Researchers sequenced the exomes of 21,958 people with serious mental illness or severe major depressive disorder and 19,826 controls from the Mision Origen biobank in the Paisa genetic isolate of Colombia, testing predicted deleterious variants transdiagnostically. Seven genes were associated, five of them newly implicated, with the association at four driven by variants common in the Paisa through a founder effect. The strongest signal, a frameshift variant in ADAP1 at an allele frequency of about 0.4%, raised risk of both schizophrenia and bipolar disorder more than threefold, and carriers differed from other cases on psychotic, manic and cognitive phenotypes extracted from electronic health records.
Why it is interesting: A founder population with linked records yields a variant of intermediate frequency and large effect, between what common-variant and ultra-rare-variant studies reach.