Transcript Social Genomics

Anita R. Webb, PhD
JPS Health Network
Fort Worth, Texas
[email protected]
SOCIAL GENOMICS
Goals/Objectives
 Preview a relatively new field of genetics.
 Explore effects of environmental factors on
gene expression.
 Review examples of research in this arena.
 Consider implications for family physicians.
Main Points
 Environmental factors can affect gene
expression.
 The environment, including the social
environment, can ultimately determine
genetic profiles.
 New explanations are emerging for chronic
medical problems.
PREMISE
 “It has become increasingly clear that
social factors can play a significant role
in regulating the activity of human genes.”
 Cole, SW. Social regulation of human
gene expression. Curr Dir Psychol Sci.
2009; 18(3): 132–137.
BASICS
 Cells are highly selective about which
genes they express.
 The expression of a specific gene is often
more an exception than the rule.
 The social world influences which genes are
transcribed within the nuclei of our cells.
 Ibid.
For Example
 “Social stress and isolation have long been known
to affect the onset and progression of disease .”
 Especially viral infections
 Social factors have been linked to
 Rhinoviruses
 AIDS virus
 Several cancer-related viruses
 Ibid.
Classic Study
 Medical students’ health in reaction
to course exams
 More “colds” preceding exams.
 Sheldon Cohen, Ph.D., David A.J. Tyrrell, M.D.,
and Andrew P. Smith, Ph.D. Psychological stress
and susceptibility to the common cold. N Eng J
Med. 1991; 325:606-612.
Social Regulation of Gene
Expression
 “Several studies have shown that social
influences can penetrate remarkably deeply
into our bodies.”
 “Key immune system genes are also sensitive
to social conditions.”
 Sloan EK, et al. Social stress enhances sympathetic
innervation of primate lymph nodes: mechanisms
and implications for viral pathogenesis. J Neurosci.
2007; 27(33):8857–8865.
Social Factors and Genetics
 “Early experience affects every aspect of behavior
and biology, including gene expression.”
 “The environment can affect genes”
 “Forcing some to turn on and others to turn off.”
 Cacioppo JT, Hawkley LC, Crawford LE, et al. Loneliness
and Health: Potential Mechanisms. Psychosomatic Med.
2002;64(3), 407-417.
TOPICS
 I. Pregnancy: “Fetal Origins”


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A. Birth weight
B. Maternal obesity, diabetes
C. Maternal malnutrition: Starvation
D. Maternal stress, depression
E. Maternal environment: Air pollution
 II. Childhood environment and experiences
I. PREGNANCY
 Known: Mother’s environment impacts fetus.
 “Biological postcards from the world outside”
 Food, drink, air quality, common chemicals,
medications, emotions, activity, toxins, etc.
 Continue to affect health into adulthood
 Paul, AM. Origins: How the nine months before birth
shape the rest of our lives. NY: Simon & Schuster/Free
Press, 2010.
Prenatal Origins of Adult Disease
 Heart Disease Study (Britain, N = 15,000)
 Highest rates found in poorest regions
 Correlate finding: Small birth size
 Hypothesis: Inadequate prenatal nutrition?
 Suggested: Heart disease due to prenatal factor
 Poor nutrition during gestation
 DJP Barker. Developmental origins of adult disease.
Euro J Epidem 2003; 18(8):733-736.
Birth Weight and Adult Health
 Nurses’ Health Study (Boston)
 Longitudinal: 1976-1997, N=121,700
 Birth weight and mortality
 INVERSELY associated for:
 Cardiovascular disease
 Coronary heart disease
 Stroke
 Rich-Edwards J. Birth weight and risk of cardiovascular
disease in a cohort of women followed up since 1976.
BMJ 1997;315:396.
Nurses Study (continued)
 Largely independent of
 Adult weight
 Hypertension
 Diabetes
 And NOT related to
 Childhood socioeconomic status or
 Adult lifestyle
Birth Weight and Diabetes
 Low birth weight
 Increased the risk for DIABETES
 As an adult.
 Jimenez-Chillaron, JC. β-Cell Secretory Dysfunction
in the Pathogenesis of Low Birth Weight–Associated
Diabetes. Diabetes, March 2005; 54 (3): 702-711.
Pregnancy Weight Gain
 Mother’s weight gain during pregnancy
 The greater her weight gain,
 The higher the risk that
 The child would be overweight by age 3.
 Kral J, et al. Large maternal weight loss from obesity
surgery prevents transmission of obesity to children
who were followed for 2 to 18 years. Pediatrics, 118 #6.
Dec 1, 2006 pp. e1644 -e1649
Obesity (cont.)
 Siblings born after the
 Mother’s bariatric surgery and
 Subsequent weight loss
 Had lower birth weights and
 Were 52% less likely to become obese
 Compared to their older siblings who were
born prior to mother’s bariatric surgery
 Ibid.
Childhood Obesity
 Mechanism:
 Post-surgery babies processed fats and
carbohydrates in a healthier way.
 The risk for childhood obesity
 May be programmed in the womb
 By mother’s pregnancy weight gain.
 Ibid.
Maternal DIABETES




