Effects of smoking on the genetic risk of obesity: the population architecture using genomics and epidemiology study

<p>Abstract</p> <p>Background</p> <p>Although smoking behavior is known to affect body mass index (BMI), the potential for smoking to influence genetic associations with BMI is largely unexplored.</p> <p>Methods</p> <p>As part of the ‘Population Architecture using Genomics and Epidemiology (PAGE)’ Consortium, we investigated interaction between genetic risk factors associated with BMI and smoking for 10 single nucleotide polymorphisms (SNPs) previously identified in genome-wide association studies. We included 6 studies with a total of 56,466 subjects (16,750 African Americans (AA) and 39,716 European Americans (EA)). We assessed effect modification by testing an interaction term for each SNP and smoking (current vs. former/never) in the linear regression and by stratified analyses.</p> <p>Results</p> <p>We did not observe strong evidence for interactions and only observed two interactions with p-values <0.1: for rs6548238/<it>TMEM18</it>, the risk allele (C) was associated with BMI only among AA females who were former/never smokers (β = 0.018, p = 0.002), vs. current smokers (β = 0.001, p = 0.95, p_interaction = 0.10). For rs9939609/<it>FTO</it>, the A allele was more strongly associated with BMI among current smoker EA females (β = 0.017, p = 3.5x10^-5), vs. former/never smokers (β = 0.006, p = 0.05, p_interaction = 0.08).</p> <p>Conclusions</p> <p>These analyses provide limited evidence that smoking status may modify genetic effects of previously identified genetic risk factors for BMI. Larger studies are needed to follow up our results.</p> <p>Clinical Trial Registration</p> <p>NCT00000611</p

Mapping the human genetic architecture of COVID-19

The genetic make-up of an individual contributes to the susceptibility and response to viral infection. Although environmental, clinical and social factors have a role in the chance of exposure to SARS-CoV-2 and the severity of COVID-191,2, host genetics may also be important. Identifying host-specific genetic factors may reveal biological mechanisms of therapeutic relevance and clarify causal relationships of modifiable environmental risk factors for SARS-CoV-2 infection and outcomes. We formed a global network of researchers to investigate the role of human genetics in SARS-CoV-2 infection and COVID-19 severity. Here we describe the results of three genome-wide association meta-analyses that consist of up to 49,562 patients with COVID-19 from 46 studies across 19 countries. We report 13 genome-wide significant loci that are associated with SARS-CoV-2 infection or severe manifestations of COVID-19. Several of these loci correspond to previously documented associations to lung or autoimmune and inflammatory diseases3–7. They also represent potentially actionable mechanisms in response to infection. Mendelian randomization analyses support a causal role for smoking and body-mass index for severe COVID-19 although not for type II diabetes. The identification of novel host genetic factors associated with COVID-19 was made possible by the community of human genetics researchers coming together to prioritize the sharing of data, results, resources and analytical frameworks. This working model of international collaboration underscores what is possible for future genetic discoveries in emerging pandemics, or indeed for any complex human disease