Identifying BMI-associated genes via a genome-wide multi-omics integrative approach using summary data.

OBJECTIVE: This study aims to identify BMI-associated genes by integrating aggregated summary information from different omics data. METHODS: We conducted a meta-analysis to leverage information from a genome-wide association study (n = 339 224), a transcriptome-wide association study (n = 5619), and an epigenome-wide association study (n = 3743). We prioritized the significant genes with a machine learning-based method, netWAS, which borrows information from adipose tissue-specific interaction networks. We also used the brain-specific network in netWAS to investigate genes potentially involved in brain-adipose interaction. RESULTS: We identified 195 genes that were significantly associated with BMI through meta-analysis. The netWAS analysis narrowed down the list to 21 genes in adipose tissue. Among these 21 genes, six genes, including FUS, STX4, CCNT2, FUBP1, NDUFS3, and RAPSN, were not reported to be BMI-associated in PubMed or GWAS Catalog. We also identified 11 genes that were significantly associated with BMI in both adipose and whole brain tissues. CONCLUSION: This study integrated three types of omics data and identified a group of genes that have not previously been reported to be associated with BMI. This strategy could provide new insights for future studies to identify molecular mechanisms contributing to BMI regulation.

Different Risks of Mortality and Longitudinal Transition Trajectories in New Potential Subtypes of the Preserved Ratio Impaired Spirometry: Evidence From the English Longitudinal Study of Aging.

Background: Preserved ratio impaired spirometry (PRISm), characterized by the decreased forced expiratory volume in 1 s (FEV1) and forced vital capacity (FVC) with a preserved FEV1/FVC ratio, is highly prevalent and heterogeneous. We aimed to identify the subtypes of PRISm and examine their differences in clinical characteristics, long-term mortality risks, and longitudinal transition trajectories. Methods: A total of 6,616 eligible subjects were included from the English longitudinal study of aging. Two subtypes of the PRISm were identified as mild PRISm (either of FEV1 and FVC <80% predicted value, FEV1/FVC ≥0.7) and severe PRISm (both FEV1 and FVC <80% predicted values, FEV1/FVC ≥0.7). Normal spirometry was defined as both FEV1 and FVC ≥80% predicted values and FEV1/FVC ≥0.7. Hazard ratios (HRs) and 95% CIs were calculated by the multiple Cox regression models. Longitudinal transition trajectories were described with repeated spirometry data. Results: At baseline, severe PRISm had increased respiratory symptoms, including higher percentages of phlegm, wheezing, dyspnea, chronic bronchitis, and emphysema than mild PRISm. After an average of 7.7 years of follow-up, severe PRISm significantly increased the risks of all-cause mortality (HR=1.91, 95%CI = 1.58-2.31), respiratory mortality (HR = 6.02, 95%CI = 2.83-12.84), and CVD mortality (HR = 2.11, 95%CI = 1.42-3.13) compared with the normal spirometry, but no significantly increased risks were found for mild PRISm. In the two longitudinal transitions, mild PRISm tended to transition toward normal spirometry (40.2 and 54.7%), but severe PRISm tended to maintain the status (42.4 and 30.4%) or transition toward Global Initiative for Chronic Obstructive Lung Disease (GOLD)2-4 (28.3 and 33.9%). Conclusion: Two subtypes of PRISm were identified. Severe PRISm had increased respiratory symptoms, higher mortality risks, and a higher probability of progressing to GOLD2-4 than mild PRISm. These findings provided new evidence for the stratified management of PRISm.