A state-based approach to genomics for rare disease and population screening

Abstract

Purpose

The Alabama Genomic Health Initiative (AGHI) is a state-funded effort to provide genomic testing. AGHI engages two distinct cohorts across the state of Alabama. One cohort includes children and adults with undiagnosed rare disease; a second includes an unselected adult population. Here we describe findings from the first 176 rare disease and 5369 population cohort AGHI participants.

Methods

AGHI participants enroll in one of two arms of a research protocol that provides access to genomic testing results and biobank participation. Rare disease cohort participants receive genome sequencing to identify primary and secondary findings. Population cohort participants receive genotyping to identify pathogenic and likely pathogenic variants for actionable conditions.

Results

Within the rare disease cohort, genome sequencing identified likely pathogenic or pathogenic variation in 20% of affected individuals. Within the population cohort, 1.5% of individuals received a positive genotyping result. The rate of genotyping results corroborated by reported personal or family history varied by gene.

Conclusions

AGHI demonstrates the ability to provide useful health information in two contexts: rare undiagnosed disease and population screening. This utility should motivate continued exploration of ways in which emerging genomic technologies might benefit broad populations.

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Data availability

The data that support the findings of this study are available from the corresponding author (K.M.E.). Global screening array identified and Sanger confirmed P/LP variants have been submitted to ClinVar (searchable by study IDs: AGHI_GT and AGHI_WGS).

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Acknowledgements

We thank the AGHI participants for their contributions to this study. This study was supported by funding from the State of Alabama. This study was also supported by the UAB Center for Clinical and Translational Science, funded by a National Institutes of Health (NIH) Clinical and Translational Science Award (CTSA) grant (UL1TR003096).

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Contributions

Conceptualization: K.M.E., W.V.K., A.C., T.M., G.M.C., M.M., G.S.B., B.R.K.; Data curation: K.M.E., W.V.K., A.C., M.E.C., I.P.M., K.M.B., M.L.T., R.D.J.; Formal Analysis: K.M.E, W.V.K., A.C., M.E.C, I.P.M., K.M.B., M.L.T., R.D.J.; Funding acquisition: I.P.M., G.M.C., M.M., G.S.B., B.R.K.; Investigation: W.V.K., M.E.C., I.P.M., A.C.E.H., K.M.B., M.L.T., E.M.B.; Methodology: K.M.E., W.V.K., A.C., I.P.M., T.M., M.N.O., S.O.S., J.C.E., J.J.C., M.F., W.A.C., A.C.E.H., G.M.C., M.M., G.S.B., B.R.K.; Project Administration: I.P.M., Supervision: G.M.C., M.M., G.S.B., B.R.K.; Writing – original draft: K.M.E., W.V.K., A.C., M.E.C.; Writing– review & editing: K.M.E, W.V.K., A.C., M.E.C, I.P.M, T.M., M.N.O., S.O.S., J.C.E., J.J.C, M.F., W.A.C., A.C.E.H., K.M.B., M.L.T., E.M.B., R.D.J., G.M.C, M.M., G.S.B., B.R.K.

Corresponding author

Correspondence to Kelly M. East MS.

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Competing interests

The authors declare no conflicts of interest.

Ethics declaration

The Alabama Genomic Health Initiative was reviewed and approved by the UAB Institutional Review Board (protocol number F170303004). Informed consent was obtained from all participants.

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East, K.M., Kelley, W.V., Cannon, A. et al. A state-based approach to genomics for rare disease and population screening. Genet Med (2020). https://doi.org/10.1038/s41436-020-01034-4

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