Gene-environment interaction in atopic diseases: a population-based twin study of early-life exposures.
BACKGROUND
The development of atopic diseases early in life suggests an important role of perinatal risk factors.


OBJECTIVE
To study whether early-life exposures modify the genetic influence on atopic diseases in a twin population.


METHODS
Questionnaire data on atopic diseases from 850 monozygotic and 2279 like-sex dizygotic twin pairs, 3-9 years of age, from the Danish Twin Registry were cross-linked with data on prematurity, Cesarean section, maternal age at birth, parental cohabitation, season of birth and maternal smoking during pregnancy, from the Danish National Birth Registry. Significant predictors of atopic diseases were identified with logistic regression and subsequently tested for genetic effect modification using variance components analysis.


RESULTS
After multivariable adjustment, prematurity (gestational age below 32 weeks) [odds ratio (OR) = 1.93, confidence interval (CI) = 1.45-2.56], Cesarean section (OR = 1.25, CI = 1.05-1.49) and maternal smoking during pregnancy (OR = 1.70, CI = 1.42-2.04) significantly influenced the risk of asthma, whereas none of the factors were significantly associated with atopic dermatitis and hay fever. Variance components analysis stratified by exposure status showed no significant change in the heritability of asthma according to the identified risk factors.


CONCLUSIONS
In this population-based study of children, there was no evidence of genetic effect modification of atopic diseases by several identified early-life risk factors. The causal relationship between these risk factors and atopic diseases may therefore be mediated via mechanisms different from gene-environment interaction.
Department of Respiratory Medicine, Bispebjerg Hospital, Copenhagen, Denmark.
Niklas
N
Kahr
Vibeke
V
Naeser
Lone Graff
LG
Stensballe
Kirsten Ohm
KO
Kyvik
Axel
A
Skytthe
Vibeke
V
Backer
Klaus
K
Bønnelykke
Simon Francis
SF
Thomsen
D001249:Asthma / Q000453:epidemiology*; D002585:Cesarean Section; D002648:Child; D002675:Child, Preschool; D003718:Denmark / Q000453:epidemiology; D003876:Dermatitis, Atopic / Q000453:epidemiology*; D004200:Diseases in Twins / Q000453:epidemiology*; D005260:Female; D059647:Gene-Environment Interaction; D006801:Humans; D016015:Logistic Models; D008297:Male; D008423:Maternal Age; D011247:Pregnancy; D047928:Premature Birth; D012042:Registries; D006255:Rhinitis, Allergic, Seasonal / Q000453:epidemiology*; D012307:Risk Factors; D012907:Smoking; D014429:Twins, Dizygotic / Q000706:statistics & numerical data; D014430:Twins, Monozygotic / Q000706:statistics & numerical data
asthma; environment; genetics; twin tudy