scholarly journals Population structure and pharmacogenomic risk stratification in the United States

2020 ◽  
Author(s):  
Shashwat Deepali Nagar ◽  
Andrew B. Conley ◽  
I. King Jordan

AbstractPharmacogenomic (PGx) variants mediate how individuals respond to medication, and response differences among racial/ethnic groups have been attributed to patterns of PGx diversity. We hypothesized that genetic ancestry (GA) would provide higher resolution for stratifying PGx risk, since it serves as a more reliable surrogate for genetic diversity than self-identified race/ethnicity (SIRE), which includes a substantial social component. We analyzed a cohort of 8,628 individuals from the United States (US), for whom we had both SIRE information and whole genome genotypes, with a focus on the three largest SIRE groups in the US: White, Black, and Hispanic. Whole genome genotypes were used to characterize individuals’ continental ancestry fractions – European, African, and Native American – and individuals were grouped according to their GA profiles. SIRE and GA groups were found to be highly concordant. Continental ancestry predicts individuals’ SIRE with >96% accuracy, and accordingly GA provides only a marginal increase in resolution for PGx risk stratification. PGx variants are highly diverged compared to the genomic background; 82 variants show significant frequency differences among SIRE groups, and genome-wide patterns of PGx variation are almost entirely concordant with SIRE. Nevertheless, 97% of PGx variation is found within rather than between groups. Examples of highly differentiated PGx variants illustrate how SIRE partitions PGx variation based on group-specific ancestry patterns and contains valuable information for risk stratification. Finally, we show that individuals who identify as Black or Hispanic benefit more when SIRE is considered for treatment decisions than individuals from the majority White population.

BMC Biology ◽  
2020 ◽  
Vol 18 (1) ◽  
Author(s):  
Shashwat Deepali Nagar ◽  
Andrew B. Conley ◽  
I. King Jordan

Abstract Background Pharmacogenomic (PGx) variants mediate how individuals respond to medication, and response differences among racial/ethnic groups have been attributed to patterns of PGx diversity. We hypothesized that genetic ancestry (GA) would provide higher resolution for stratifying PGx risk, since it serves as a more reliable surrogate for genetic diversity than self-identified race/ethnicity (SIRE), which includes a substantial social component. We analyzed a cohort of 8628 individuals from the United States (US), for whom we had both SIRE information and whole genome genotypes, with a focus on the three largest SIRE groups in the US: White, Black (African-American), and Hispanic (Latino). Our approach to the question of PGx risk stratification entailed the integration of two distinct methodologies: population genetics and evidence-based medicine. This integrated approach allowed us to consider the clinical implications for the observed patterns of PGx variation found within and between population groups. Results Whole genome genotypes were used to characterize individuals’ continental ancestry fractions—European, African, and Native American—and individuals were grouped according to their GA profiles. SIRE and GA groups were found to be highly concordant. Continental ancestry predicts individuals’ SIRE with > 96% accuracy, and accordingly, GA provides only a marginal increase in resolution for PGx risk stratification. In light of the concordance between SIRE and GA, taken together with the fact that information on SIRE is readily available to clinicians, we evaluated PGx variation between SIRE groups to explore the potential clinical utility of race and ethnicity. PGx variants are highly diverged compared to the genomic background; 82 variants show significant frequency differences among SIRE groups, and genome-wide patterns of PGx variation are almost entirely concordant with SIRE. The vast majority of PGx variation is found within rather than between groups, a well-established fact for almost all genetic variants, which is often taken to argue against the clinical utility of population stratification. Nevertheless, analysis of highly differentiated PGx variants illustrates how SIRE partitions PGx variation based on groups’ characteristic ancestry patterns. These cases underscore the extent to which SIRE carries clinically valuable information for stratifying PGx risk among populations, albeit with less utility for predicting individual-level PGx alleles (genotypes), supporting the concept of population pharmacogenomics. Conclusions Perhaps most interestingly, we show that individuals who identify as Black or Hispanic stand to gain far more from the consideration of race/ethnicity in treatment decisions than individuals from the majority White population.


