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Inflammatory and infectious upper respiratory diseases (ICD-10: J30-J39), such as diseases of the sinonasal tract, pharynx and larynx, are growing health problems yet their genomic similarity is not known. We analyze genome-wide association to eight upper respiratory diseases (61,195 cases) among 260,405 FinnGen participants, meta-analyzing diseases in four groups based on an underlying genetic correlation structure. Aiming to understand which genetic loci contribute to susceptibility to upper respiratory diseases in general and its subtypes, we detect 41 independent genome-wide significant loci, distinguishing impact on sinonasal or pharyngeal diseases, or both. Fine-mapping implicated non-synonymous variants in nine genes, including three linked to immune-related diseases. Phenome-wide analysis implicated asthma and atopic dermatitis at sinonasal disease loci, and inflammatory bowel diseases and other immune-mediated disorders at pharyngeal disease loci. Upper respiratory diseases also genetically correlated with autoimmune diseases such as rheumatoid arthritis, autoimmune hypothyroidism, and psoriasis. Finally, we associated separate gene pathways in sinonasal and pharyngeal diseases that both contribute to type 2 immunological reaction. We show shared heritability among upper respiratory diseases that extends to several immune-mediated diseases with diverse mechanisms, such as type 2 high inflammation. The shared genetics between upper respiratory diseases have not been well studied. Here, the authors find shared and distinct genetic loci for pharyngeal and sinonasal inflammatory conditions, which show shared heritability with autoimmune conditions and immune deficiency, highlighting the TNFR2 pathway.

Background Hereditary factors, including single genetic variants and family history, can be used for targeting colorectal cancer (CRC) screening, but limited data exist on the impact of polygenic risk scores (PRS) on risk-based CRC screening. Methods Using longitudinal health and genomics data on 453,733 Finnish individuals including 8801 CRC cases, we estimated the impact of a genome-wide CRC PRS on CRC screening initiation age through population-calibrated incidence estimation over the life course in men and women. Results Compared to the cumulative incidence of CRC at age 60 in Finland (the current age for starting screening in Finland), a comparable cumulative incidence was reached 5 and 11 years earlier in persons with high PRS (80–99% and >99%, respectively), while those with a low PRS (< 20%) reached comparable incidence 7 years later. The PRS was associated with increased risk of post-colonoscopy CRC after negative colonoscopy (hazard ratio 1.76 per PRS SD, 95% CI 1.54–2.01). Moreover, the PRS predicted colorectal adenoma incidence and improved incident CRC risk prediction over non-genetic risk factors. Conclusions Our findings demonstrate that a CRC PRS can be used for risk stratification of CRC, with further research needed to optimally integrate the PRS into risk-based screening.

Differences in disease risk are linked to inherited genetic variation and social circumstances, but how these factors jointly relate to multiple diseases is not fully understood. This study investigates the independent and combined associations of genetic predisposition and socioeconomic status with common diseases. We analyzed data from 743,194 adults from three biobank studies in Finland and the United Kingdom, including European and non-European ancestry individuals. Genetic predisposition was measured using polygenic scores for 19 common diseases. Socioeconomic status was assessed through education and occupation. We evaluated associations of genetic and socioeconomic factors with disease risk and whether genetic associations differed across education levels. Models including both genetic and educational factors were compared with models including only one factor and models including their interaction. Here, we show that both genetic predisposition and socioeconomic status are associated with disease risk across most conditions. For seven diseases, genetic associations are stronger in highly educated groups, while occupation shows smaller differences. Patterns are generally consistent across ancestry groups, though education associations are less stable in non-European individuals. While both education and polygenic scores independently improved prediction, combining both provided additional modest improvement to prediction for 16 and 12 out of 19 diseases in FinnGen and the UK Biobank, respectively. Genetic variation and social circumstances are linked to differences in disease risk both independently, and in combination with one another. Considering both factors modestly improves identification of higher-risk groups and highlights the value of accounting for social context alongside inherited variation in population-level assessments.