Genomics and Disparities in Health and Health Care ...
Transcript of Genomics and Disparities in Health and Health Care ...
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Genomics and Disparities in Health and Health Care:
Challenges and Opportunities
David R. Williams, PhD, MPH Florence & Laura Norman Professor of Public Health
Professor of African & African American Studies and of Sociology
Harvard University
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Pattern
There are Large Racial/Ethnic Disparities in Access to Health Care
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Percent of people under age 65 with any health insurance, 2006
83
65
85 88
63
0
10
20
30
40
50
60
70
80
90
100
Black Hispanic Asian &PI White American Indian
Year
% o
f peo
ple
unde
r ag
e 65
with
any
hea
lth
insu
ranc
e Black
Hispanic
Asian &PI
White
American Indian
National Healthcare Disparities Report 2008
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Percent of people under age 65 with any public insurance, 2006
47
60
27 24
63
0
10
20
30
40
50
60
70
80
Black Hispanic Asian &PI White American Indian
Year
% o
f peo
ple
unde
r ag
e 65
with
any
pu
blic
ins
uran
ce Black
Hispanic
Asian &PI
White
American Indian
National Healthcare Disparities Report 2008
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Percent of adults with unmet medical need in the last 12 months, 2005
21
18
27
13
0
5
10
15
20
25
30
Black Hispanic Asian &PI White
Year
% o
f pe
ople
with
unm
et m
edic
al n
eed
in th
e la
st 1
2 m
onth
s
Black
Hispanic
Asian &PI
White
National Healthcare Disparities Report 2008
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Pattern
There are Large Racial/Ethnic Disparities in the Quality and
Intensity of Health Care
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Race and Medical Care • Across virtually every therapeutic intervention,
ranging from high technology procedures to the most elementary forms of diagnostic and treatment interventions, minorities receive fewer procedures and poorer quality medical care than whites.
• These differences persist even after differences in health insurance, SES, stage and severity of disease, co-morbidity, and the type of medical facility are taken into account.
• They persist in contexts such as Medicare and the VA Health System, where differences in economic status and insurance coverage are minimized.
Institute of Medicine, 2002
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Ethnicity and Analgesia A chart review of 139 patients with isolated long-bone
fracture at UCLA Emergency Department (ED): • All patients aged 15 to 55 years, had the injury within 6
hours of ER visit, had no alcohol intoxication. • 55% of Hispanics received no analgesic compared to 26%
of non-Hispanic whites. • With simultaneous adjustment for sex, primary language,
insurance status, occupational injury, time of presentation, total time in ED, fracture reduction and hospital admission, Hispanic ethnicity was the strongest predictor of no analgesia.
• After adjustment for all factors, Hispanics were 7.5 times more likely than NH whites to receive no analgesia.
Todd, et al. 1993
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Disparities in the Clinical Encounter: The Core Paradox
How could well-meaning and highly educated
health professionals, working in their usual
circumstances with diverse populations of
patients, create a pattern of care that appears to
be discriminatory?
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Unconscious Discrimination • When one holds a negative stereotype about a
group and meets someone who fits the stereotype s/he will discriminate against that individual
• Stereotype-linked bias is an – Automatic process – Unconscious process
• It occurs even among persons who are not prejudiced
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“I am not racist: I know I don’t stereotype”
• Conclusive evidence that stereotypes are activated automatically (without intent). • Individuals frequently are not aware of activation nor impact on their perceptions, emotions and behavior. • They are activated more quickly and effortlessly than conscious cognition. • Many cognitive processes result in confirmation of expectancies (we process information in ways that support our beliefs). van Ryn, 2003
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Distinctive Social Exposures
Negatively Stereotyped
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Percent of Whites Agreeing that Blacks are
General Social Survey (Davis and Smith), 1990
0
10
20
30
40
50
60
70
Lazy Prefer Welfare Prone toViolence
Unintelligent
44
29
51 56
Perc
ent S
uppo
rt
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Stereotypes in Our Culture
Verhaeghen et al. British J Psychology, 2011
• BEAGLE (Bound Encoding of the Aggregate Language Environment) Project contains about 10 million words from a sample of books, newspapers, magazine articles, etc.
