Race, genetics and ancestry in medicine

One’s race and ethnicity are dynamic forces.
Race and ethnicity are shaped by geographic, cultural, and sociopolitical forces.
Race and ethnicity influence socioeconomic positioning  and lead to high morbidity and mortality for racial and ethnic minorities by allowing  inequitable access to resources, including health care.
Race and ethnicity  capture important epidemiologic information, including social determinants of health such as racism and discrimination, socioeconomic position, and environmental exposures.
Eliminating the use of race/ethnicity, information could enable inequitable health care systems to persist and exacerbate racial/ethnic inequities in health outcomes.
After analysts control for socioeconomic indicators such as education and income, environmental exposures, and other risk factors, there is a greater risk of adverse health outcomes among Black Americans than among White Americans.
Race is  associated with genetic ancestry and therefore indirectly related to genetic variants that may affect disease and health outcomes.
Genotyping methods and computational algorithms allow inference of geographic origins of a person’s ancestors:  differences in the cumulative frequency of thousands of genetic variants.
Race and ethnicity are self-ascribed or socially ascribed identities.
Race and ethnicity are often assigned  on the basis of physical characteristics.
Genetic ancestry is the genetic origin of one’s population.
Race/ethnicity may capture information about the presence of certain genetic variants, however, ancestry is a better predictor.
Genetic exchange among peoples from different ancestries in many populations and may correlate with individuals’ risk for certain genetic diseases.
There is substantial variation in ancestry among and within populations: U.S. Black populations, for example, have larger proportions of African than of European ancestry, which vary with the year and location in which samples are obtained.
Latino Americans, are an admixed group of European, Native American, and African ancestries.
The race/ethnicity categories used in research and clinical practice  are less precise than ancestry.
Unlike race, ancestry is a fixed characteristic of the genome.
Ancestry testing using millions of genetic markers has advanced understanding of globally and geographically diverse populations, leading to improved clinical predictions.
The proportion of African ancestry predicts differences in creatinine levels and estimated glomerular filtration rate (eGFR).
GFR varies within racial/ethnic groups.
The true cause of observed racial differences in creatinine levels is unknown.
Racial/ethnic differences in risk for disease and response to treatments are partially related to biologic factors, including genetic and epigenetic variants.
Ancestry helps to explain a portion of the biologic variation between and within groups.
In the first large-scale epigenetic study of asthma in minority children, ancestry explained 75% of the total variance in epigenetic patterns, suggesting that race/ethnicity, as a proxy for socioenvironmental exposures, explained the remaining 25%.
Race/ethnicity may be better than ancestry as a predictor of nongenetic factors.
Population-specific genetic variants contribute to clinical differences between racial/ethnic groups have been identified using a limited number of racially/ethnically diverse studies.
Genetic variants at the 6q25 locus identified in Latina women are associated with protection against breast cancer and originate from Indigenous American populations.
APOL1 genotypes, which are more common among people with West African ancestry, are strongly associated with focal sclerosing glomerulosclerosis, nondiabetic kidney disease, and HIV nephropathy, which can lead to early-onset end-stage kidney failure.
Prostate cancer is more than twice as common among Black men as among White men.
Variants at 8q24 that are associated with prostate-cancer risk in many populations, including variants that are more common in Black men and account for much of their excess risk of prostate cancer.
Among people with no response to clopidogrel, as many as 75% of Asians and Pacific Islanders lack the CYP2C19 genetic polymorphism required to metabolize the prodrug into its active form.
Although genetic variants underlying racial/ethnic differences in disease occurrence or outcomes exist, more often the causes of such differences are unknown, either because unrecognized nongenetic factors are key or because genetic research has failed to incorporate racial/ethnic diversity.
Globally genetic variation and genome architecture vary among populations.
More than 80% of participants in existing genomewide association studies are of European background.
Black and Latino people, who account for more than 30% of the U.S. population, represent  about 2% and <0.5%, respectively, who undergo genomic studies.
Less than 4.5% of federally funded pulmonary research has included minority populations.
The frequency and effect sizes of genetic variants associated with disease risk vary across populations.
Polygenic risk scores of populations with European ancestry have less predictive power when applied to non-European populations.
The polygenic risk score for breast cancer is about one third as predictive for Black women as for women of European descent.
It has been claimed that race adjustment may overestimate the GFR in some Black patients and contribute to delays in referral for renal transplantation, but the nonadjusted equation may underestimate Black patients’ GFR, resulting in underdosage or denial of certain medications or decreased  opportunities for kidney donation.
There is  lower average measures of normal lung function observed in non-White groups.
This could lead to underestimating the severity of lung disease, with clinical implications including delayed detection, missed opportunities for medical management of symptoms, denial of disability claims, and delayed access to lifesaving treatments such as lung transplantation.
On the flip side, using an equation derived from White populations in other racial/ethnic groups may lead to overdiagnosis, excessive follow-up testing, anxiety for patients, and compromised eligibility for treatments such as stem-cell transplantation for cancer.
The application of White-derived lung- and kidney-function equations to Black patients ignores long-recognized racial/ethnic differences in normal physiological function or biomarkers and is itself a form of racial discrimination.
The use of race/ethnicity may be important in measuring and addressing nongenetic causes of health inequities: Although the higher incidence of prostate cancer among Black men may be partially explained by genetic variants, but ancestry may be less important than race/ethnicity in determining clinical outcomes: among men with prostate cancer, race/ethnicity is associated with disparities in access and treatment.
Access to organ transplantation is systematically lower for Black patients with end-stage renal disease than for their White counterparts.
Attention to race/ethnicity bias is important for documenting disparities.
Interventions designed to reduce disparities have been demonstrated to improve outcomes.


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