graphical models for combining multiple sources of information in observational studies nicky best...
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Graphical models for combining multiple sources of information in
observational studies
Nicky BestSylvia Richardson
Chris JacksonVirgilio GomezSara Geneletti
ESRC National Centre for Research Methods – BIAS node
Outline
• Overview of graphical modelling• Case study 1: Water disinfection byproducts and
adverse birth outcomes – Modelling multiple sources of bias in observational
studies
• Bayesian computation and software• Case study 2: Socioeconomic factors and heart
disease (Chris Jackson)– Combining individual and aggregate level data– Application to Census, Health Survey for England, HES
Graphical modelling
Modelling
Inference
Mathematics
Algorithms
1. Mathematics
Modelling
Inference
Mathematics
Algorithms
• Key idea: conditional independence• X and W are conditionally independent given Z if, knowing
Z, discovering W tells you nothing more about XP(X | W, Z) = P(X | Z)
Example: Mendelian inheritance• Y, Z = genotype of parents • W, X = genotypes of 2 children• If we know the genotypes of the parents, then the
children’s genotypes are conditionally independent
P(X | W, Y, Z) = P(X | Y, Z)
Y
W
Z
X
Joint distributions and graphical models
Graphical models can be used to:
• represent structure of a joint probability distribution…..
• …..by encoding conditional independencies
Factorization thm:
Jt distribution P(V) = P(v | parents[v])
Y
W
Z
XP(X|Y, Z)P(W|Y, Z)
P(Z)P(Y)
P(W,X,Y,Z) = P(W|Y,Z) P(X|Y,Z) P(Y) P(Z)
Where does the graph come from?
• Genetics– pedigree (family tree)
• Physical, biological, social systems– supposed causal effects (e.g. regression models)
• Conditional independence provides basis for splitting large system into smaller components
Y
W
Z
X
A B
D
C
• Conditional independence provides basis for splitting large system into smaller components
Y
W
Z
WD
C
Y Z
X
Y
A B
2. Modelling
Modelling
Inference
Mathematics
Algorithms
Building complex models
Key idea• understand complex system• through global model• built from small pieces
– comprehensible– each with only a few variables– modular
Example: Case study 1
• Epidemiological study of low birth weight and mothers’ exposure to water disinfection byproducts
• Background– Chlorine added to tap water supply for disinfection– Reacts with natural organic matter in water to form
unwanted byproducts (including trihalomethanes, THMs)– Some evidence of adverse health effects (cancer, birth
defects) associated with exposure to high levels of THM– SAHSU are carrying out study in Great Britain using
routine data, to investigate risk of low birth weight associated with exposure to different THM levels
Data sources
• National postcoded births register• Routinely monitored THM concentrations in tap
water samples for each water supply zone within 14 different water company regions
• Census data – area level socioeconomic factors• Millenium cohort study (MCS) – individual level
outcomes and confounder data on sample of mothers
• Literature relating to factors affecting personal exposure (uptake factors, water consumption, etc.)
Model for combining data sources
[c]
[T]
yik
2
yim
cik
i
cim
THMik[mother]
THMzt[true]
THMztj[raw]
THMim[mother]
Regression sub-model (MCS)
[c]
[T]
yik
2
yim
cik
i
cim
THMik[mother]
THMzt[true]
THMztj[raw]
THMim[mother]
Regression model for MCS data relating risk of low
birth weight (yim) to mother’s THM exposure
and other confounders (cim)
Regression sub-model (MCS)
[c]
[T]
yim
cim
THMim[mother]
Regression model for MCS data relating risk of low
birth weight (yim) to mother’s THM exposure
and other confounders (cim)
Logistic regression
yim ~ Bernoulli(pim)
logit pim = b[c] cim + b[T] THMim
i indexes small area
m indexes mother
[mother]
cik = potential confounders,e.g. deprivation, smoking, ethnicity
Regression sub-model (national data)
[c]
[T]
yik
2
yim
cik
i
cim
THMik[mother]
THMzt[true]
THMztj[raw]
THMim[mother]
Regression model for national data relating risk of
low birth weight (yik) to mother’s THM exposure
and other confounders (cik)
Regression sub-model (national data)
[c]
[T]
yik
cik
THMik[mother]
Regression model for national data relating risk of
low birth weight (yik) to mother’s THM exposure
and other confounders (cik)
Logistic regression
yik ~ Bernoulli(pik)
logit pik = b[c] cik + b[T] THMik
i indexes small areak indexes mother
[mother]
Missing confounders sub-model
[c]
[T]
yik
2
yim
cik
i
cim
THMik[mother]
THMzt[true]
THMztj[raw]
THMim[mother]
Missing data model to estimate confounders (cik)
for mothers in national data, using information on within area distribution of
confounders in MCS
Missing confounders sub-model
cik
i
cim
Missing data model to estimate confounders (cik)
for mothers in national data, using information on within area distribution of
confounders in MCS
cim ~ Bernoulli(i) (MCS mothers)
cik ~ Bernoulli(i) (Predictions for
mothers in national data)
THM measurement error sub-model
[c]
[T]
yik
2
yim
cik
i
cim
THMik[mother]
THMzt[true]
THMztj[raw]
THMim[mother]
Model to estimate true tap water THM concentration
from raw data
THM measurement error sub-model
2
THMzt[true]
THMztj[raw]
Model to estimate true tap water THM concentration
from raw data
THMztj ~ Normal(THMzt, 2)
z = water zone; t = season; j = sample
(Actual model used was a more complex mixture of Normal distributions)
[raw] [true]
THM personal exposure sub-model
[c]
[T]
yik
2
yim
cik
i
cim
THMik[mother]
THMzt[true]
THMztj[raw]
THMim[mother]
Model to predict personal exposure using estimated tap water THM level and
literature on distribution of factors affecting individual
uptake of THM
THM personal exposure sub-model
THMik[mother]
THMzt[true]
THMim[mother]
Model to predict personal exposure using estimated tap water THM level and
literature on distribution of factors affecting individual
uptake of THM
THM = ∑k THMzt x quantity (1k) x uptake factor (2k)
where k indexes different water use activities, e.g. drinking, showering, bathing
[mother] [true]
3. Inference
Modelling
Inference
Mathematics
Algorithms
Bayesian
… or non Bayesian
• Graphical approach to building complex models lends itself naturally to Bayesian inferential process
• Graph defines joint probability distribution on all the ‘nodes’ in the model
Recall: Joint distribution P(V) = P(v | parents[v])
• Condition on parts of graph that are observed (data) • Calculate posterior probabilities of remaining nodes
using Bayes theorem• Automatically propagates all sources of uncertainty
Bayesian Full Probability Modelling
[c]
[T]
yik
2
yim
cik
i
cim
THMik[mother]
THMzt[true]
THMztj[raw]
THMim[mother]
Data
Unknowns
4. Algorithms
Modelling
Inference
Mathematics
Algorithms
• MCMC algorithms are able to exploit graphical structure for efficient inference
• Bayesian graphical models implemented in WinBUGS