• A good representation of American culture • Equivalent to what the average college-level
student has read in her lifetime • Statistically analyzed the associative strength
between pairs of words • Provides estimate of how often Americans have
seen or heard words paired over their lifetime
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Stereotypes in Our Culture
Verhaeghen et al. British J Psychology, 2011
BLACK poor .64 BLACK violent .43 BLACK religious .42 BLACK lazy .40 BLACK cheerful .40 BLACK dangerous .33 FEMALE distant .37 FEMALE warm .35 FEMALE gentle .34 FEMALE passive .34
WHITE wealthy .48 WHITE progressive .41 WHITE conventional .37 WHITE stubborn .32 WHITE successful .30 WHITE educated .30 MALE dominant .46 MALE leader .31 MALE logical .31 MALE strong .31
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Unconscious Discrimination
Can be reduced under certain conditions
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18
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Implications • We need to ensure equitable access to genomic medicine
• The multiple barriers to accessing all of the benefits of genomics need to be effectively addressed
• Systematic efforts to build trust and partnerships with historically marginalized populations is important
• Public outreach programs can enhance understanding and awareness of genomics
• We need to strengthen the genomic education of healthcare providers
• We need to enhance science literacy at all education levels
Green et al. Nature, 2011
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Pattern
There are Large Racial Disparities In Health
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Race/Ethnicity and Health: Two Patterns • Racial groups with a long history characterized by
economic exploitation, social stigmatization, and geographic marginalization have markedly elevated levels of poor health outcomes:
-- Blacks or African Americans -- American Indians and Alaskan Natives -- Native Hawaiians and other Pacific Islanders • Immigrant groups tend to have better health than the
U.S. average, but their health tends to worsen over time and across subsequent generations:
-- Asians -- Hispanics
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Racial Disparities in Health
• African Americans have higher death rates than Whites for 12 of the 15 leading causes of death.
• Blacks and American Indians have higher age-specific death rates than Whites from birth through the retirement years.
• Hispanics have higher death rates than whites for diabetes, hypertension, liver cirrhosis & homicide
• Asians tend to have lower overall mortality rates than Whites
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Pattern
Racial Disparities In Health Are Persistent Over Time
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40
60
80
1950 1960 1970 1980 1990 2000 2006
Life
Exp
ecta
ncy
WhiteBlack
Life Expectancy Lags, 1950-2006
National Vital Statistics Report, 2009
63.6
70.6
60.8
69.1
74.4 76.1
69.1 68.2
71.7
64.1
71.4 73.2
78.2 77.6
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Diabetes Death Rates 1955-1998
12.610.4 8.6
11.7 11.9
17.0
24.4
46.4
52.8
24.3
0.0
10.0
20.0
30.0
40.0
50.0
60.0
1955 1975 1985 1995 1996-98Year
Dea
ths p
er 1
00,0
00 P
opul
atio
n
0.0
0.5
1.0
1.5
2.0
2.5
3.0
3.5
4.0
4.5
5.0
Am
Ind/
W R
atio
WhiteAm IndAm Ind/W Ratio
Source: Indian Health Service; Trends in Indian Health 2000-2001
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Pattern
Minorities get sick younger, have more severe illness and die sooner than Whites
Williams et al 2010, NYAS
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Early Onset: Heart Failure
A 20-year follow-up of young adults in the CARDIA study found that incident heart failure before the age of 50 was 20 times more common in Blacks than Whites, with the average age of onset being 39 years old
Bibbins-Domingo et al. 2009, NEJM;
