genetic correlations between covid 19 and a variety of diseases and other medically CORD-Papers-2021-10-25 (Version 1)

Title: Genetic correlations between COVID-19 and a variety of diseases and other medically relevant traits
Abstract: We analyzed GWAS results released by COVID-19 Host Genetics Initiative, UK biobank and GWAS Catalog to explore the genetic overlap between COVID-19 and a broad spectrum of traits and diseases. We validate previously reported medical conditions and risk factors based on epidemiological studies, including but not limited to hypertension, type 2 diabetes and obesity. We also report novel traits associated with COVID-19, which have not been previously reported from epidemiological data, such as opioid use and educational attainment. Taken together, this study extends our understanding of the genetic basis of COVID-19, and provides target traits for further epidemiological studies.
Published: 12/20/2020
DOI: 10.1101/2020.12.18.20248319
DOI_URL: http://doi.org/10.1101/2020.12.18.20248319
Author Name: Chang, X
Author link: https://covid19-data.nist.gov/pid/rest/local/author/chang_x
Author Name: Li, Y
Author link: https://covid19-data.nist.gov/pid/rest/local/author/li_y
Author Name: Nguyen, K
Author link: https://covid19-data.nist.gov/pid/rest/local/author/nguyen_k
Author Name: Qu, H
Author link: https://covid19-data.nist.gov/pid/rest/local/author/qu_h
Author Name: Liu, Y
Author link: https://covid19-data.nist.gov/pid/rest/local/author/liu_y
Author Name: Glessner, J
Author link: https://covid19-data.nist.gov/pid/rest/local/author/glessner_j
Author Name: Sleiman, P
Author link: https://covid19-data.nist.gov/pid/rest/local/author/sleiman_p
Author Name: Hakonarson, H
Author link: https://covid19-data.nist.gov/pid/rest/local/author/hakonarson_h
sha: 58b0df922272ec01437d3ffc7a8448c715e48cd2
license: medrxiv
source_x: MedRxiv; WHO
source_x_url: https://www.who.int/
url: http://medrxiv.org/cgi/content/short/2020.12.18.20248319v1?rss=1 https://doi.org/10.1101/2020.12.18.20248319
has_full_text: TRUE
Keywords Extracted from Text Content: COVID-19 COVID-19 Host UK biobank COVID-19 COVID-19 Host gastro-oesophageal reflux disease Patients COVID-19 Host Genetics Initiative 3 LD score regression (LDSC) Neale lab × 10 -5 digestive patients https://doi.org/10.1101/2020.12.18.20248319 doi B2_ALL brain opioids × × 10 A2_ALL peptic ulcer medRxiv preprint PMID Coronary artery UK B2_ALL_eur HapMap3 C2_ALL_eur Catalog 4 Tramadol pulmonary coronavirus disease 2019 connective tissue COVID-19 1 medRxiv UK biobank opioid COVID-19 2 human heart http://www.nealelab.is/uk-biobank/
Extracted Text Content in Record: First 5000 Characters:#Contributed equally to this work. We analyzed GWAS results released by COVID-19 Host Genetics Initiative, UK biobank and GWAS Catalog to explore the genetic overlap between COVID-19 and a broad spectrum of traits and diseases. We validate previously reported medical conditions and risk factors based on epidemiological studies, including but not limited to hypertension, type 2 diabetes and obesity. The ongoing coronavirus disease 2019 (COVID-19) break has posed an extraordinary threat to global public health. Patients with certain underlying medical conditions such as obesity, hypertension, and diabetes are at increased risk for poor outcome in COVID-19 1 . Given high genetic heritability of the aforementioned conditions, their shared genetic factors may play a crucial role in the severity of COVID-19. Indeed, a recent genome-wide association study (GWAS) of COVID-19 has reported two genomic loci associated with severe COVID-19, indicating a strong genetic influence on the severity of COVID-19 2 . Here, we analyzed GWAS results released by COVID-19 Host Genetics Initiative 3 , UK biobank and GWAS