Background It has long been established that schizophrenia is highly heritable and family history is a reliable predictor for the disorder. However, both GWAS and exome sequencing studies fail to answer the question what genetic variants constitute family history. While it is generally believed that cases from families with multiple affected individuals have higher genetic risk loading, it is not clear to what extent and where do these cases differ from sporadic cases where there is no apparent family history of mental disorders. Whole genome sequencing of cases from families with multiple affected individuals may help to answer this question. Methods We selected 20 Chinese families with at least 2 affected siblings and 1 unaffected sibling and conducted whole genome sequencing. Of these families, 7 had both parents. Some of the parents had schizophrenia or other psychiatric disorders. We used the GATK protocols to align sequence reads, call and annotate variants. In the first pass of analyses, we generated a list of variants for each family that were found in affected individuals only. We matched the list across the families and generated a new list of variants that were shared for at least 2 families. Variants in this second list were functionally annotated, and analyzed for enrichment for biological pathways. Results We found that there were 6 SNVs that were found in the affected individuals in 6 families. Three of them were in the ADAD2 gene, a nuclear double stranded RNA binding protein. One of the 3 SNVs in ADAD2 was non-synonymous, rs11149631, changing Gly to Arg. The other 3 were in NUP205, HNF4G and MAGEC1 genes. In the analyses of functional variants, we found that non-synonymous SNVs found in at least two families (640 SNVs in 539 genes) were enriched in EMC-receptor interaction pathway and cell-matrix adhesion process. When we tested whether these genes were enriched in any known diseases, we identified childhood onset schizophrenia. Of the 16 genes involved in childhood onset schizophrenia, 5 genes (SEZ6, PDZRN3, HSPG2, ARL16 and ITGA6) were in our list. Discussion Our overrepresentation enrichment analyses for non-synonymous SNVs found in affected individuals in two or more families indicate that the EMC-receptor interaction and cell-matrix adhesion are involved in schizophrenia, consistent with previous report from other GWAS and sequencing analyses. The same genes are also enriched for genes involved in childhood onset schizophrenia, implying that there may be a link or similarity between childhood onset schizophrenia and cases from families with multiple affected individuals. To our knowledge, this is the first report of such connection. Furthermore, our analyses also suggest that ADAD2 is a top candidate and further validation is justified.