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Allostatic Load 10 biomarkers High-risk thresholds * 1. Systolic blood pressure 127 mm HG 2. Diastolic blood pressure 80 mm HG 3. Body Mass Index 30.9 4. Glycated hemoglobin 5.4% 5. Albumin 4.2 g/dL 6. Creatinine clearance 66 mg/dL 7. Triglycerides 168 mg/dL 8. C-reactive protein 0.41 mg/dL 9. Homocysteine 9 μmol/L 10. Total cholesterol 225 * = < 25th percentile for creatinine clearance; >75th percentile for others Geronimus, et al., AJPH, 2006
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1.1
1.8
2.4
3.3
4
1.6
2.2
3.0
4.0
4.8
1
2
3
4
5
6
18-24 25-34 35-44 45-54 55-64
Mea
n
AGE
WhiteBlack
Geronimus, et al., AJPA, 2006
Mean Score on Allostatic Load by Age
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Making Sense of “Racial” Differences • Race reflects simultaneous unmeasured
confounding for genetic (ancestral history and geographic origins) factors and environmental exposures
• Race reflects unmeasured confounding due to the current social environment
• Race reflects unmeasured confounding due to exposures over the life course (and generations) and biological adaptation to these environmental exposures. This includes changes in gene expression
Williams et al. 2010 An NY Acad Sci; Cooper et al. 2003, N Eng J Med
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Central Role of Socioeconomic Status (SES)
Typically measured by income, education, or occupation, SES is one of the most robust
determinants of variations in health in virtually every society
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Relative Risk of Premature Death by Family Income (U.S.)
0.0
0.5
1.0
1.5
2.0
2.5
3.0
3.5
4.0
<10K 10-19K 20-29K 30-39K 40-49K 50-99K 100+K
Rel
ativ
e R
isk
Family Income in 1980 (adjusted to 1999 dollars)
9-year mortality data from the National Longitudinal Mortality Survey
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Pattern
Racial/Ethnic Disparities in Health reflect more than just SES
Minorities have elevated levels of illness even at comparable levels of SES
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Life Expectancy At Age 25
Murphy, NVSS 2000
Group White Black Difference
All
53.4 48.4 5.0
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Life Expectancy At Age 25
Murphy, NVSS 2000; Braveman et al. AJPH, 2010; NLMS 1988-1998
Group White Black Difference
All Education
53.4 48.4 5.0
a. 0-12 Years 50.1 b. 12 Years 54.1 c. Some College 55.2 d. College Grad 56.5 Difference 6.4
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Life Expectancy At Age 25
Murphy, NVSS 2000; Braveman et al. AJPH, 2010; NLMS 1988-1998
Group White Black Difference
All Education
53.4 48.4 5.0
a. 0-12 Years 50.1 47.0 b. 12 Years 54.1 49.9 c. Some College 55.2 50.9 d. College Grad 56.5 52.3 Difference 6.4 5.3
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Life Expectancy At Age 25
Murphy, NVSS 2000; Braveman et al. AJPH, 2010; NLMS 1988-1998
Group White Black Difference
All Education
53.4 48.4 5.0
a. 0-12 Years 50.1 47.0 3.1 b. 12 Years 54.1 49.9 4.2 c. Some College 55.2 50.9 4.3 d. College Grad 56.5 52.3 4.2 Difference 6.4 5.3
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Meharry vs Johns Hopkins A 1958 – 65, all Black, cohort of Meharry Medical
College MDs was compared with a 1957- 64, all White, cohort of Johns Hopkins MDs. 23-25 years later, the Black MDs were more likely to have: higher risk of CVD (RR=1.65) earlier onset of disease incidence rates of diabetes & hypertension that
were twice as high higher incidence of coronary artery disease (1.4
times) higher case fatality (52% vs 9%)
Thomas et al., 1997 J. Health Care for Poor and Underserved
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Why Race Still Matters
1. Health is affected not only by current SES but by exposure to social and economic adversity over the life course.
2. All indicators of SES are non-equivalent across race. Compared to whites, blacks & Hispanics receive less income at the same levels of education, have less wealth at the equivalent income levels, and have less purchasing power (at a given income level) because of higher costs of goods and services.