2021 ◽  
Author(s):  
Elizabeth Wrigley-Field ◽  
Kaitlyn M. Berry ◽  
Govind Persad

We provide the first age-standardized race/ethnicity-specific, state-specific vaccination rates for the United States, encompassing all states reporting race/ethnicity-specific vaccinations. The data reflect vaccinations through mid-October 2021. We use indirect age standardization to compare racial/ethnic state vaccination rates to national age-specific vaccination patterns. Results show that white and Black state median vaccination rates are, respectively, 89% and 76% of what would be predicted based on age; Hispanic and Native rates are almost identical to what would be predicted; and Asian-American/Pacific Islander rates are 110% of what would be predicted. We also find that racial/ethnic group vaccination rates are associated with state politics, as proxied by 2020 Trump vote share: for each percentage point increase in 2020 Trump vote share, vaccination rates decline by 1.08 percent of what would be predicted based on age. This decline is sharpest for Native American populations, although Native vaccinations are reported for relatively few states.


Author(s):  
Jay J. Xu ◽  
Jarvis T. Chen ◽  
Thomas R. Belin ◽  
Ronald S. Brookmeyer ◽  
Marc A. Suchard ◽  
...  

The coronavirus disease 2019 (COVID-19) epidemic in the United States has disproportionately impacted communities of color across the country. Focusing on COVID-19-attributable mortality, we expand upon a national comparative analysis of years of potential life lost (YPLL) attributable to COVID-19 by race/ethnicity (Bassett et al., 2020), estimating percentages of total YPLL for non-Hispanic Whites, non-Hispanic Blacks, Hispanics, non-Hispanic Asians, and non-Hispanic American Indian or Alaska Natives, contrasting them with their respective percent population shares, as well as age-adjusted YPLL rate ratios—anchoring comparisons to non-Hispanic Whites—in each of 45 states and the District of Columbia using data from the National Center for Health Statistics as of 30 December 2020. Using a novel Monte Carlo simulation procedure to perform estimation, our results reveal substantial racial/ethnic disparities in COVID-19-attributable YPLL across states, with a prevailing pattern of non-Hispanic Blacks and Hispanics experiencing disproportionately high and non-Hispanic Whites experiencing disproportionately low COVID-19-attributable YPLL. Furthermore, estimated disparities are generally more pronounced when measuring mortality in terms of YPLL compared to death counts, reflecting the greater intensity of the disparities at younger ages. We also find substantial state-to-state variability in the magnitudes of the estimated racial/ethnic disparities, suggesting that they are driven in large part by social determinants of health whose degree of association with race/ethnicity varies by state.


2019 ◽  
Vol 8 (2) ◽  
pp. 89-100 ◽  
Author(s):  
Gopal K Singh ◽  
Isaac E. Kim, Jr. ◽  
Mehrete Girmay ◽  
Chrisp Perry ◽  
Gem P. Daus ◽  
...  

Objectives: Dramatic increases in opioid and drug overdose mortality have occurred in the United States (US) over the past two decades. To address this national public health crisis and identify gaps in the literature, we analyzed recent empirical trends in US drug overdose mortality by key social determinants and conducted a selective review of the recent literature on the magnitude of the opioid crisis facing different racial/ethnic, socioeconomic, and rural-urban segments of the US population. Methods: We used the 1999-2017 mortality data from the US National Vital Statistics System to analyze trends in drug overdose mortality by race/ethnicity, age, and geographic area. Log-linear regression was used to model mortality trends. Using various key words and their combinations, we searched PubMed and Google Scholar for select peerreviewed journal articles and government reports published on the opioid epidemic between 2010 and 2018. Results: Our original analysis and review indicate marked increases in drug overdose mortality overall and by race/ethnicity and geographic regions, with adolescents and young adults experiencing steep increases in mortality between 1999 and 2017. Our selective search yielded 405 articles, of which 39 publications were selected for detailed review. Suicide mortality from drug overdose among teens aged 12-19 increased consistently between 2009 and 2017, particularly among teen girls. The rise of efficient global supply chains has increased opioid prescription use and undoubtedly contributed to the opioid epidemic. Many other important contributing factors to the epidemic include lack of education and economic opportunities, poor working conditions, and low social capital in disadvantaged communities. Conclusions and Global Health Implications: Our analysis and review indicate substantial disparities in drug overdoses and related mortality, pain management, and treatment outcomes according to social determinants. Increases in drug overdoses and resultant mortality are not only unique to the US, but have also been observed in other industrialized countries. Healthcare systems, community leaders, and policymakers addressing the opioidepidemic should focus on upstream structural factors including education, economic opportunity, social cohesion, racial/ethnic disadvantage, geographic isolation, and life satisfaction. Key words: • Opioids • Drug overdose • Mortality • Pain management • Treatment • Race/Ethnicity • Social determinants • Health disparities Copyright © 2019 Singh et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


