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Somatic evolution of cells within the body is well known to lead to cancers. However, spread of somatic mutations within a tissue over time may also contribute to the pathogenesis of non-neoplastic diseases. Recent years have seen the publication of many studies aiming to characterize somatic evolution in healthy tissues. A logical next step is to extend such work to diseased conditions. As our understanding of the interplay between somatic mutations and non-neoplastic disease grows, opportunities for the joint study of germline and somatic variants will present themselves. Here, we present our thoughts on the utility of somatic mutations for understanding both the causes and consequences of common complex disease and the challenges that remain for the joint study of the soma and germline.

The polygenic risk score for schizophrenia (SZ-PRS) is associated with creativity and psychiatric disorders, including cannabis use. We have investigated the selection pressures on sequence variants that predispose to schizophrenia in the Icelandic population and find no evidence of selective advantage of a high SZ-PRS. Rare copy-number variants conferring moderate to high risk of psychiatric illness are, however, associated with having fewer children and are under negative selection. We also examined the correlation between SZ-PRS and the number of relationships producing offspring in 81,713 adult Icelanders without diagnosis of schizophrenia. SZ-PRS is associated with increased likelihood of having offspring with more than one mate (P = 7.9 x 10-12). Thus, while common variants that increase schizophrenia risk may not be under strong selection they influence mating behaviour in adults who do not have the disorder.