The Biological Determinants of Health & Disease

Internal Agency

Haemodynamics

interaction of biology with environment

"maintenance"

"physiological toll exerted on the body over time by efforts to adapt to life experience"

McEwen

Environmental

Age

haemodynamics

stress

physical inactivity

poor diet

poor environment

Allostatic Load

interfacing

Energetic Stimulation

Fuel

&

better predictor of cognitive decline and cardiovascular performance in older persons than more standard parameters-Seeman et al 1997

nutrition

stress

• cardiovascular vulnerability
• high blood pressure
• insulin resistance
• central adiposity
• immunologic susceptibility

• too much

• too little

disuse

• cardiovascular vulnerabilty
• musculoskeletal fragility
• immunologic susceptibility
• metabolic instability
• depression
• precocious aging

VO2 max (max o2 uptake)-declines 4 times faster in an unfit person

overweight &

obesity

diet as marker of environment

underweight &

malnutrition

most important determinant of mortality

chronological age = biological aging + life experiences

inevitable decline in function in 12 organ systems from the age of 30

allostatic load

0.5%/year

Mortality by age in Ireland

age

mortality

lifecourse approach

health = risk behaviours + protective factors + environmental agents

adulthood

childhood

pre-birth

infancy

adolescence

later life

permanent

reduction

in muscle cell

numbers

compensatory

hypertrophy

of muscle

adaptive

processes

begin to fail

Health

poor intrauterine

environment

modifiers

physiological or metabolic stressors or protective factors

can affect function or structure

Chronic Disease

Respiratory Disease

poor educational

attainment

poor adult

SES

poor

childhood

SES

accumulating advantage exercise

occupational hazards

air pollution

poor adult diet

smoking

air pollution

passive smoking

poor nutrition

childhood

respiratory

illness

infant respiratory

infections

rapid decline in lung function/ ADULT RESPIRATORY DISEASE

poor growth

in utero

poor lung

development

dominant influence

biological

social

socio-biological

asthmatic tendency or genetic predisposition

bio-social

Lifecourse + Epigenetics

Low Birth Weight

• 20 time increase in mortality and morbidity
• associated with chronic diseases in later life

Biological Determinants of

Health & Disease

Leading Causes of Death in Ireland 2010

Top 10 Risk Factors for Global Burden of Disease:

WHO 2009

Markers of Risk

What is a determinant?

association

cause

effect

environment

statistical relationship between factors

unit of heredity

COPD

cigarette

lighters

=long strands of DNA

salt intake

smoking

heart disease

baldness

vs.

physical activity

3rd factor

Genes

causation

Epidemiological Triad

Rothmans model

smoking and lung cancer

Sufficient cause (the whole pie)

• a set of conditions without any one of which the disease would not have occurred (PCP pneumonia)

Component cause (pie wedge)

• Any one of the set of conditions necessary (immune deficiency)

Necessary cause

• a component cause that is necessary for development of disease (pneumocystis carinii)

Stroke

High Blood Pressure

central adiposity

Body of Evidence Approach

Bradford Hill Causal Criteria 1965

• Strength of association
• Consistency
• Specificity
• Temporality
• Biological Gradient
• Plausibility
• Coherence
• Experiment
• Analogy

genetics

genome=2 sets of 23 chromosomes (approx. 30,000 genes)

measurable nodes within the web of causation, rather than independent causes

Biological markers of risk

• modifiable/non modifiable
• proximal/distal (time or place)

genetic expression

world

culture

community

family

individual

systemic

histological

cellular

molecular

Cancers

Cardiovascular Disease

Risk Factors

environmental

Classical Inheritance (Mendelian)

differences in genotype

phenotype

pollutants (air, water, pesticides, hormones, drugs)

infectious diseases (Hep. B/HPV)

radiation

occupational exposure (asbestos)

smoke (passive smoking/indoor cooking/fires)

gg, GG

alleles

Single-Gene Diseases

homozygous

heterozygous

(set of genetic information)

Gg or gG

Risk Factors for MI

Heredity

G

H (straight)

G

g

• PKU (Phenylketonuria)
• Cystic Fibrosis
• Huntington's Chorea
• Sickle Cell Anaemia
• Familial Hypercholesterolaemia

dominant

recessive

h (bent)

g

Gg

GG

G

behavioural

g

<2% of diseases are purely hereditary

gg

gG

smoking

diet

alcohol

infectious diseases (HPV)

HH, Hh, hH

hh

high cholesterol

abdominal obesity

genetic

ethnicity (CLL rare in Asians)

high blood pressure

• smoking
• high cholesterol
• abdominal obesity
• high blood pressure
• psychological (stress)
• nutrition
• physical inactivity

phenotype (traits)

familial

psychological

+

Familial

exposure

susceptibility

1/12 women in UK

15% Positive Family History

5% identifiable genetic cause

(BRCA1&2, AT Mutation, HRAS 1)

observable

• Breast
• Colon
• Retinoblastoma
• Wilm's tumour

Gene-Environment Interaction

Models:

risk

Additive

exposure

99.9%

98%

proportional increase in risk moving from protective to high risk environment

95%

Exposure

genes influence exposure to high risk environment

• physical
• behavioural
• risk markers

multiple genes & environmental impact

Multiplicative

differential response to high risk environment

high risk environment brings out genetic susceptibility

Genetic Polymorphism

Physical

Activity

Cardiovascular Disease

Age

Type 2

Diabetes

Fat Intake

Risk Continuum

• genetic contribution-multiple genes
• multiplicative gene-environment pattern

CVD

Cholesterol

Education

Weight

Distribution of BMI for 2 environments

(healthy)

A-no genetic susceptibility

B-genetic susceptibility

A'-no genetic susceptibility

B'-genetic susceptibility

(Obesogenic')

Income

Blood Pressure

Alcohol

Smoking

Epigenetics

epigenome-determines gene expression

reacts to environmental signals

Biological Determinants of Health and Disease Framework

epigenomic inheritance-inheritance of tags that affect

gene expression(growth & metabolism)

Design

Genes

XX=female

Gender

XY=male

X,Y Chromosomes

Age

Age Specific Mortality

Leading causes of death

CVD/cancer

Cancer/CVD

Injury & Poisoning/cancer

RTA's

2(m):1(f)

Suicides

3-4 (m):1(f)

Injury & Poisoning/cancer

Prenatal conditions/congenital

anomalies

Internal Agents

Maintenance

Gender differences

• biology

specific cancers/hormonal effects

• use of services
• access to services
• social categorization

(External Agents)

Accidents

“People are born female and male, but learn to be girls and boys who grow into women and men.

They are taught appropriate behaviour

and attitudes, roles and activities for them.

This learned behaviour is what makes up gender identity and what makes up gender”

percentage of smokers by age, gender and social class 2007

Race

vs.

Ethnicity

includes cultural, social and economic dimensions

set of biological characteristics

typically adult onset and obesity related

Non Insulin Dependent Diabetes

liver and muscle resistance to insulin

Pima Indians (Native American)

>50% of adult population

genetic predisposition

populations with higher mixture of Native American genes have higher rates of diabetes

ethnic component

marginalisation, deprivation & poverty

low socioeconomic status

obesity (reduced access to healthy food, reduced opportunities for exercise

overproduction of cortisol

(central adiposity)

chronic stress

genetic susceptibility unmasked by poor environment

environment defined by ethnicity (in this case)

Dr. Geraldine McDarby

Geraldine.McDarby@nuigalway.ie