TY - JOUR
T1 - Methods for detecting interactions between genetic polymorphisms and prenatal environment exposure with a mother-child design
AU - Wang, Shuang
AU - Zheng, Tian
AU - Chanock, Stephen
AU - Jedrychowski, Wieslaw
AU - Perera, Frederica P.
PY - 2010/2
Y1 - 2010/2
N2 - Prenatal exposures such as polycyclic aromatic hydrocarbons and early postnatal environmental exposures are of particular concern because of the heightened susceptibility of the fetus and infant to diverse environmental pollutants. Marked interindividual variation in response to the same level of exposure was observed in both mothers and their newborns, indicating that susceptibility might be due to genetic factors. With the mother-child pair design, existing methods developed for parent-child trio data or random sample data are either not applicable or not designed to optimally use the information. To take full advantage of this unique design, which provides partial information on genetic transmission and has both maternal and newborn outcome status collected, we developed a likelihood-based method that uses both the maternal and the newborn information together and jointly models gene-environment interactions on maternal and newborn outcomes. Through intensive simulation studies, the proposed method has demonstrated much improved power in detecting gene-environment interactions. The application on a real mother-child pair data from a study conducted in Krakow, Poland, suggested four significant gene-environment interactions after multiple comparisons adjustment.
AB - Prenatal exposures such as polycyclic aromatic hydrocarbons and early postnatal environmental exposures are of particular concern because of the heightened susceptibility of the fetus and infant to diverse environmental pollutants. Marked interindividual variation in response to the same level of exposure was observed in both mothers and their newborns, indicating that susceptibility might be due to genetic factors. With the mother-child pair design, existing methods developed for parent-child trio data or random sample data are either not applicable or not designed to optimally use the information. To take full advantage of this unique design, which provides partial information on genetic transmission and has both maternal and newborn outcome status collected, we developed a likelihood-based method that uses both the maternal and the newborn information together and jointly models gene-environment interactions on maternal and newborn outcomes. Through intensive simulation studies, the proposed method has demonstrated much improved power in detecting gene-environment interactions. The application on a real mother-child pair data from a study conducted in Krakow, Poland, suggested four significant gene-environment interactions after multiple comparisons adjustment.
KW - Gene-environment interaction
KW - Likelihood ratio test
KW - Mother-child pair design
UR - http://www.scopus.com/inward/record.url?scp=76649101056&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=76649101056&partnerID=8YFLogxK
U2 - 10.1002/gepi.20441
DO - 10.1002/gepi.20441
M3 - Article
C2 - 19582785
AN - SCOPUS:76649101056
VL - 34
SP - 125
EP - 132
JO - Genetic Epidemiology
JF - Genetic Epidemiology
SN - 0741-0395
IS - 2
ER -