Population screening shows risk of inherited cancer and familial hypercholesterolemia in Oregon

O’Brien, Timothy D.; Potter, Amiee B.; Driscoll, Catherine C.; Goh, Gregory; Letaw, John H.; McCabe, Sarah; Thanner, Jane; Kulkarni, Arpita; Wong, Rossana; Medica, Samuel; Week, Tiana; Buitrago, Jacob; Larson, Aaron; Camacho, Katie Johnson; Brown, Kim; Crist, Rachel; Conrad, Casey; Evans-Dutson, Sara; Lutz, Ryan; Mitchell, Asia; Anur, Pavana; Serrato, Vanessa; Shafer, Autumn; Marriott, Lisa K.; Hamman, K.J.; Mulford, Amelia; Wiszniewski, Wojciech; Sampson, Jone E.; Adey, Andrew; O’Roak, Brian J.; Harrington, Christina A.; Shannon, Jackilen; Spellman, Paul T.; Richards, C. Sue

doi:10.1016/j.ajhg.2023.06.014

Cited by 7 publications

(9 citation statements)

References 48 publications

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“…P/LP variants in LDLR were identified in 0.3% of participants which is similar to the carrier frequency found in our study population. 22 For the P/LP variants identified by us, 25.0% were predicted to be null variants. Null variants (ie, nonsense, frameshift, canonical splice site) result in premature stop codons with nonsense-mediated decay, resulting in no functional protein being produced.…”

Section: Discussionmentioning

confidence: 83%

“…In their study, 98% of participants were described as White and there was a substantial Amish component. 21 O’Brien et al, 22 offered community-based screening in Oregon for a panel of genes, including LDLR , at no cost to participants, 84% of whom self-identified as White people. Successful next-generation sequencing was performed on 13 760 samples.…”

Section: Discussionmentioning

confidence: 99%

“…P/LP variants in LDLR were identified in 0.3% of participants which is similar to the carrier frequency found in our study population. 22 …”

Section: Discussionmentioning

confidence: 99%

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Reproductive Carrier Screening: Identifying Families at Risk for Familial Hypercholesterolemia in the United States

Souter,

Becraft,

Brummitt

et al. 2024

Circ: Genomic and Precision Medicine

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BACKGROUND: Familial hypercholesterolemia is a treatable genetic condition but remains underdiagnosed. We reviewed the frequency of pathogenic or likely pathogenic (P/LP) variants in the LDLR gene in female individuals receiving reproductive carrier screening. METHODS: This retrospective observational study included samples from female patients (aged 18–55 years) receiving a 274-gene carrier screening panel from January 2020 to September 2022. LDLR exons and their 10 base pairs flanking regions were sequenced. Carrier frequency for P/LP variants was calculated for the entire population and by race/ethnicity. The most common variants and their likely functional effects were evaluated. RESULTS: A total of 91 637 tests were performed on women identifying as Asian (8.8%), Black (6.1%), Hispanic (8.5%), White (29.0%), multiple or other race/ethnicity (15.0%), and missing (33.0%). Median age was 32.8 years with 83 728 (91%) <40 years. P/LP LDLR variants were identified in 283 samples (1 in 324). No patients were identified with >1 P/LP variant. LDLR carrier frequency was higher in Asian (1 in 191 [95% CI, 1 in 142–258]) compared with White (1 in 417 [95% CI, 1 in 326–533]; P <0.001) or Black groups (1 in 508 [95% CI, 1 in 284–910]; P =0.004). The most common variants differed between populations. Of all variants, at least 25.0% were predicted as null variants. CONCLUSIONS: P/LP variants in LDLR are common. Expanding the use of reproductive carrier screening to include genes associated with FH presents another opportunity to identify people predisposed to cardiovascular disease.

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Section: Discussionmentioning

confidence: 83%

Section: Discussionmentioning

confidence: 99%

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Reproductive Carrier Screening: Identifying Families at Risk for Familial Hypercholesterolemia in the United States

Souter,

Becraft,

Brummitt

et al. 2024

Circ: Genomic and Precision Medicine

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“…As genetic health screening is offered to those who do not meet the NCCN genetic testing guidelines, only variants that are deemed pathogenic or likely pathogenic are identified by the testing lab and returned to the participants (see Methods). The full list of genes screened is shown in Table 1 and additional information on genetic health screening has recently been published [ 21 ]. HOP was designed to utilize direct participant engagement strategies, including direct mail, earned media, direct engagement, and social media.…”

Section: Resultsmentioning

confidence: 99%

“…DNA samples were sequenced at OHSU Knight Diagnostic Laboratories, a Clinical Laboratory Improvement Amendments lab at OHSU. Processes for genetic screening were covered in O'Brien et al [21] According to the IRB-approved protocol, only pathogenic and likely pathogenic variants for which National Comprehensive Cancer Network (NCCN) guidelines exist are returned to the participants. All other participants received a negative report explaining that no variants that affected their care were detected.…”

Section: Genes Screened and Reportingmentioning

confidence: 99%

Novel recruitment approaches and operational results for a statewide population Cohort for cancer research: The Healthy Oregon Project

Zhang,

Shafer,

Johnson-Camacho

et al. 2024

J. Clin. Trans. Sci.

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Background: Cancer health research relies on large-scale cohorts to derive generalizable results for different populations. While traditional epidemiological cohorts often use costly random sampling or self-motivated, preselected groups, a shift toward health system-based cohorts has emerged. However, such cohorts depend on participants remaining within a single system. Recent consumer engagement models using smartphone-based communication, driving projects, and social media have begun to upend these paradigms. Methods: We initiated the Healthy Oregon Project (HOP) to support basic and clinical cancer research. HOP study employs a novel, cost-effective remote recruitment approach to effectively establish a large-scale cohort for population-based studies. The recruitment leverages the unique email account, the HOP website, and social media platforms to direct smartphone users to the study app, which facilitates saliva sample collection and survey administration. Monthly newsletters further facilitate engagement and outreach to broader communities. Results: By the end of 2022, the HOP has enrolled approximately 35,000 participants aged 18-100 years (median = 44.2 years), comprising more than 1% of the Oregon adult population. Among those who have app access, ~87% provided consent to genetic screening. The HOP monthly email newsletters have an average open rate of 38%. Efforts continue to be made to improve survey response rates. Conclusion: This study underscores the efficacy of remote recruitment approaches in establishing large-scale cohorts for population-based cancer studies. The implementation of the study facilitates the collection of extensive survey and biological data into a repository that can be broadly shared and supports collaborative clinical and translational research.

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Using implementation science to evaluate a population-wide genomic screening program: Findings from the first 20,000 In Our DNA SC participants

Allen,

Hunt,

McMahon

et al. 2024

The American Journal of Human Genetics

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Population screening shows risk of inherited cancer and familial hypercholesterolemia in Oregon

Cited by 7 publications

References 48 publications

Reproductive Carrier Screening: Identifying Families at Risk for Familial Hypercholesterolemia in the United States

Reproductive Carrier Screening: Identifying Families at Risk for Familial Hypercholesterolemia in the United States

Novel recruitment approaches and operational results for a statewide population Cohort for cancer research: The Healthy Oregon Project

Using implementation science to evaluate a population-wide genomic screening program: Findings from the first 20,000 In Our DNA SC participants

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