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”  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 INVERSELY mortality 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    And NOT related to Childhood socioeconomic status or  Diabetes 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    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.

 Offspring had higher risk for schizophrenia [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  Hypertension  Cardiovascular  Allergies  Asthma  Diabetes  Obesity  Mental illness  Arthritis  Osteoporosis  Cognitive decline  (Paul 2010)

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