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In collaboration with Northwestern Medicine investigators, an international multi-center study has identified genetic factors associated with SARS-CoV-2 infection and COVID-19 severity, according to findings published in Nature.

"So many groups and investigators banded together to make this phenomenal discovery a reality. This took the work of a global village," said Minoli Perera, PharmD, PhD, associate professor of Pharmacology, substitute for cymbalta member of the Robert H. Lurie Comprehensive Cancer Center of Northwestern University and a co-author of the study.

Genetics are instrumental in determining a person's susceptibility and responsiveness to viral infections, in conjunction with other environmental, clinical and social factors. In the case of SARS-CoV-2, the virus that causes COVID-19, identifying the precise role of human genetics could reveal critical insights into the development of the disease and the effectiveness of treatments, according to the authors.

For the current study, named the COVID-19 Host Genetics Initiative, Perera's laboratory collaborated with an international team of investigators to compile results from three genome-wide association meta-analyses. This data comprised more than 49,000 patients with COVID-19 from 46 studies across 19 different countries.

Perera is also the principal investigator of the African American Cardiovascular Pharmacogenomics Consortium (ACCOuNT), a group of healthcare providers, community leaders, and patients committed to accelerating pharmacogenomic discovery and translation in African-American patients. Perera's laboratory provided one of only six African-ancestry patient data cohorts for the study.

African and native populations are the least well represented in genomics. Even though there were over 200,000 participants in the study, our contribution was critical to the diversity in this study,"

Minoli Perera, PharmD, PhD, Study Co-Author and Associate Professor, Pharmacology, Northwestern University

Using this data, the investigators mapped the human genome for genetic variants associated with COVID-19 severity and susceptibility and identified 13 genome-wide genetic markers that were found to be associated with SARS-CoV-2 infection or more severe manifestations of COVID-19.

This included variants located on chromosome three and in the genes CXCR6 — which is known to be important in chemokine signaling, a process essential for coordinated cell migration in disease — and SLC6A20 —an amino acid transporter that interacts with the ACE2 receptor, promoting COVID-19 infection. According to the authors, many of the identified variants have previously been associated with autoimmune or inflammatory diseases. Additional analyses also revealed an association between smoking and body mass index for severe COVID-19.

While there is potential for the identified pathways to aid in the development of new therapies, Perera said it's still too soon to tell and additional research is warranted.