Author(s):  
Dawn Langan Teele

This chapter presents a case study of women's enfranchisement in the United States. It argues that the formation of a broad coalition of women, symbolized by growing membership in a large non-partisan suffrage organization, in combination with competitive conditions in state legislatures, was crucial to securing politicians' support for women's suffrage in the states. The chapter first gives a broad overview of the phases of the US suffrage movement, arguing that the salience of political cleavages related to race, ethnicity, nativity, and class influenced the type of movement suffragists sought to build. It then describes the political geography of the Gilded Age, showing how the diversity of political competition and party organization that characterized the several regions mirrors the pattern of women's enfranchisement across the states.


Author(s):  
Matthew D. Moore ◽  
Anne E. Brisendine ◽  
Martha S. Wingate

Objective This study was aimed to examine differences in infant mortality outcomes across maternal age subgroups less than 20 years in the United States with a specific focus on racial and ethnic disparities. Study Design Using National Center for Health Statistics cohort-linked live birth–infant death files (2009-2013) in this cross-sectional study, we calculated descriptive statistics by age (<15, 15–17, and 18–19 years) and racial/ethnic subgroups (non-Hispanic white [NHW], non-Hispanic black [NHB], and Hispanic) for infant, neonatal, and postneonatal mortality. Adjusted odds ratios (aOR) were calculated by race/ethnicity and age. Preterm birth and other maternal characteristics were included as covariates. Results Disparities were greatest for mothers <15 and NHB mothers. The risk of infant mortality among mothers <15 years compared to 18 to 19 years was higher regardless of race/ethnicity (NHW: aOR = 1.40, 95% confidence interval [CI]: 1.06–1.85; NHB: aOR = 1.28, 95% CI: 1.04–1.56; Hispanic: aOR = 1.36, 95%CI: 1.07–1.74). Compared to NHW mothers, NHB mothers had a consistently higher risk of infant mortality (15–17 years: aOR = 1.12, 95% CI: 1.03–1.21; 18–19 years: aOR = 1.21, 95% CI: 1.15–1.27), while Hispanic mothers had a consistently lower risk (15–17 years: aOR = 0.72, 95% CI: 0.66–0.78; 18–19 years: aOR = 0.74, 95% CI: 0.70–0.78). Adjusting for preterm birth had a greater influence than maternal characteristics on observed group differences in mortality. For neonatal and postneonatal mortality, patterns of disparities based on age and race/ethnicity differed from those of overall infant mortality. Conclusion Although infants born to younger mothers were at increased risk of mortality, variations by race/ethnicity and timing of death existed. When adjusted for preterm birth, differences in risk across age subgroups declined and, for some racial/ethnic groups, disappeared. Key Points


2020 ◽  
Vol 4 (5) ◽  
Author(s):  
Jingxuan Zhao ◽  
Kimberly D Miller ◽  
Farhad Islami ◽  
Zhiyuan Zheng ◽  
Xuesong Han ◽  
...  

Abstract Background Little is known about disparities in economic burden due to premature cancer deaths by race or ethnicity in the United States. This study aimed to compare person-years of life lost (PYLLs) and lost earnings due to premature cancer deaths by race/ethnicity. Methods PYLLs were calculated using recent national cancer death and life expectancy data. PYLLs were combined with annual median earnings to generate lost earnings. We compared PYLLs and lost earnings among individuals who died at age 16-84 years due to cancer by racial/ethnic groups (non-Hispanic [NH] White, NH Black, NH Asian or Pacific Islander, and Hispanic). Results In 2015, PYLLs due to all premature cancer deaths were 6 512 810 for NH Whites, 1 196 709 for NH Blacks, 279 721 for NH Asian or Pacific Islanders, and 665 968 for Hispanics, translating to age-standardized lost earning rates (per 100 000 person-years) of $34.9 million, $43.5 million, $22.2 million, and $24.5 million, respectively. NH Blacks had higher age-standardized PYLL and lost earning rates than NH Whites for 13 of 19 selected cancer sites. If age-specific PYLL and lost earning rates for NH Blacks were the same as those of NH Whites, 241 334 PYLLs and $3.2 billion lost earnings (22.6% of the total lost earnings among NH Blacks) would have been avoided. Disparities were also observed for average PYLLs and lost earnings per cancer death for all cancers combined and 18 of 19 cancer sites. Conclusions Improving equal access to effective cancer prevention, screening, and treatment will be important in reducing the disproportional economic burden associated with racial/ethnic disparities.


