Studies that have sequenced the exomes of patients with schizophrenia and autism provide a bottom up answer to the same question: rather than assessing the impact of common variants, they search for rare coding variation. Two studies of schizophrenia, one of 14 trios (two unaffected parents and one affected child) [2•], the other of 53 sporadic cases, 22 controls and their parents, both reported de novo mutations in patients [3•]. The smaller study reported 4 non-sense mutations (out of a total of 15), significantly higher than the expected rate, while the larger study identified a ratio of 32 non-synonymous mis-sense mutations to 2 synonymous mutations, again significantly elevated over expectations.
