NIEHS Statistical Consulting Service

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The biostatisticians participating in the statistical consulting service co-authored several research publications in collaboration with scientists within DIR and outisde the DIR. Manuscripts that were published during this year are listed below and there are several more that are either in preparation or in various stages of the review process. Some examples of our collaborative research are as follows: 1. Jukic et al. (2010,2011) analyzed data from the Early Pregnancy Study. Effects of clinical spontaneous abortion on pituitary function in the subsequent menstrual cycle have been reported, but data are sparse on unrecognized very early loss. In these papers, the authors used daily urine-based hormonal measurements based on the Early Pregnancy Study to compare hormonal patterns and menstrual-cycle characteristics (such as luteal phase length) in cycles following early pregnancy loss. Any effects of early loss on the subsequent cycle are evidently small. In a second set of analyses the authors explored possible determinants of late implantation and slow initial risk of hCG in naturally-conceived pregnancies. Older women tended to have a longer interval from ovulation to implantation, as did smokers. A later implantation has previously been shown to be associated with early pregnancy loss. Excluding the early losses the authors explored factors in relation to the rate of rise of the pregnancy hormone, hCG, with the idea that this rise can serve as a marker for the early growth of the embryo. A number of factors, including maternal smoking and maternal prenatal exposure to DES, were associated with the pattern of increase of hCG. 2. Jugessur et al. (2010,2011) carried out genetic family-based analyses of cases of the birth defect oral clefting based on 357 candidate genes represented by 1536 SNPs for 562 case-parent triads in Norway and 236 triads in Denmark. For maternally-mediated genetic effects the gene FNLB was implicated in both populations for the cleft-palate-only phenotype. Strong and consistent effects were not seen for the other genes. In analyses of effects of the fetally inherited markers, the gene FGF12 was implicated in both populations for the cleft-lip-only phenotype. There was some evidence for IRF6, which had been previously reported as associated with clefting. 3. The NTP has a collaborative agreement with NIOSH and the University of Cincinnati to study the effects of diisocyanate compounds on occupational asthma. In this study, workers with and without occupational asthma have been surveyed, examined by physicians, and genotyped for selected single nucleotide polymorphisms (SNPs) in genes related to immune responses. Bernstein et al. (2011)analyzed the associations between these SNPs and occupational asthma, along with additional information such as smoking habits and exposure intensity and duration.