Catalog to explore the genetic overlap between COVID-19 and a broad spectrum of traits and diseases. Summary statistics of selected COVID-19 GWAS (sample size > 30,000 and percentage of Europeans > 90%) were downloaded from COVID-19 Host Genetics Initiative including A2_ALL (very severe respiratory confirmed COVID-19 against population), B2_ALL (hospitalized COVID-19 against population), B2_ALL_eur (hospitalized COVID-19 against population in Europeans), C2_ALL_eur (COVID-19 against population in Europeans). GWAS summary statistics of selected diseases/traits were downloaded from UK biobank and GWAS Catalog 4 . Genetic correlation r g between COVID-19 and interested diseases/traits were estimated by LD score regression (LDSC) using GWAS summary statistics that overlap with HapMap3 SNPs as recommended 5 . Pre-computed linkage disequilibrium scores for HapMap3 SNPs calculated based on European-ancestry individuals from the 1000 Genomes Project were used in the analysis. We first investigated genetic correlations between COVID-19 and 1555 diseases/traits from the analysis of UK biobank data by Neale lab (http://www.nealelab.is/uk-biobank/). Our results are consistent with the epidemiological observation that BMI is significantly associated with severe or hospitalized COVID-19 (A2_ALL, rg = 0.24, P = 3.35 × 10 -6 ; B2_ALL, rg = 0.39, P = 3.33 × 10 -7 ). COPD (chronic obstructive pulmonary disease), heart diseases, hypertension, diabetes and smoking status exhibit substantial magnitude of genetic correlation with COVID-19, though statistical significance do not pass the strict threshold after adjustment for multiple testing (Table 1) . Collectively, diseases of the circulatory system, diseases of the digestive system, and diseases of the musculoskeletal system and connective tissue are significantly associated with severe or hospitalized COVID-19 (Table 1 ). In agreement with this, a number of medication-taking traits linked to obesity, diabetes, hypertension and digestion display modest correlation with COVID-19 (Table 1) . Tramadol, an opioid pain medication, is significantly correlated with hospitalized COVID-19 (B2_ALL, rg = 0.65, P = 1.26 × 10 -5 ). Interestingly, our results indicated a significant negative correlation between severe or hospitalized COVID-19 and educational attainment related traits including college or university degree (A2_ALL, rg = -0.24, P = 8.51 × 10 -7 ; B2_ALL, rg = -0.32, P = 1.78 × 10 -6 ) and fluid intelligence score (A2_ALL, rg = -0.25, P = 2.40 × 10 -5 ; B2_ALL, rg = -0.26, P = 7.66 × 10 -5 ). Hospitalized COVID-19 (B2_ALL, rg = 0.73, P = 8.60 × 10 -6 ) is also significantly correlated with panic attacks. . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review) preprint The copyright holder for this this version posted December 20, 2020. ; https://doi.org/10.1101/2020.12.18.20248319 doi: medRxiv preprint We next estimated genetic correlations between COVID-19 and 80 diseases/traits from GWAS Catalog 4 . Consistently, hypertension, type 2 diabetes and obesity are significantly associated with severe or hospitalized COVID-19 (Table 2) . Coronary artery disease, heart failure and BMI are also modestly associated with severe COVID-19. Likewise, medication-taking traits related to obesity, diabetes, hypertension and digestion are modestly associated with COVID-19 such as drugs for diabetes, and antihypertensives ( Table 2 ). Significant correlations are also found between hospitalized COVID-19 and drugs for peptic ulcer and gastro-oesophageal reflux disease (B2_ALL, rg = 0.34, P = 3.01 × 10 -5 ; B2_ALL_eur, rg = 0.28, P = 0.0006), diuretic use and very severe respiratory confirmed COVID-19 (A2_ALL, rg = 0.25, P = 0.0002), opioids and severe or
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