Twin Studies of Asthma and Allergy

David Duffy

Queensland Institute of Medical Research

The Classical Twin Study

• Monozygotic (MZ) twins genetically identical (R=1, K=1).
• Dizygotic (DZ) twins genetically full-sibs (R=0.5, K=0.25)
• Twins of either zygosity will be similarly correlated in terms of environmental exposures.

Therefore:

• Differences between the MZ and DZ within-pair correlations are genetic, rather than due to familial environmental exposures.

How to Perform a Classical Twin Study

• First catch your twins...schools, registries, clinics
• Assess zygosity
• Measure the phenotype of interest
• Exclude zygosity effects on means and variances
• Compare MZ and DZ twin correlations or concordances

Is height heritable?

Is Total Serum Immunoglobulin E level heritable?

Assumptions of the Classical Twin Study

• MZ and DZ twins are not biologically different from singletons wrt trait
• Parental treatment of MZ twins is not different to that of DZ twins
• MZ versus DZ twin correlation in environmental exposure not relevant

Twin-Adoption Studies

• Ascertain MZ and DZ twins reared apart
• Small sample sizes
• Consistent with studies of twins reared together

Twin-Family Studies

• Study twins and their other relatives
• Check consistency of twin results with those from other family members

A Twin-Family study of Asthma

• Parents of twins born 1979-1988 (ATR) surveyed in 1993
• Reported on twins and two additional siblings
• Responses from 2279 families (out of 3400, 66%)

Questionnaire

		Twin A	Twin B	Sibling
7 Type of delivery
	a Cephalic (normal headfirst)	44%	28%	65%
	b Forceps	21%	17%	20%
	c Caesarian Section	28%	30%	13%
	d Breech	8%	25%	2%
8 Complications
	a Placental Difficulty	16%	24%	11%
	b Umbilical cord complications
	c Breathing problems (asphyxia)
	d Anaemia
10 Birth Weight (in gms)	[Median]	2600	2553	3405

Do Twins Get More Asthma than Singletons?

		Twin A	Twin B	Sibling
1. Has he/she ever suffered from wheezy breathing? (Wheezing is a whistling noise coming from the chest, though it can be heard in the mouth)		34.0%	35.3%	28.3%
2. In the last 12 months, how often has he/she had an episode of wheezing
	any	24%	24%	19%
	more than 12 times	4.7%	4.0%	4.1%
5. Does he/she suffer from rhinitis? (Rhinitis is a runny, itchy nose, often with watery and itchy eyes whe he/she DOES NOT have a cold		12.4%	14.0%	14.1%
7. Has a doctor ever diagnosed him/her as suffering from:
	asthma	26%	26%	21%
	allergic rhinitis	5.4%	6.4%	6.8%

More wheezing, perhaps of a milder nature, but no increase in hayfever.

Do MZ Twins Get More Asthma than DZ Twins?

	MZ		DZ
	Twin A	Twin B	Twin A	Twin B
Wheeze	36.4%	36.3%	31.8%	35.1%
Asthma	28.2%	27.1%	24.6%	24.7%

• Sex and prematurity are the big two predictors of wheezing.
• Maternal smoking during pregnancy lowered birthweight (150 g)
• Smoking did not seem to increase risk of wheezing.
• No effects of zygosity were detected.

MZ and DZ Twin Concordances for Asthma

The probandwise concordance is the estimated recurrence risk:

Group	No. Pairs	Concordance	Risk Ratio
MZ Female	512	80.0%	2.4
MZ Male	473	83.3%	2.1
DZ Female	288	52.1%	1.8
DZ Male	323	57.5%	1.5
DZ Female-Male	509	40.5%	1.5
DZ Male-Female		53.1%	1.5
Sib Male-Male	375	53.2%	1.6
Sib Female-Female	333	52.7%	2.1

Multivariate Twin Analyses

The cross-trait correlations can also be analysed to estimate the genetic and environmental correlations. Here is data from a study of 419 adult twins:

		DZ correlations upper triangle
		IgE1	Dp1	IgE2	Dp2
Twin 1	logIgE	--	0.59	0.23	0.14
	Dpter	0.60	--	0.21	0.24
Twin 2	logIgE	0.66	0.38	--	0.68
	Dpter	0.48	0.58	0.55	--
		MZ correlations lower triangle

The total sIGE - D. pter wheal size correlations are roughly:

Within-individual	0.6
Within-MZ pair	0.4
Within-DZ pair	0.2

Multivariate Twin Analyses: More Phenotypes

Questionnaire data from 3808 adult Australian twin pairs.

Proportion of variation (×100) due to common and trait-specific genetic and unshared environmental risk factors from a biometrical factor model.

	Common			Specific
Trait	A	C	E	A	E
Wheezing	34	06	21	17	23
Hayfever	27	28	23	03	19
Dust Allergy	34	24	41	--	02
Eczema	41	10	12	00	36

Trait	Common			Specific
	A	D	E	A	D	E
Wheezing	08	29	09	16	16	24
Hayfever	18	23	27	00	21	12
Dust Allergy	16	38	28	--	--	18
Sinusitis	30	0	19	07	02	41
Bronchitis	13	0	07	06	00	42

Validation of Questionnaire Diagnosis 1

Validation of Questionnaire Diagnosis 2