Population Health Genetic Screening for Tier 1 Inherited Diseases in Northern Nevada: 90% of At-Risk Carriers are Missed

Grzymski, J.; Elhanan, G.; Smith, E.; Rowan, C.; Slotnick, N.; Dabe, S.; Schlauch, K.; Read, R.; Metcalf, J.; Lipp, B.; Reed, H.; Levin, E.; Kao, J.; Rashkin, M.; Bowes, J.; Bolze, A.; Dunaway, K.; Washington, N.; Slonim, A.; Lu, J. T.

doi:10.1101/650549

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bioRxiv · 10.1101/650549

Population Health Genetic Screening for Tier 1 Inherited Diseases in Northern Nevada: 90% of At-Risk Carriers are Missed

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Abstract

In an unselected population of 23,713 participants who underwent clinical exome sequencing as a part of the Healthy Nevada Project (HNP) in Northern Nevada (Renown Health, Reno, Nevada) from March 15, 2018, to Sept 30, 2018 (Table S1) we find a 1.26% carrier rate for expected pathogenic and likely pathogenic genetic variants in (FH: LDLR, PCSK9, APOB), Hereditary Breast and Ovarian Cancer (HBOC: BRCA1, BRCA2) and Lynch Syndrome (LS: MLH1, MSH2, MSH6, PSM2) with over 90% of carriers undetected under current medical practice. 26% of carriers were found to have advanced disease with 70% first diagnosed before the age of 65. Less than 20% of all carriers had any documented suspicion for inherited genetic disease in the medical record and upon direct follow-up survey under 40% of carriers had family history of relevant disease. A population preventative genetic screening approach for patients under 45 may improve outcomes.\n\nO_TBL View this table:\norg.highwire.dtl.DTLVardef@1eb1896org.highwire.dtl.DTLVardef@19b2a11org.highwire.dtl.DTLVardef@1e6da81org.highwire.dtl.DTLVardef@1138699org.highwire.dtl.DTLVardef@e9c415_HPS_FORMAT_FIGEXP M_TBL O_FLOATNOTable S1:C_FLOATNO O_TABLECAPTIONDemographic Profile of Healthy Nevada Project Participants.\n\nC_TABLECAPTION C_TBL

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Grzymski, J., Elhanan, G., Smith, E., Rowan, C., Slotnick, N., Dabe, S., Schlauch, K., Read, R., Metcalf, J., Lipp, B., Reed, H., Levin, E., Kao, J., Rashkin, M., Bowes, J., Bolze, A., Dunaway, K., Washington, N., Slonim, A., Lu, J. T.. 2019-05-27. Population Health Genetic Screening for Tier 1 Inherited Diseases in Northern Nevada: 90% of At-Risk Carriers are Missed. https://doi.org/10.1101/650549

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