Known: Significant genetic factor for diabetes
?: Effect of mother’s high blood sugar on fetus?
Longitudinal study with Pima Indians (AZ)
Conclusion:
 “Exposure to maternal diabetes in utero
 “Accounts for most of the type 2 diabetes
 “Among Pima children over the past 30 years.”
 Dabelea, Knowles, Pettitt . Effect of diabetes in pregnancy
on offspring: Follow-up research in the Pima Indians. J
Mat-Fetal Neonatal Med 2000; 9(1): 83-88.
Pregnancy Nutrition
 Research with pregnant mice
 Fed cruciferous vegetables (broccoli, cabbage)
 Decreased cancer risk in offspring
 Following exposure to a known carcinogen
 Healthy nutrition conferred
 “Lifelong chemo-protection”
 http://www.sciencedirect.com/science/article/pii/
S1043661807000321
Pregnancy Malnutrition
 Extreme example: Starvation
 Crop failures, food blockades during wars
 Offspring had higher risk for schizophrenia
 Maternal malnutrition may disrupt neural
development of fetus.
 Smith, CA. Effect of wartime starvation in Holland upon
pregnancy and its product. Am J Obstet Gynecol.
1947;53(4):599-608.
 [Also: famine during China’s “Great Leap Forward”]
Maternal Stress
 Stress hormones may impact intrauterine
environment, increasing risk of:
 Premature delivery
 Low birth weight
 May affect fetus’ developing nervous system
 Temperament (e.g. “reactivity”)
 Increased sensitivity to stress
 Increased risk for mental illness
“Fetal Origins” Hypothesis
 Growing body of evidence
 Woman’s distressed mental state during
pregnancy may negatively affect fetus.
 Psychological state during pregnancy can
have effects across the child’s lifespan.
 Kinsella MT, Monk C. Impact of maternal stress,
depression and anxiety on fetal neurobehavioral
development. OB Gyn, Sept 2009, 52 (3): 425-440.
Environmental Toxins
Example: Air Pollution
 Exposure to traffic air pollution during pregnancy
(N=500, New York City)
 Outcomes: Prematurity, heart malformations
 40% of the babies had subtle DNA damage
attributed to the pollution
 Cognitively delayed at age 3, lower IQ at age 5
 F. Perera et al. Effects of transplacental exposure to
environmental pollutants. Environ Health Perspectives
2003; 111 (2):201-205.
“Fetal Origins” of Illness
 Cancer
 Obesity
 Hypertension
 Mental illness
 Cardiovascular
 Arthritis
 Allergies
 Osteoporosis
 Asthma
 Cognitive decline
 (Paul 2010)
 Diabetes
CONVERSELY
It’s frequently the
Intrauterine environment
That makes things go right
In later life.
(Paul 2010)
National Children’s Study
 GOAL: Identify the developmental roots
of health and disease
 N = 10, 000 pregnant women
 Longitudinal: Fetus to age 21
 Federally funded 2009
 First results expected 2012
 Causes of premature birth and birth defects
 http://www.nationalchildrensstudy.gov
Project VIVA
 Effects of childhood experiences on health
 Longitudinal: N = 2000+ children in utero
 Fetal origins of:
 Asthma, Allergies
 Obesity, Heart disease
 Brain development
 Pereira, et al. Predictors of Change in Physical
Activity During and After Pregnancy. Prev Med
2007; 32(4):312-19.
“The New Genetics”
 “Research in social genomics has now clearly
established that our interpersonal world
 “Exerts biologically significant effect s on the
molecular composition of the human body.”
 “Social regulation of human gene expression”
 Cole, SW. Curr Dir Psychol Sci. 2009 June 1; 18(3): 132–137.
 http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3020789/p
df/nihms-257906.pdf
FAMILY PHYSICIANS
 Catbird seat: Prevention agenda
 Patient education and counseling
 Early detection and comprehensive care
 Multi-generational impact of focus on
healthy lifestyle and preventive care
MAIN POINTS
 New explanations are emerging for
chronic medical problems.
 Environmental factors can affect gene
expression and determine phenotype.
 The social environment can ultimately
determine our genetic profile.
 Follow the burgeoning research.
The End