3. Personal experiences of discrimination and institutional racism are added pathogenic factors that can affect the health in multiple ways.
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Non Equivalence of SES across Race
Compared to whites, blacks and Hispanics: -- Receive less income at the same levels of
education, -- have less wealth at the equivalent income
levels, and -- have less purchasing power (at a given level
of income) because of higher costs of goods and services.
Williams & Collins, 1995; Ann Rev Soc
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Distinctive Social Exposures
Measurement Issue: The minority poor are poorer than the white poor
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Wealth of Whites and of Minorities per $1 of Whites, 2000
Household Income White B/W
Ratio Hisp/W Ratio
Total $ 79,400 9¢ 12¢
Poorest 20% $ 24,000 1¢ 2¢
2nd Quintile $ 48,500 11¢ 12¢
3rd Quintile $ 59,500 19¢ 19¢
4th Quintile $ 92,842 35¢ 39¢
Richest 20% $ 208,023 31¢ 35¢
Source: Orzechowski & Sepielli 2003, U.S. Census
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Distinctive Social Exposures
The added burden of racism
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Racism and Health: Mechanisms
• Institutional discrimination can restrict socioeconomic attainment and group differences in SES and health.
• Segregation can create pathogenic residential conditions.
• Discrimination can lead to reduced access to desirable goods and services.
• Internalized racism (acceptance of society’s negative characterization) can adversely affect health.
• Racism can create conditions that increase exposure to traditional stressors (e.g. unemployment).
• Experiences of discrimination may be a neglected psychosocial stressor.
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Perceived Discrimination:
Experiences of discrimination are a neglected psychosocial stressor
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Discrimination Persists
• Pairs of young, well-groomed, well-spoken college men with identical resumes apply for 350 advertised entry-level jobs in Milwaukee, Wisconsin. Two teams were black and two were white. In each team, one said that he had served an 18-month prison sentence for cocaine possession.
• The study found that it was easier for a white
male with a felony conviction to get a job than a black male whose record was clean.
Devah Pager; Am J Sociology, 2004
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Percent of Job Applicants Receiving a Callback
Criminal Record White Black
No 34% 14%
Yes 17% 5%
Devah Pager; Am J Sociology, 2004
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Race, Criminal Record, and Entry-level Jobs in NY, 2004
1315
17
0
10
20
White felon Latino (clean record) Black (clean record)
Posi
tive
Res
pons
e (%
)
Devah Pager et al Am Soc Review, 2009; 169 employers
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Perceived Discrimination and Health • Discrimination is associated with elevated risk of -- diabetes risk (Hemoglobin A1c) -- substance use (smoking, alcohol, other drugs) -- breast cancer incidence -- uterine myomas (fibroids) -- subclinical carotid artery disease (IMT; intima-
media thickness -- Delays in seeking treatment, lower adherence to
treatment regimes, lower rates of follow-up • Discrimination accounts, in part, for racial/ethnic
disparities in health, in U.S., and elsewhere
Williams & Mohammed, J Behav Med 2009
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Every Day Discrimination In your day-to-day life how often have any of the following things happened to you?
• You are treated with less courtesy than other people. • You are treated with less respect than other people. • You receive poorer service than other people at restaurants
or stores. • People act as if they think you are not smart. • People act as if they are afraid of you. • People act as if they think you are dishonest. • People act as if they’re better than you are. • You are called names or insulted. • You are threatened or harassed. What do you think was the main reason for these experiences?
