UK IBD twin and multiplex registry: Concordance and environmental risk factors of twins - PowerPoint Presentation

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UK IBD twin and multiplex registry: Concordance and environmental risk factors of twins with IBD Dr Hannah Gordon, Prof Timothy Orchard, Dr Alan Steel, Dr Marcus Harbord

ECCO 2015 Barcelona

Declarations:The authors have no competing interestsFunded by an unrestricted grant from the Jesse and Thomas Tam Family Foundation

Introduction:BackgroundIBD twin studiesMethodsUK IBD Twin and Multiplex RegistryConcordance and environmental risk factorsResultsConclusion

Background:First twin study 1876: ”Nature is far stronger than nurture” (Galton 1876)Classical twin designCompares MZ and DZ concordanceCD and UC both heritable (Tysk 1988, Halfvarson 2007, Brant 2011, Chen 2014)Rate of increase in IBD incidence outweighs genetic drift (

Molodecky 2012)Twin studies provide control for genetic factorsEnvironmental factors

Microbiota and

epigenome

(

Dongen

2012)

Method 1:Recruitment into UK IBD Twin and Multiplex Registry UK research registryTwinsMultiplex (at least 3 first degree)RecruitmentIBD charities (including Royal Free cohort)Clinician referral

Method 2:Inclusion into this analysis TwinsMonozygotic and DizygoticConcordant and DiscordantCrohn’s Disease and Ulcerative Colitis

Method 3:Collecting InformationQUESTIONNAIREDemographicsZygosityConcordanceDisease history (IBD sufferers only)Environmental factorsSmoking (including cannabis)DietStressEarly Environment

MEDICAL RECORDSPrimary care p

hysicians

Gastroenterologist

Disease history

Montreal (CD)

Disease extent (UC)

Medication

Surgical History

Method 4:Data AnalysisPair concordance of MZ and DZ pairsAnalysis of environmental factorsAfter adjusting for correlated data due to comparisons of twins, multivariable mixed-effects logistic regression analysis was performed invoking the GEE method using PROC GENMOD using the repeated statement for twins with logit link

Results 1:Demographics and pair concordanceMean age 57 years (range 21-83)31 MZ:69 DZUC 52: CD 48Pair Concordance:

Crohn’s Disease

Ulcerative Colitis

Monozygotic

53.3%

(8:7)

25% (4:12)

Dizygotic

9.1% (3:30)

19.4% (7:29)

Results 2:Concordance compared with other twin cohortsPair concordance (UK IBD TAM 2014)Previous twin cohorts (Tysk et al 1988,

Halfvarson 2007, Brant 2011)

Crohn’s Disease

Ulcerative

Colitis

Monozygotic

20-55%

3.6-17%

Dizygotic

0-3.6%

0-6.3%

Results 3:Environmental Factors – smoking history

In line with the literature, multivariate analysis suggests

Variable

No.

% CD

N=58

% Non

CD N=38

Odds

Ratio

95% CI

P Value

Smoking

history before diagnosis - CD

No

Yes

Not

Known

58

24

14

34/58 (58.6%)

22/24

(91.7%)

2/14 (14.3%)

24/58

(41.4%)

2/24

(8.3%)

12/14

(85.7%)

Ref

4.11

(1.60 to 10.54)

0.003

Variable

No.

%

UC

N=62

% Non

UC

N=42

Odds

Ratio

95% CI

P Value

Smoking history

before diagnosis - UC

No

Yes

Not

Known

84

10

10

53/84 (63.1%)

7/10

(70%)

3/10

(30%)

31/84

(36.9%)

3/10

(30%)

7/10

(70%)

Ref

0.39

(0.14 to 1.07)

0.067

Results 4:Environmental Factors – Childhood Illness

Variable

N

%IBD

% Non IBD

Odds

ratio

95

% CI

p-value

Childhood illness

Equal

to peers

More than peers

Less than peers

Not Known

115

17

44

24

75(65.2%)

16(94.1%)

26(59.1%)

5(20.8%)

40(34.7%)

1 (5.89%)

18

(40.9%)

19(79.2%)

Ref

7.27

0.79

(1.34 to 39.5)

(0.47 to 1.35)

0.022

0.388

Gastroenteritis

prior to diagnosis

Equal to peers

More than peersLess than peersNot Known12411412483(66.9%)10(90.0%)24(58.5%)5(20.8%)41(33.1%)1(10%)15(41.5%)19(79.2%)Ref2.540.83(0.92 to 7.05)(0.49 to 1.43)0.194

More self reports of frequent childhood illness amongst IBD cohort

Non significant increase in childhood gastroenteritis

Results 5:Environmental Factors - Diet

Variable

Odds

ratio

95% CI

p-value

CD “ready made meals” at least weekly

Yes

4.23

(1.58 to 11.34)

0.017

Univariate analysis significant for CD

Significance lost with correction for multiple comparisons

Results 6:Environmental Factors – Infant Feeding

Limitations:Recall biasPair not proband concordanceSample size

Conclusion:Support heritability CDUC less heritable than other cohorts (Bengtson 2010)SmokingChildhood health

Future Direction:Resource to study interface between genes and environment EpigenomeMicrobiota and metabolomeBiobankInternational CollaborationDenmarkScotland

Questions?hannah.gordon@chelwest.nhs.uk

References:Galton, F. The history of twins, as a criterion of the relative powers of nature and nurture. J. Anthropol. Institute Great Britain Ireland 5, 391–406 (1876)Molodecky et al. Increasing incidence and prevalence of the inflammatory bowel diseases with time, based on systematic review Gastroenterology. 2012 Jan;142(1):46-54.e42Dongen

J, Slagboom P, Draisma H, Martin N, Boomsana DL. The continuing value of twin studies in the omics era. Nat Rev Genet. 2012 Sep;13(9):640-53

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C, Lindberg E,

Jarnerot

G, et al. Ulcerative colitis and Crohn's disease in an unselected population of monozygotic and dizygotic twins. A study of heritability and the influence of smoking. Gut. 1988; 29: 990–996

Halfvarson

J, Jess T,

Bodin

L, et al. Longitudinal concordance for clinical characteristics in a Swedish-Danish twin population with inflammatory bowel disease.

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1536–1544

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2011

Chen GB, Lee SH et al. Estimation

and partitioning of (co)heritability of inflammatory bowel disease from GWAS and

immunochip

data

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Mol

Genet. 2014

May 2

HERITABILITY CALCULATIONS FROM POOLED TWIN DATA WITHIN SUPPLEMENTARY MATERIAL

Bengtson

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G, Vatn MH, Harris JR. Concordance for IBD among twins compared to ordinary siblings – a Nowegian

population based study. J Crohns Colitis. 2010 Sep;4(3):312-8