Dataset Information

Clinical experience with carrier screening in a general population: support for a comprehensive pan-ethnic approach.

ABSTRACT:

Purpose

To present results from a large cohort of individuals receiving expanded carrier screening (CS) in the United States.

Methods

Single-gene disorder carrier status for 381,014 individuals was determined using next-generation sequencing (NGS) based CS for up to 274 genes. Detection rates were compared with literature-reported values derived from disease prevalence and carrier frequencies. Combined theoretical affected pregnancy rates for the 274 screened disorders were calculated.

Results

For Ashkenazi Jewish (AJ) diseases, 81.6% (4434/5435) of carriers identified did not report AJ ancestry. For cystic fibrosis, 44.0% (6260/14,229) of carriers identified had a variant not on the standard genotyping panel. Individuals at risk of being a silent spinal muscular atrophy carrier, not detectable by standard screening, comprised 1/39 (8763/344,407) individuals. For fragile X syndrome, compared with standard premutation screening, AGG interruption analysis modified risk in 83.2% (1128/1356) premutation carriers. Assuming random pairing across the study population, approximately 1/175 pregnancies would be affected by a disorder in the 274-gene screening panel.

Conclusion

Compared with standard screening, NGS-based CS provides additional information that may impact reproductive choices. Pan-ethnic CS leads to substantially increased identification of at-risk couples. These data support offering NGS-based CS to all reproductive-aged women.

SUBMITTER: Westemeyer M

PROVIDER: S-EPMC7394882 | biostudies-literature | 2020 Aug

REPOSITORIES: biostudies-literature

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Publications

Clinical experience with carrier screening in a general population: support for a comprehensive pan-ethnic approach.

Westemeyer Maggie M Saucier Jennifer J Wallace Jody J Prins Sarah A SA Shetty Aparna A Malhotra Meenakshi M Demko Zachary P ZP Eng Christine M CM Weckstein Louis L Boostanfar Robert R Rabinowitz Matthew M Benn Peter P Keen-Kim Dianne D Billings Paul P

Genetics in medicine : official journal of the American College of Medical Genetics 20200505 8

<h4>Purpose</h4>To present results from a large cohort of individuals receiving expanded carrier screening (CS) in the United States.<h4>Methods</h4>Single-gene disorder carrier status for 381,014 individuals was determined using next-generation sequencing (NGS) based CS for up to 274 genes. Detection rates were compared with literature-reported values derived from disease prevalence and carrier frequencies. Combined theoretical affected pregnancy rates for the 274 screened disorders were calcul ...[more]

PMID: 32366966

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Project description:IntroductionFragile X syndrome (FXS) is the leading cause of inherited intellectual and developmental disability. Policy development relating to carrier screening programmes for FXS requires input from large studies examining not only test uptake but also psychosocial aspects. This study will compare carrier screening in pregnant and non-pregnant populations, examining informed decision-making, psychosocial issues and health economics.Methods and analysisPregnant and non-pregnant women are being recruited from general practices and obstetric services. Women receive study information either in person or through clinic mail outs. Women are provided pretest counselling by a genetic counsellor and make a decision about testing in their own time. Data are being collected from two questionnaires: one completed at the time of making the decision about testing and the second 1 month later. Additional data are gathered through qualitative interviews conducted at several time points with a subset of participating women, including all women with a positive test result, and with staff from recruiting clinics. A minimum sample size of 500 women/group has been calculated to give us 88% power to detect a 10% difference in test uptake and 87% power to detect a 10% difference in informed choice between the pregnant and non-pregnant groups. Questionnaire data will be analysed using descriptive statistics and multivariate logistic regression models. Interview data will be thematically analysed. Willingness-to-pay and cost effectiveness analyses will also be performed. Recruitment started in July 2009 and data collection will be completed by December 2013.Ethics and disseminationEthics approval has been granted by the Universities of Melbourne and Western Australia and by recruiting clinics, where required. Results will be reported in peer-reviewed publications, conference presentations and through a website http://www.fragilexscreening.net.au. The results of this study will make a significant contribution to discussions about the wider introduction of population carrier screening for FXS.

Dataset Information

Clinical experience with carrier screening in a general population: support for a comprehensive pan-ethnic approach.

Purpose

Methods

Results

Conclusion

Publications

Clinical experience with carrier screening in a general population: support for a comprehensive pan-ethnic approach.

Similar Datasets

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