Date of Award
1-1-2021
Document Type
Open Access Thesis
Degree Name
Master of Public Health (MPH)
Department
School of Public Health
First Advisor
Yasmmyn D. Salinas
Abstract
Genetic data suggest that obesity and inflammation shared a portion of their genetic architectures. Meanwhile, epidemiologic data suggest a causal link between obesity and inflammation. Therefore, we hypothesized that there are variants in the human genome that display pleiotropy for obesity and inflammation and that the effects of at least some of those variants could be mediated by obesity-related pathways. To test these hypotheses, we conducted univariate genome-wide association analyses of obesity-related traits (BMI and WHRadjBMI) and inflammation (CRP) in the UK Biobank (n= 291,396 Caucasian subjects), searched for overlapping signals, fine-mapped the regions to identify putative causal SNPs, and decomposed the total genetic effects of the SNPs using causal mediation analyses, with an adjustment of confounding of the obesity-inflammation relationship. We identified 16 SNPs (rs79113395, rs58048722, rs199956414, rs12203592, rs2049870, rs2721966, rs10086741, rs179444, rs3808478, rs6265, rs7926362, rs4922793, rs4755725, rs12577464, rs8047395 and rs11075987), residing in 8 distinct genetic loci, that display pleiotropy for CRP and BMI and 1 SNP (rs429358) that displays pleiotropy for CRP and WHRadjBMI. Among these SNPs, 4 (rs58048722, rs199956414, rs4755725, rs12577464) affected CRP only through obesity-related pathways. All other SNPs had both direct effects on CRP and indirect effects through obesity-related pathways. We found insufficient evidence that the indirect effects of SNPs on CRP through our obesity measures were moderated by sex, despite of sex differences in the phenotypic relationship between these two traits. These identified SNPs lays the foundation for mechanistically understanding the pathogenesis of obesity- and inflammation-associated diseases and may serve as targets for therapies that simultaneously treat these conditions.
Recommended Citation
Wenren, Yiqian, "Discovery Of Genetic Pleiotropy For Obesity And Inflammation And Mediation In Identified Variants Through Obesity-Related Pathways" (2021). Public Health Theses. 2111.
https://elischolar.library.yale.edu/ysphtdl/2111
