The two SNPs with the strongest associations to schizophrenia

According to a GWAS published yesterday (using a sample of individuals with European ancestry only), they are in these genes:

1) HLA-DQA1: this codes for a receptor involved in antigen presenting cells, and might be related to autoimmune disorders. This speculative paper bites the bullet on the connection and suggests that better treatment for pathogens could reduce the prevalence of the disorder. The hypothesis seems testable via epidemiological data–does more pathogen treatment (or treatment of a specific type) lead to a decreased incidence of schizophrenia? I doubt there’s a big effect here; otherwise, we’d probably already know.

2) MADL1L: this codes for a protein which helps regulate cell division (mitosis), almost all of which occurs in the brain during development. Although schizophrenia is often considered a developmental disorder, it doesn’t typically present until young adulthood, with some studies reporting a mean age of onset of 30. This suggests that the spatial pattern and distribution of cells set down early in development can probabilistically impact outcomes much later in life. (This is as opposed to a gene being involved in synapse remodeling, which is common throughout adulthood.)

Multiple SNPs within both of these genes have significant p-values, which makes the explanation of linkage disequilibrium seem less likely. (Plus, the authors checked the haplotype maps for this.)

Reference

Jia P, Wang L, Fanous AH, Pato CN, Edwards TL, et al. (2012) Network-Assisted Investigation of Combined Causal Signals from Genome-Wide Association Studies in Schizophrenia. PLoS Comput Biol 8(7): e1002587. doi:10.1371/journal.pcbi.1002587