Twin Studies of Asthma and Allergy

David Duffy

QIMR logo Queensland Institute of Medical Research

The Classical Twin Study

Therefore:

How to Perform a Classical Twin Study

Is height heritable?

twin r for height

Is Total Serum Immunoglobulin E level heritable?

twin r for IgE

Assumptions of the Classical Twin Study

Twin-Adoption Studies

Twin-Family Studies

A Twin-Family study of Asthma

Questionnaire

Twin ATwin BSibling
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 ATwin BSibling
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 times4.7% 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?

MZDZ
Twin ATwin BTwin ATwin B
Wheeze36.4% 36.3% 31.8% 35.1%
Asthma28.2% 27.1% 24.6% 24.7%

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-Female333 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
IgE1Dp1IgE2Dp2
Twin 1logIgE--0.590.230.14
Dpter 0.60--0.210.24
Twin 2logIgE0.660.38--0.68
Dpter 0.480.580.55--
MZ correlations lower triangle

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

Within-individual0.6
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.

CommonSpecific
Trait A C E A E
Wheezing 3406 21 17 23
Hayfever 2728 23 03 19
Dust Allergy 3424 41 -- 02
Eczema 4110 12 00 36

TraitCommonSpecific
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

Bronchial hyperresponsiveness on testing (1992) versus reported frequency of wheezing 1980.
Asthma or wheeze 1980BHR+BHR-Not testedPercent tested
No information 15 (38.5%)249004.0
No symptoms 88 (31.9%)18853934.8
Only as a child35 (53.0%)3122622.6
Occasionally 57 (59.4%)3935021.5
Frequently 70 (92.1%)619428.1

Validation of Questionnaire Diagnosis 2

Positive skin prick test to D pter (1992) versus reported frequency of "dust allergy" and wheeze in 1980.
Dust Allergy 1980SPT+SPT-Percent tested
Proband (wheeze in 1980 or 1988)
No information 13 (56.5)1019.9
No symptoms 76 (52.0)7021.9
Only as a child13 (86.7)231.9
Occasionally 45 (81.2)1024.2
Frequently 96 (82.1)2127.2
Nonproband (denied wheeze 1980/1988)
No information 7 (38.9)113.6
No symptoms 55 (37.9)903.2
Only as a child 2 (66.7)17.3
Occasionally 15 (78.9)44.9
Frequently 9 (64.3)54.1