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Summary: Aiming to identify pleiotropic genomic loci for bone mineral density and bone size, we performed a bivariate GWAS in five discovery samples and replicated in two large-scale samples. We identified 2 novel loci at 2q37.1 and 6q26. Our findings provide insight into common genetic architecture underlying both traits. Introduction: Bone mineral density (BMD) and bone size (BS) are two important factors that contribute to the development of osteoporosis and osteoporotic fracture. Both BMD and BS are highly heritable and they are genetically correlated. In this study, we aim to identify pleiotropic loci associated with BMD and BS. Methods: We conducted a bivariate genome-wide association (GWA) analysis of hip BMD and hip BS in 6180 participants from 5 samples, followed by in silico replication in the UK Biobank study of BMD (N = 426,824) and the deCODE study of BS (N = 28,954), respectively. Results: SNPs from 2 genomic loci were significant at the genome-wide significance (GWS) level (p lt; 5 × 10−8) in the discovery samples and were successfully replicated in the replication samples (2q37.1, lead SNP rs7575512, discovery p = 1.49 × 10−10, replication p = 0.05; 6q26, lead SNP rs1040724, discovery p = 1.95 × 10−8, replication p = 0.03). Functional annotations suggested functional relevance of the identified variants to bone development. Conclusion: Our findings provide insight into the common genetic architecture underlying BMD and BS, and enhance our understanding of the potential mechanism of osteoporosis fracture. [ABSTRACT FROM AUTHOR]

We assessed the association between long-term joint exposure to ambient air pollutants and the risk of laryngeal cancer and whether this risk was modified by genetic susceptibility. We used a multivariable Cox proportional hazards regression model to analyze data from UK Biobank to determine the relationship between long-term exposure to air pollutants-nitric oxide (NO), nitrogen dioxide (NO 2 ), and 2.5-µm and 10-µm particulate matter (PM 2.5 and PM 10 ) and the risk of laryngeal cancer. In multivariable-adjusted models, in model 3 and compared with the participants with lower quintile scores for air pollution, the participants with the highest quintile scores for air pollution had a higher laryngeal cancer risk. The observed association was more pronounced among the participants who were female, were smokers, had a systolic blood pressure equal to or greater than 120 mmHg, and had diabetes. Compared with the participants with a low GRS and the lowest quintile score for air pollution exposure, those with an intermediate GRS and the highest quintile score for air pollution exposure had a higher risk of laryngeal cancer. Long-term exposure to NO 2 , NO, or PM 2.5 , individually or jointly, was associated with a risk of incident laryngeal cancer, especially in the participants with an intermediate GRS., (© 2023. The Author(s).)