| 1 | Genome Res. 2004 Jul 14: 1345-9 |
|---|---|
| PMID | 15231749 |
| Title | Genetic structure adds power to detect schizophrenia susceptibility at SLIT3 in the Chinese Han population. |
| Abstract | The Chinese Han population, the largest population in the world, has traditionally been geographically divided into two parts, the Southern Han and Northern Han. In practice, however, these commonly used ethnic labels are both insufficient and inaccurate as descriptors of inferred genetic clustering, and can lead to the observation of "spurious association" as well as the concealment of real association. In this study, we attempted to address this problem by using 14 microsatellite markers to reconstruct the population genetic structure in 768 Han Chinese samples, including 384 Southern Han and 384 Northern Han, and in samples from Chinese minorities including 48 Yao and 48 BouYei subjects. Furthermore, with a dense set of markers around the region 5q34-35, we built fine-scale haplotype networks for each population/subpopulation and tested for association to schizophrenia susceptibility. We found that more variants in SLIT3 tend to associate with schizophrenia susceptibility in the genetically structured samples, compared to geographically structured samples and samples without identified population substructure. Our results imply that identifying the hidden genetic substructure adds power when detecting association, and suggest that SLIT3 or a nearby gene is associated with schizophrenia. |
| SCZ Keywords | schizophrenia |
| 2 | Mol Autism 2014 -1 5: 1 |
| PMID | 24410847 |
| Title | Exome sequencing of extended families with autism reveals genes shared across neurodevelopmental and neuropsychiatric disorders. |
| Abstract | Autism spectrum disorders (ASDs) comprise a range of neurodevelopmental conditions of varying severity, characterized by marked qualitative difficulties in social relatedness, communication, and behavior. Despite overwhelming evidence of high heritability, results from genetic studies to date show that ASD etiology is extremely heterogeneous and only a fraction of autism genes have been discovered. To help unravel this genetic complexity, we performed whole exome sequencing on 100 ASD individuals from 40 families with multiple distantly related affected individuals. All families contained a minimum of one pair of ASD cousins. Each individual was captured with the Agilent SureSelect Human All Exon kit, sequenced on the Illumina Hiseq 2000, and the resulting data processed and annotated with Burrows-Wheeler Aligner (BWA), Genome Analysis Toolkit (GATK), and SeattleSeq. Genotyping information on each family was utilized in order to determine genomic regions that were identical by descent (IBD). Variants identified by exome sequencing which occurred in IBD regions and present in all affected individuals within each family were then evaluated to determine which may potentially be disease related. Nucleotide alterations that were novel and rare (minor allele frequency, MAF, less than 0.05) and predicted to be detrimental, either by altering amino acids or splicing patterns, were prioritized. We identified numerous potentially damaging, ASD associated risk variants in genes previously unrelated to autism. A subset of these genes has been implicated in other neurobehavioral disorders including depression (SLIT3), epilepsy (CLCN2, PRICKLE1), intellectual disability (AP4M1), schizophrenia (WDR60), and Tourette syndrome (OFCC1). Additional alterations were found in previously reported autism candidate genes, including three genes with alterations in multiple families (CEP290, CSMD1, FAT1, and STXBP5). Compiling a list of ASD candidate genes from the literature, we determined that variants occurred in ASD candidate genes 1.65 times more frequently than in random genes captured by exome sequencing (P?=?8.55 × 10-5). By studying these unique pedigrees, we have identified novel DNA variations related to ASD, demonstrated that exome sequencing in extended families is a powerful tool for ASD candidate gene discovery, and provided further evidence of an underlying genetic component to a wide range of neurodevelopmental and neuropsychiatric diseases. |
| SCZ Keywords | schizophrenia |