Dataset Information

A catalog of associations between rare coding variants and COVID-19 outcomes.

ABSTRACT: Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) causes coronavirus disease-19 (COVID-19), a respiratory illness that can result in hospitalization or death. We investigated associations between rare genetic variants and seven COVID-19 outcomes in 543,213 individuals, including 8,248 with COVID-19. After accounting for multiple testing, we did not identify any clear associations with rare variants either exome-wide or when specifically focusing on (i) 14 interferon pathway genes in which rare deleterious variants have been reported in severe COVID-19 patients; (ii) 167 genes located in COVID-19 GWAS risk loci; or (iii) 32 additional genes of immunologic relevance and/or therapeutic potential. Our analyses indicate there are no significant associations with rare protein-coding variants with detectable effect sizes at our current sample sizes. Analyses will be updated as additional data become available, with results publicly browsable at https://rgc-covid19.regeneron.com .

SUBMITTER: Kosmicki JA

PROVIDER: S-EPMC7924298 | biostudies-literature | 2021 Feb

REPOSITORIES: biostudies-literature

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A catalog of associations between rare coding variants and COVID-19 outcomes.

Kosmicki J A JA Horowitz J E JE Banerjee N N Lanche R R Marcketta A A Maxwell E E Bai X X Sun D D Backman J D JD Sharma D D Kang H M HM O'Dushlaine C C Yadav A A Mansfield A J AJ Li A H AH Watanabe K K Gurski L L McCarthy S E SE Locke A E AE Khalid S S O'Keeffe S S Mbatchou J J Chazara O O Huang Y Y Kvikstad E E O'Neill A A Nioi P P Parker M M MM Petrovski S S Runz H H Szustakowski J D JD Wang Q Q Wong E E Cordova-Palomera A A Smith E N EN Szalma S S Zheng X X Esmaeeli S S Davis J W JW Lai Y-P YP Chen X X Justice A E AE Leader J B JB Mirshahi T T Carey D J DJ Verma A A Sirugo G G Ritchie M D MD Rader D J DJ Povysil G G Goldstein D B DB Kiryluk K K Pairo-Castineira E E Rawlik K K Pasko D D Walker S S Meynert A A Kousathanas A A Moutsianas L L Tenesa A A Caulfield M M Scott R R Wilson J F JF Baillie J K JK Butler-Laporte G G Nakanishi T T Lathrop M M Richards J B JB Jones M M Balasubramanian S S Salerno W W Shuldiner A R AR Marchini J J Overton J D JD Habegger L L Cantor M N MN Reid J G JG Baras A A Abecasis G R GR Ferreira M A MA

medRxiv : the preprint server for health sciences 20210227

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) causes coronavirus disease-19 (COVID-19), a respiratory illness that can result in hospitalization or death. We investigated associations between rare genetic variants and seven COVID-19 outcomes in 543,213 individuals, including 8,248 with COVID-19. After accounting for multiple testing, we did not identify any clear associations with rare variants either exome-wide or when specifically focusing on (i) 14 interferon pathway genes in w ...[more]

PMID: 33655273

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Project description:BackgroundLarge-scale evaluation of COVID-19 is likely to rely on the quality of ICD coding. However, little is known about the validity of ICD-coded COVID-19 diagnoses.ObjectivesTo evaluate the performance of diagnostic codes in detecting COVID-19 during pregnancy.MethodsWe used data from a national cohort of 78,283 individuals with a pregnancy ending between 11 March 2020 and 31 January 2021 in the OptumLabs® Data Warehouse (OLDW). OLDW is a longitudinal, real-world data asset with de-identified administrative claims and electronic health record data. We identified all services with an ICD-10-CM diagnostic code of U07.1 and all laboratory claims records for COVID-19 diagnostic testing. We compared ICD-coded diagnoses to testing results to estimate positive and negative predictive values (PPV and NPV). To evaluate impact on risk estimation, we estimated risk of adverse pregnancy outcomes by source of exposure information.ResultsOf 78,283 pregnancies, 5644 had a laboratory test result for COVID-19. Testing was most common among older individuals, Hispanic individuals, those with higher socioeconomic status and those with a diagnosed medical condition or pregnancy complication; 52% of COVID-19 cases was identified through ICD-coded diagnosis alone, 19% from laboratory test results alone and 29% from both sources. Agreement between ICD-coded diagnosis and laboratory testing records was high 91% (95% confidence interval [CI] 90, 92). However, the PPV of ICD-code diagnosis was low (36%; 95% CI 33, 39). We observed up to a 50% difference in risk estimates of adverse pregnancy outcomes when exposure was based on laboratory testing results or diagnostic coding alone.ConclusionsMore than one-in-five COVID-19 cases would be missed by using ICD-coded diagnoses alone to identify COVID-19 during pregnancy. Epidemiological studies exclusively relying on diagnostic coding or laboratory testing results are likely to be affected by exposure misclassification. Research and surveillance should draw upon multiple sources of COVID-19 diagnostic information.

Dataset Information

A catalog of associations between rare coding variants and COVID-19 outcomes.

Publications

A catalog of associations between rare coding variants and COVID-19 outcomes.

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