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• Everyday Discrimination: positively associated with: -- coronary artery calcification (Lewis et al., Psy Med, 2006)
-- C-reactive protein (Lewis et al., Brain Beh Immunity, 2010)
-- blood pressure (Lewis et al., J Gerontology: Bio Sci & Med Sci 2009)
-- lower birth weight (Earnshaw et al., Ann Beh Med, 2013)
-- cognitive impairment (Barnes et al., 2012)
-- poor sleep [object. & subject.] (Lewis et al, Hlth Psy, 2012)
-- mortality (Barnes et al., J Gerontology: Bio Sci & Med Sci, 2008).
-- visceral fat (Lewis et al., Am J Epidemiology, 2011)
Discrimination & Health: Tene Lewis et al
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Distinctive Social Exposures
Place Matters! Geographic location determines
exposure to risk factors and resources that affect health
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White Women
Heart Disease Rates Mississippi 1996-2000
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Black Women
Heart Disease Rates Mississippi 1996-2000
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Women
Heart Disease Rates Mississippi 1996-2000
Black White
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Residential Segregation is a
place-based example of Institutional Discrimination that has pervasive adverse effects on
health
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Racial Segregation Is … 1. Myrdal (1944): …"basic" to understanding racial
inequality in America. 2. Kenneth Clark (1965): …key to understanding racial
inequality. 3. Kerner Commission (1968): …the "linchpin" of U.S.
race relations and the source of the large and growing racial inequality in SES.
4. John Cell (1982): …"one of the most successful political ideologies" of the last century and "the dominant system of racial regulation and control" in the U.S.
5. Massey and Denton (1993): …"the key structural factor for the perpetuation of Black poverty in the U.S." and the "missing link" in efforts to understand urban poverty.
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How Segregation Can Affect Health
1. Segregation determines SES by affecting quality of education and employment opportunities.
2. Segregation can create pathogenic neighborhood and housing conditions.
3. Conditions linked to segregation can constrain the practice of health behaviors and encourage unhealthy ones.
4. Segregation can adversely affect access to medical care and to high-quality care.
Source: Williams & Collins , 2001
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© 2008 Robert Wood Johnson Foundation. All rights reserved.
Our Neighborhood Affects Our Health
Unhealthy Community Healthy Community vs
Exposure to toxic air, hazardous waste Clean air and environment
Unsafe even in daylight Safe neighborhoods, safe schools, safe walking routes
No parks/areas for physical activity
Well-equipped parks and open/spaces/organized community recreation
Limited affordable housing is run-down; linked to crime
ridden neighborhoods
High-quality mixed income housing, both owned and
rental
Convenience/liquor stores, cigarettes and liquor
billboards, no grocery store
Well-stocked grocery stores offering nutritious foods
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© 2008 Robert Wood Johnson Foundation. All rights reserved.
Our Neighborhood Affects Our Health
Burned-out homes, littered streets
Well-kept homes and tree-lined streets
Streets and sidewalks in disrepair
Clean streets that are easy to navigate
No culturally sensitive community centers, social services or opportunities to engage with neighbors in community
life
Organized multicultural community programs, social services, neighborhood
councils or other opportunities for participation in community life
No local health care services Primary care through
physicians’ offices or health center; school-based health
programs
Lack of public transportation, walking or biking paths
Accessible, safe public transportation, walking and
bike paths
Unhealthy Community Healthy Community vs
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Residential Segregation and SES A study of the effects of segregation on young African American adults found that the elimination of segregation would erase black-white differences in Earnings High School Graduation Rate Unemployment
And reduce racial differences in single motherhood by two-thirds
Cutler, Glaeser & Vigdor, 1997
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Segregation and Medical Care -I
• Pharmacies in segregated neighborhoods are less likely to have adequate medication supplies (Morrison et al. 2000)
• Hospitals in black neighborhoods are more likely to close (Buchmueller et al 2004; McLafferty, 1982; Whiteis, 1992).
