Genetic Ancestry and Self-reported Ethnicity in Carrier Screening
Ontology highlight
ABSTRACT: Current professional society guidelines recommend genetic carrier screening be offered on the basis of ethnicity, or when using expanded carrier screening panels, they recommend to compute residual risk based on ethnicity. We investigated the reliability of self-reported ethnicity in 9125 subjects referred to carrier screening. We identified several discrepancies between the two sources of self-reported ethnicity and genetic ancestry. As a result, carrier rates and residual risks provided for patient decision-making are impacted if using self-reported ethnicity. We recommend the routine use of pan-ethnic carrier screening panels in reproductive medicine. Furthermore, the use of an ancestry model would allow better estimation of carrier rates and residual risks.
SECONDARY ACCESSION(S): PRJNA417535PRJNA417534
REPOSITORIES: dbGaP
Similar Datasets
Project description:Evaluating Genetic Ancestry and Self-Reported Ethnicity in the Context of Carrier Screening
| PRJNA417534 | ENA
Project description:Evaluating Genetic Ancestry and Self-Reported Ethnicity in the Context of Carrier Screening
| PRJNA417535 | ENA
Project description:(1) In clinical practice and biomedical research populations are often divided categorically into distinct racial and ethnic groups. In reality, these categories comprise diverse groups with highly heterogeneous histories, cultures, traditions, religions, as well as social and environmental exposures. While the factors captured by these categories contribute to clinical practice and biomedical research, the use of race/ethnicity is widely debated. As a response to this debate, genetic ancestry has been suggested as a complement or alternative to this categorization. However, few studies have examined the effect of genetic ancestry, racial/ethnic identity, and environmental exposures on biological processes. Herein, we examine the contribution of self-identification within ethnicity, genetic ancestry, and environmental exposures on epigenetic modification of DNA methylation, a phenomenon affected by both genetic and environmental factors. We typed over 450,000 variably methylated CpG sites in primary whole blood of 573 individuals of Mexican and Puerto Rican descent who also had high-density genotype data. We found that methylation levels at a large number of CpG sites were significantly associated with ethnicity even when adjusting for genetic ancestry. In addition, we found an enrichment of ethnicity-associated sites amongst loci previously associated with environmental and social exposures. Interestingly, one of the strongest associated sites is driven by the Duffy Null blood type variant, demonstrating a new function of the locus in lymphocytes. Overall, the methylation changes associated with race/ethnicity, driven by both genes and environment, highlight the importance of measuring and accounting for both self-identified race/ethnicity and genetic ancestry in clinical and biomedical studies and the benefits of studying diverse populations. (2) In epigenome-wide association studies (EWAS), different methylation profiles of distinct cell-types may lead to false discoveries. We introduce ReFACTor, a method based on principal component analysis (PCA) for the correction of cell-type heterogeneity in EWAS. ReFACTor does not require knowledge of the cell counts, and it obtains improved estimates of the cell-type composition, resulting in improved power and control for false positives in EWAS.
2016-02-29 | GSE77716 | GEO
Project description:(1) In clinical practice and biomedical research populations are often divided categorically into distinct racial and ethnic groups. In reality, these categories comprise diverse groups with highly heterogeneous histories, cultures, traditions, religions, as well as social and environmental exposures. While the factors captured by these categories contribute to clinical practice and biomedical research, the use of race/ethnicity is widely debated. As a response to this debate, genetic ancestry has been suggested as a complement or alternative to this categorization. However, few studies have examined the effect of genetic ancestry, racial/ethnic identity, and environmental exposures on biological processes. Herein, we examine the contribution of self-identification within ethnicity, genetic ancestry, and environmental exposures on epigenetic modification of DNA methylation, a phenomenon affected by both genetic and environmental factors. We typed over 450,000 variably methylated CpG sites in primary whole blood of 573 individuals of Mexican and Puerto Rican descent who also had high-density genotype data. We found that methylation levels at a large number of CpG sites were significantly associated with ethnicity even when adjusting for genetic ancestry. In addition, we found an enrichment of ethnicity-associated sites amongst loci previously associated with environmental and social exposures. Interestingly, one of the strongest associated sites is driven by the Duffy Null blood type variant, demonstrating a new function of the locus in lymphocytes. Overall, the methylation changes associated with race/ethnicity, driven by both genes and environment, highlight the importance of measuring and accounting for both self-identified race/ethnicity and genetic ancestry in clinical and biomedical studies and the benefits of studying diverse populations. (2) In epigenome-wide association studies (EWAS), different methylation profiles of distinct cell-types may lead to false discoveries. We introduce ReFACTor, a method based on principal component analysis (PCA) for the correction of cell-type heterogeneity in EWAS. ReFACTor does not require knowledge of the cell counts, and it obtains improved estimates of the cell-type composition, resulting in improved power and control for false positives in EWAS. Bisulphite converted DNA from 573 samples were hybridised to the Illumina Infinium 450k Human Methylation Beadchip and a complete blood count with automated white blood cell differential was performed by automated flow cytometry for 95 of the samples.
