Submitted by sjc313 on Fri, 06/06/2025 - 08:34
Michael Inouye, Cardiovascular Epidemiology Unit, Department of Public Health and Primary Care
The complete blood count is amongst the most routinely ordered clinical laboratory tests performed globally. The levels of blood cell traits frequently inform clinical decision making and are strongly affected by genetics; however, the role of genetics in controlling the variance of blood cell traits is largely unexplored. Using the INTERVAL study and UK Biobank, this study uncovered 176 independent alleles (vQTLs) affecting variance of one or more of 29 blood cell traits, the vast majority of which were not involved in trait levels. These vQTLs were under strong negative selective pressure, greater than that of alleles for trait levels. Polygenic scores for blood cell trait variances were constructed and used to find population strata in which conventional polygenic scores had significantly improved performance. Finally, using Mendelian randomisation, it was found that alcohol consumption generally increased blood cell trait variances, particularly for corpuscular haemoglobin concentration and corpuscular volume variance, red blood cell count and neutrophil percentage of white blood cells.
Read the paper here: Genome-wide analyses of variance in blood cell phenotypes provide new insights into complex trait biology and prediction