• MDs are less likely to participate in Medicaid in racially segregated areas. Poverty concentration is unrelated to MD Medicaid participation (Greene et al. 2006)
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Segregation and Medical Care -II • Blacks are more likely than whites to reside
in areas (segregated) where the quality of care is low (Baicker, et al 2004).
• African Americans receive most of their care from a small group of physicians who are less likely than other doctors to be board certified and are less able to provide high quality care and referral to specialty care (Bach, et al. 2004).
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Racial Differences in Residential Environment
• In the 171 largest cities in the U.S., there is not even one city where whites live in ecological equality to blacks in terms of poverty rates or rates of single-parent households.
• “The worst urban context in which whites reside is considerably better than the average context of black communities.” p.41
Sampson & Wilson 1995
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American Apartheid: South Africa (de jure) in 1991 & U.S. (de facto) in
2000 82 81 80 80 77
66
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New Y
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Massey 2004; Iceland et al. 2002; Glaeser & Vigdor 2001
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Research Implications: Distinctive Patterns? • What effects do these distinctive residential
environments have on normal physiological processes?
• How are normal adaptive and regulatory systems affected by the harsh residential environment of blacks and other minorities?
• To what extent does African Americans’ biological adaptation to their residential environments lead to some biological profiles that are different from other groups and some distinctive patterns of interactions (between biological and psychosocial factors)?
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Understanding the Social Environment “Any successful attempt to constructively
leverage the remarkable advances of the genomic era will depend upon our ability to understand genetic influences and their interactions with the environmental context within which they operate.”
Michael J. Meaney
Child Development, 2010
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Gene-Environment Interactions • Future Genomic research needs to give increased
attention to the comprehensive, detailed, and rigorous characterization of the risk factors/resources in the psychological, social, chemical and physical environment that may interact with genetic to affect health risk
• Much of the research to date on race and genetics has, emphasized gene frequency differences over gene expression differences. Given racial and SES differences in residential and occupational environments, more systematic attention should be given to understanding the contribution of epigenetics to disease risk.
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Social Environment and Epigenetic Changes By analyzing the brain tissue from adults who had
committed suicide, one study found genetic changes in those who had been abused as a child. That is, hippocampal gene expression was decreased in victims of child abuse compared to controls with no abuse.
Another study found changes in prostate gene expression among men with low-risk prostate cancer in response to lifestyle changes in diet, exercise, stress management and social support.
Several studies have linked adverse social conditions in early life with adult differences in gene expression in the cells of the immune system. Confirmed in randomized experiment with rhesus macaques McGowan et al. Nature Neuro 2009 ; Ornish et al. Proc Natl Acad Sci 2008; Cole et al. PNAS, in
press
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Research Challenge We need a more integrated science to better elucidate: • how individuals zip code interacts with their genetic
code to affect health risks? • how do multiple dimensions of the social and
physical environment, -- combine, additively and/or interactively with
each other, -- and with innate and acquired biological factors,
-- and accumulate over the life course, -- to affect the onset of illness -- and the progression of disease processes
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Concluding Thoughts First, many non-genetic factors contribute to health
disparities. Racial groups differ on a broad range of environmental risks and exposures
Second, we need trans-NIH initiatives to develop improved definitions and measurement of the social environment in all of its complexity
Third, gene-environmental interactions are central to understanding the role of genomics in disease. We need better integration of social environmental exposures with innate and acquired biological factors
Fourth, conclusions about the contribution of genetics should be based on direct tests of genetic traits Williams et al. 2010 Ann NY Acad Sci
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Concluding Thoughts -II Fifth, research on race and genetics should exercise
caution in making generalizations and inferences to entire “racial” populations when coverage of the diverse ancestral groupings is limited
Sixth, given the distinctive environments of racial minorities in the U.S., more systematic attention should be given to identifying and understanding potential epigenetic effects.
Finally, more attention needs to be given now to ensure that the full potential of genomics becomes accessible to all. This will require reforming current infrastructures and developing best practices Williams et al. 2010 An NY Acad Sci