2020 ◽  
Vol 6 ◽  
pp. 233372142092041 ◽  
Author(s):  
M. Courtney Hughes ◽  
Erin Vernon

Background: Racial/ethnic minority populations in the United States are less likely to utilize hospice services nearing their end of life, potentially diminishing their quality of care while also increasing medical costs. Objective: Explore the minority hospice utilization gap from the hospice perspective by examining perceived barriers and facilitators as well as practices and policies. Method: Qualitative surveys were conducted with 41 hospices across the United States. Qualitative data analysis included performing a limited content analysis, including the identification of themes and representative quotations. Results: Commonly reported barriers to hospice care for racial/ethnic minorities included culture/beliefs, mistrust of the medical system, and language barriers. A major theme pertaining to successful minority hospice enrollment was an inclusive culture that provided language services, staff cultural training, and a diverse staff. Another major theme was the importance of community outreach activities that extended beyond the medical community and forming relationships with churches, racial/ethnic minority community leaders, and Native American reservations. Conclusion: The importance of incorporating a culture of inclusivity by forming committees, providing language services, and offering culturally competent care emerged in this qualitative study. Building strong external relationships with community groups such as churches is a strategy used to increase racial/ethnic minority utilization of hospice.


2020 ◽  
Vol 135 (1_suppl) ◽  
pp. 149S-157S
Author(s):  
Benedict I. Truman ◽  
Ramal Moonesinghe ◽  
Yolanda T. Brown ◽  
Man-Huei Chang ◽  
Jonathan H. Mermin ◽  
...  

Objective Federal funds have been spent to reduce the disproportionate effects of HIV/AIDS on racial/ethnic minority groups in the United States. We investigated the association between federal domestic HIV funding and age-adjusted HIV death rates by race/ethnicity in the United States during 1999-2017. Methods We analyzed HIV funding data from the Kaiser Family Foundation by federal fiscal year (FFY) and US age-adjusted death rates (AADRs) by race/ethnicity (Hispanic, non-Hispanic white, non-Hispanic black, and Asian/Pacific Islander and American Indian/Alaska Native [API+AI/AN]) from Centers for Disease Control and Prevention WONDER detailed mortality files. We fit joinpoint regression models to estimate the annual percentage change (APC), average APC, and changes in AADRs per billion US dollars in HIV funding, with 95% confidence intervals (CIs). For 19 data points, the number of joinpoints ranged from 0 to 4 on the basis of rules set by the program or by the user. A Monte Carlo permutation test indicated significant ( P < .05) changes at joinpoints, and 2-sided t tests indicated significant APCs in AADRs. Results Domestic HIV funding increased from $10.7 billion in FFY 1999 to $26.3 billion in FFY 2017, but AADRs decreased at different rates for each racial/ethnic group. The average rate of change in AADR per US billion dollars was −9.4% (95% CI, −10.9% to −7.8%) for Hispanic residents, −7.8% (95% CI, −9.0% to −6.6%) for non-Hispanic black residents, −6.7% (95% CI, −9.3% to −4.0%) for non-Hispanic white residents, and −5.2% (95% CI, −7.8% to −2.5%) for non-Hispanic API+AI/AN residents. Conclusions Increased domestic HIV funding was associated with faster decreases in age-adjusted HIV death rates for Hispanic and non-Hispanic black residents than for residents in other racial/ethnic groups. Increasing US HIV funding could be associated with decreasing future racial/ethnic disparities in the rate of HIV-related deaths.


Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 3069-3069
Author(s):  
Casey L O'Connell ◽  
Pedram Razavi ◽  
Roberta McKean-Cowdin ◽  
Malcolm C. Pike

Abstract Abstract 3069 Poster Board III-6 Background Acute lymphoblastic leukemia (ALL) is an aggressive malignancy whose incidence declines through adolescence and then increases steadily with age. Prognosis appears to be inversely related to age among adults. We sought to explore the impact of race/ethnicity on incidence and survival among adults with ALL in the United States (US). Methods We examined trends in incidence and survival among adults with ALL in the US using the National Cancer Institute's Surveillance, Epidemiology and End Results (SEER) program which includes data from 17 SEER registries. We calculated the incidence rates for the most recent time period (2001-2005) because the classification for ALL subtypes was more complete during this time. For the survival analysis we used the data collected between 1975 and 2005. We categorized race/ethnicity into 5 mutually exclusive categories: non-Hispanic whites (NHW), Hispanic whites (HW), African Americans (AA), Asian/Pacific Islanders (API) and American Indians/Native Alaskans (AI/NA). Hispanic ethnicity was defined using SEER's Hispanic-origin variable which is based on the NAACCR Hispanic Identification Algorithm (NHIA); 11 patients dually coded as black and Hispanic were included in the AA group for our analyses. Few ALL cases were identified among AI/NA, so that group is not represented in the final analyses. We included ALL cases coded in the SEER registry using the International Classification of Disease for Oncology (ICD-0-3) as 9827-9829 and 9835-9837. We excluded cases of Burkitt's leukemia (n=228), cases that were not confirmed by microscopic or cytologic tests (n=132), cases that were reported only based on autopsy data (n=3) and cases whose race/ethnicity were unknown (n=20). The average annual incidence rates per 100,000 for 2001-2005, age-adjusted to the 2000 US standard population were calculated using SEER*Stat Version 6.4.4 statistical software. We used multivariate Cox hazard models stratified by SEER registry and age category to estimate the hazard ratios (HR) and 95% confidence intervals (95% CI) for relative survival of adult ALL cases across race/ethnicity, sex and cell of origin (B- or T-cell). All models were adjusted for the diagnosis era, and use of non-CNS radiation. The model also included an interaction term for age and diagnosis era. We performed a separate stratified analysis of the impact of race/ethnicity on survival within age subgroups (20-29, 30-39, 40-59, 60-69, 70+). Results The highest incidence rate (IR) of ALL was observed for HW (IR: 1.60; 95% CI: 1.43-1.79). HW had a significantly higher IR across all age categories as compared to the other racial/ethnic groups, while AA had the lowest IR. In particular, the observed rate of B-cell ALL among HW (IR 0.77; 95% CI 0.69-0.87) was more than twice that of NHW (IR: 0.29; 95% CI: 0.27-0.32) and more than three times the rate observed among AA (IR: 0.20; 95% CI: 0.15-0.26). In contrast, we did not observe statistically significant variability in the rates of T-cell ALL across race/ethnic groups (overall IR: 0.12; 95% CI: 0.11-0.14). Survival was significantly poorer among AA (HR: 1.26; 95% CI: 1.09-1.46), HW (HR: 1.21; 95% CI: 1.09-1.46), and API (HR: 1.18; 95% CI: 1.06-1.32) compared to NHW with all subtypes of ALL. Among adults younger than 40 with B-cell ALL, survival was significantly poorer among AA (HR: 1.60; 95% CI:1.021-2.429) and HW (HR: 1.53; 95% CI:1.204-1.943) with a non-signficant trend among API (HR: 1.22; 95% 0.834-1.755) compared to NHW. Survival differences between the different racial/ethnic groups were no longer statistically significant among adults with B-cell ALL over the age of 40. For T-cell ALL, survival was significantly poorer among AA (HR: 1.61; 95% CI: 1.22-2.10), HW (HR: 1.49; 95% CI: 1.14-1.93) and API (HR: 1.57; 95% CI: 1.13-2.13), as compared to NHW. A similar survival pattern by age (adults above and below age 40 years) was observed for T-cell as described for B-cell, with AA under 40 having a particularly dismal prognosis (HR: 2.89; 95% CI 1.96-4.17) compared to NHW. Conclusions The incidence rate of B-cell ALL among adults in the US is higher among HW than other ethnic groups. Survival is significantly poorer among AA and HW than among NHW under the age of 40 with B-cell ALL. Survival is also significantly poorer among AA, HW and API than among NHW with T-cell ALL in adults under 40. Survival trends appear to converge after the age of 40 among all racial/ethnic groups. Disclosures No relevant conflicts of interest to declare.


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