(P10-019-23) Impact of Genetically Predicted Circulating Choline Levels on Health Outcomes: A Scoping Review

Objectives: Conduct a scoping review to assess the impact of genetic polymorphisms on circulating choline and choline-related metabolite levels, and subsequent associations with health outcomes.

Methods: This study follows the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement scoping review extension. Literature was searched to 9/28/2022 in four databases: Embase, Medline, Web of Science, and the Biological Science Index. Studies of any duration in humans were considered. Any genome-wide association study (GWAS) investigating genetic variant associations with circulating choline and/or choline-related metabolites, and any Mendelian randomization (MR) study investigating the association of genetically predicted circulating choline and/or choline-related metabolites with any health outcome were considered. Qualitative evidence is presented in summary tables.

Results: From 1,211 total reviewed articles, 33 were included (GWAS = 7; MR = 26). GWAS results: Twenty-five circulating choline-related metabolites were significantly associated with genetic variants in GWAS studies: primarily TMAO, betaine, sphingomyelins, lysophosphatidylcholines, and phosphatidylcholines. MR results: MR studies investigated associations between 52 total unique choline metabolites and 66 unique health outcomes. Of these, 47 significant associations were reported between 16 metabolites (primarily choline, lysophosphatidylcholines, phosphatidylcholines, betaine, and sphingomyelins) and 27 health outcomes including cancer, cardiovascular, metabolic, bone, and brain-related outcomes. Some articles reported significant associations between multiple choline types and the same health outcome.

Conclusions: Genetically predicted circulating choline and choline-related metabolite levels significantly impact a wide variety of health outcomes. Further research is needed to assess how genetic variability influences choline metabolism, and whether individuals with lower genetically predicted circulating choline and choline-related metabolite levels would benefit from a dietary intervention or supplementation.

Funding Sources: Investigator-initiated unrestricted educational grant from the Egg Nutrition Center.