2016-02-29 | E-GEOD-77716 | biostudies-arrayexpress
Project description:The influence of genetics on DNA methylation (DNAme) variation is well documented, yet confounding from population stratification is often unaccounted for in DNAme association studies. Existing approaches have been developed to address confounding by population stratification by directly using DNAme data, but have not been validated in additional human populations or tissues, such as the placenta. Results: To aid future placental DNAme studies in assessing population stratification, we developed an ethnicity classifier, PLANET (placental elastic net DNAme ethnicity classifier), on combined Infinium Human Methylation 450k BeadChip array (HM450k) data from placental samples. We used data from five North American cohorts from private and public repositories (n = 509) and show that PLANET can not only accurately predict (accuracy = 0.9379, kappa = 0.8227) major classes of self-reported ethnicity/race (African: n = 58, Asian: n = 53, Caucasian: n = 389), but can also produce probabilities that are highly correlated with genetic ancestry inferred from genome-wide SNP (>2.5 million SNP) and ancestry informative markers (n=50) data. We found that PLANET’s ethnicity classification relies on 1860 DNAme microarray sites, and over half of these were also linked to nearby genetic polymorphisms (n=955). Lastly, we found our placental-optimized method outperforms existing approaches in assessing population stratification in our placental samples from individuals of Asian, African, and Caucasian ethnicities. Conclusion: PLANET outperforms existing methods and heavily relies on the genetic signal present in DNAme microarray data. PLANET can be used to address population stratification in future placental DNAme association studies, and will be especially useful when ethnicity information is missing and genotyping markers are unavailable.
2020-10-14 | GSE128827 | GEO
Project description:<p>The National Children's Study (NCS) is a multi-year prospective epidemiological study tasked with identifying a nationally representative sample of 100,000 children and following them from pregnancy through age 21 to study environmental impacts on growth, development, and health. Determination of NCS enrollee ancestry is important for assessing the diversity of study enrollees and for examining the effect of ancestry on various health outcomes. We estimated the genetic ancestry of a convenience sample of 641 parents enrolled at the 7 original NCS Vanguard sites by analyzing 29,972 markers on exome arrays, using the participants of the 1000 Genomes Project (1KG) super populations (e.g. European, East Asian) as reference populations, and compared this to self-reported ethnicity and race. Self-reported ethnicity and race agreed with predicted super population in 98.9% of individuals. NCS individuals identified as Asian by self-report had genetic ancestry of either South Asian or Asian groups, while those reporting as either Hispanic White or Hispanic Other had similar genetic ancestry. Of the 33 individuals who self-reported as Multiracial or Non-Hispanic Other, 11 (33%) matched the South Asian and Asian groups, while these groups were less represented in the other reported categories (27/609, 4.4%). Our data suggest that self-reported ethnicity and race categories have some limitations in accurately capturing this information for Hispanic and South Asian populations. Overall, our data indicate that despite the complexity of the U.S. population, individuals know their ancestral origins and that self-reported ethnicity and race is a reliable indicator of genetic ancestry.</p>
| phs000662 | dbGaP
Project description:Whole peripheral blood samples collected into Tempus tubes from 189 adult participants in the Center for Health Discovery and Well Being study of Emory University and Georgia Tech, in Midtown Atlanta. The sample is of mixed ethnicity, and is part of a survey of the impact of genetics and lifestyle on gene expression and clinical attributes. Sample annotations include gender, self-reported ethnicity, zipcode of current address, and percent body fat, as well as technical features of the study (Sentrix plate ID, date of hybridization, and RNA quality RIN score.
2013-03-01 | GSE35846 | GEO
Project description:Background: Differences in breast cancer outcomes according to race/ethnicity have been reported. Hispanic/Latino (H/L) populations are a genetically admixed and heterogeneous group, with variable fractions of European, Indigenous American and African ancestries. Some studies suggest that breast cancer-specific mortality is higher in U.S. Hispanic/Latinas compared to non-Hispanic Whites (NHW) even after adjustment for socioeconomic status and education. The molecular profile of breast cancer has been widely described in NHWs but equivalent knowledge is lacking in Hispanic/Latinas. We have previously reported that the most prevalent breast cancer intrinsic subtype in Colombian H/L women was Luminal B as defined by surrogate St. Gallen 2013 criteria. In this study we explored ancestry-associated differences in molecular profiles of Luminal B tumors among these highly admixed women. Methods: We performed whole-transcriptome RNA-seq analysis in 42 Luminal tumors (21 Luminal A and 21 Luminal B) from Colombian women. Genetic ancestry was estimated from a panel of 80 ancestry-informative markers (AIM). We categorized patients according to Luminal subtype and to the proportion of European and Indigenous American ancestry and performed differential expression analysis comparing Luminal B against Luminal A tumors according to the assigned ancestry groups. Results: We found 5 genes potentially modulated by genetic ancestry: ERBB2 (Fold Change = 2.367, padj < 0.01), GRB7 (Fold Change = 2.327, padj < 0.01), GSDMB (Fold Change = 1.723, padj < 0.01, MIEN1 (Fold Change = 2.195, padj < 0.01 and ONECUT2 (Fold Change = 2.204, padj < 0.01). In the replication set we found a statistical significant association between European ancestry fraction and the expression levels of ERBB2 (p = 0.02, B = 2.49) and ONECUT2 (p = 0.04, B = -4.87). We also observed statistical significant associations for ERBB2 expression with Indigenous American ancestry (p < 0.001, B = 3.82). This association was not biased by the distribution of HER2+ tumors among the groups analyzed. Conclusions: Our results suggest that genetic ancestry in Hispanic/Latina women might modify ERBB2 gene expression in Luminal tumors. Further analyses are needed to confirm these findings and explore their prognostic value.
2017-10-04 | GSE101927 | GEO
Project description:Tumor eQTM screening reveals distinct CpG panels for deconvolving cancer immune signatures
| PRJNA798830 | ENA