD genes to identify familial PD cases. These results suggest a novel genetic component in PD and provide a useful genetic method to identify a small fraction of PD cases.