Evidence for gene-environment interactions in a linkage study of asthma and smoking exposure.
BACKGROUND
Asthma, a common and chronic disease of the airways, has a multifactorial cause involving both genetic and environmental factors. As a result, mapping genes that influence asthma susceptibility has been challenging.


OBJECTIVE
This study tests the hypothesis that inclusion of exposure to environmental tobacco smoke (ETS), a potential risk factor for asthma, would improve the ability to map genes for asthma.


METHODS
By using 144 white families from the Collaborative Study for the Genetics of Asthma, environmental information about exposure to ETS during infancy was incorporated into a genome-wide multipoint linkage analysis. Statistical significance of observed gene-environment interactions was assessed by means of simulation.


RESULTS
Three regions with nominal evidence for linkage when stratified on the basis of ETS exposure were identified (P <.01) and showed a significant increase from the baseline lod score (1p at 97 cM, D1S1669-D1S1665; 5q at 135 cM, D5S1505-D5S816; and 9q at 106 cM, D9S910; all P <.05). In addition, 2 other regions, although not meeting nominal significance after stratification on the basis of ETS exposure, showed a significant increase from baseline lod score when ETS was taken into account (1q at 240 cM, D1S549; 17p at 3 cM, D17S1308; all P <.01).


CONCLUSIONS
These results illustrate how evidence for linkage of asthma can depend on exposure to an environmental factor, such as ETS. Future linkage analyses should include information on suspected environmental factors for asthma to help target new candidate susceptibility genes for asthma.
Colilla
Susan
S
Department of Human Genetics, The University of Chicago, Chicago, IL 60637, USA.
Nicolae
Dan
D
Pluzhnikov
Anna
A
Blumenthal
Malcolm N
MN
Beaty
Terri H
TH
Bleecker
Eugene R
ER
Lange
Ethan M
EM
Rich
Stephen S
SS
Meyers
Deborah A
DA
Ober
Carole
C
Cox
Nancy J
NJ
D000328:Adult; D001249:Asthma / Q000209:etiology* / Q000235:genetics; D008040:Genetic Linkage; D020022:Genetic Predisposition to Disease; D006801:Humans; D014028:Tobacco Smoke Pollution / Q000009:adverse effects*
D014028:Tobacco Smoke Pollution