Overall Abstract Background: Obesity is a major public health challenge worldwide and in Manitoba. An estimated 40-70% of obesity is heritable; however, these genetic associations are poorly investigated in the Manitoban adult population using the “gold standard” Dual Energy X-Ray Absorptiometry (DXA) to assess obesity phenotypes. The Manitoba Personalized Lifestyle Research (TMPLR) project enabled a genetic association study in middle-aged Manitobans. Obesity phenotypes considered are total, gynoid, android, arms, legs, and trunk fat mass. Objectives:

1. Perform a systematic review to determine genes associated with obesity phenotypes assessed by DXA in middle-aged cohorts.
2. Develop a “pipeline” to conduct Genome-Wide Association Studies (GWAS) within the TMPLR.
3. Conduct a GWAS on obesity phenotypes within TMPLR.
4. Compare the genes from the systematic review to those from TMPLR data analysis. Methods: The Covidence platform was used for the systematic review. Publications up to July 2023 sourced from Embase and Medline. The methods for the TMPLR project have been published. A GWAS pipeline was established using the Biodata Catalyst bioinformatics platform and the Seven Bridges R studio version 4.1. Results: Out of 94 and 25 studies obtained from Medline and Embase respectively, 14 studies met the eligibility criteria and 13 genes were identified that are associated with obesity-related phenotypes. No significant genome-wide association with obesity was established in the TMPLR cohort. However, 23 loci have had suggestive associations with the obesity phenotypes. Conclusion: There is a lack of high-quality genetic studies that use DXA data and adult populations. No genome-wide associations were reported in TMPLR, likely due to the limited sample size of the cohort. However, a bioinformatics pipeline to analyze genome-wide associations in TMPLR cohort is established and can be used for larger cohorts, such as UK biobanks.