Improving access to psychiatric outpatient care through feedback-informed treatment: a study on waiting times and therapy duration in Sweden.

Proteins circulating in blood are under genetic control, and linking protein quantitative trait loci (pQTLs) to complex diseases can inform drug target selection or drug repurposing in humans. The most comprehensive studies so far used affinity-based methods, using either antibodies or single-stranded DNA aptamers, to measure up to ~5,000 predefined proteins. However, between one-third and half of the assayed proteins could not be linked to variation near or within the corresponding protein-coding gene even in the studies of >30,000 participants. Mass spectrometry (MS)-based proteomic studies included 500 to 1,200 proteins at moderate sample size, identifying proteins and pQTLs not detected in larger affinity-based efforts. However, the large dynamic range of the plasma proteome limited the coverage of low-abundant signaling proteins. Nanoparticle (NP)-based enrichment coupled with next-generation MS instruments can now identify >5,000 proteins circulating in blood at population scale, providing unique opportunities for translational research. Here we present a comprehensive MS-based plasma proteogenomic study of >5,700 protein groups robustly measured in >1,400 volunteers from the Genes & Health (G&H) cohort of adult British Bangladeshi and British Pakistani ancestry participants. These communities are at disproportionally high risk for cardiometabolic and other diseases, and have been historically underrepresented in genetic studies. High rates of autozygosity in this cohort further enable the detection of rare variants as homozygotes, providing additional power for nonadditive genetic discovery. We performed a comprehensive MS-based plasma proteomic study using the Seer Proteograph XT (referred to ‘Seer XT’ hereafter), identifying a total of 8,079 protein groups () detected at least once across 1,612 plasma samples of recalled volunteers of the G&H cohort of British Bangladeshi and Pakistani ancestry participants ( = 1,464, mean age = 43.4 years (12.2 s.d.), 55.9% females; mean body mass index = 27.7 kg m (5.2 s.d.); 19.4% current smokers; Supplementary Table ). This included 5,768 protein groups seen in ≥70% of samples, demonstrating the depth and coverage of the MS-based plasma proteome.