Study: Genome-wide Association Study of Long COVID (pre-print)
Overview: This study is a meta-analysis of other genome-wide studies, combining the data to analyze over 6,000 long Covid patients compared with over 1,000,000 controls.
Genome-wide association studies take an agnostic approach to see if any area of the genome differs from the normal. In this case, they were comparing the whole genome data from people with confirmed long Covid to the genetic data of people without long Covid. These studies take a massive amount of data and computing power in order to detect signals related to the pathways involved in a disease.
The study showed that the FOXP4 gene was statistically likely to be involved in long Covid.
Background: FOXP4 gene encodes the protein Forkhead Box P4, which is a transcription factor. It is found in tissues throughout the body, including in lung tissue. Other variants in FOXP4 are linked to a slight increase in the relative risk of lung cancer.
FOXP4 is important in the regulation of fetal developmental processes, including the development of the central nervous system, lungs, and gut. Loss of function mutations are linked to neurodevelopmental disorders and congenital abnormalities in children.[ref] In adults, FOXP4 is thought to regulate growth in cancer cells, as well as impact T cell function. Overexpression of FOXP4 is linked to prostate cancer and lung cancer.[ref] Additionally, FOXP4 has recently been found to be expressed in fat cells and linked to UCP1, which regulates thermogenesis (heat production in brown fat).[ref]
According to the authors of the meta-analysis GWAS, the long Covid FOXP4 variant is likely to be a gain-of-function variant.