A study in which authors used the genetic effects of body mass index (BMI) and cholesterol on hemoglobin level (HGB) to infer casual relationships, propose genetic mechanisms, and identify relevant cell types was presented at the 63rd ASH Annual Meeting & Exposition.

According to authors of the study, they found a 5 kg/m² (1 standard deviation unit) increase in BMI decreased hemoglobin by 0.06±0.01 g/dL (p=1x10^-5 ) using a mendelian randomization (MR) framework.

“Increased BMI also decreased erythrocyte count, and unexpectedly also decreased platelet and white blood cell counts (all with p<5x10^-3),” stated authors of the study. “These data showed that obesity-related mechanisms extended beyond the erythroid lineage, perhaps impacting multipotent hematopoietic progenitor cells (HPCs).”

Results of the study showed that a 1 SD unit increase in total cholesterol decreased hemoglobin level (HGB). According to authors of the study, genetic effects of cholesterol were restricted to erythroid traits such as HGB and hematocrit.

“Multivariable and mediation analyses confirmed that effects of BMI and cholesterol functioned through distinct genetic mechanisms,” stated authors of the study.

An unexpectant result according to authors of the study, was that “increased waist-hip ratio (WHR) in contrast to BMI increased HGB (0.08±0.02 g/dL, p=9x10^-6) as well as erythrocyte, platelet, and white blood cell counts (all with p<4x10^-3).”

Results showed that obesity impacts blood traits through genetically determined adipose distribution.

Authors said results were consistent with clinical observations to confirm that BMI and cholesterol negatively impact HGB at a genetic level.

“The unexpected multilineage effects of genetically determined BMI most likely reflects a tendency to accumulate bone marrow adipose tissue, which in turn impacts HPCs and downstream blood cell production,” concluded authors of the study. “Our findings suggest that adjustment for BMI and adiposity traits may be considered in blood trait [genome wide association studies] analyses and illuminate opportunities to functionally dissect related genes and molecular pathways.”

Reference:
Thom C, Wilken M, Chou ST, Voight BF. Genetically determined obesity and adipose distribution impact human blood trait variation across cell lineages. Poster presented at: 63rd ASH Annual Meeting & Exposition; December 11-14, 2021; Atlanta, GA.