Genome-Wide Association Analysis of Soluble ICAM-1 Concentration Reveals Novel Associations at the NFKBIK, PNPLA3, RELA, and SH2B3 Loci

Soluble ICAM-1 (sICAM-1) is an endothelium-derived inflammatory marker that has been associated with diverse conditions such as myocardial infarction, diabetes, stroke, and malaria. Despite evidence for a heritable component to sICAM-1 levels, few genetic loci have been identified so far. To comprehensively address this issue, we performed a genome-wide association analysis of sICAM-1 concentration in 22,435 apparently healthy women from the Women's Genome Health Study. While our results confirm the previously reported associations at the ABO and ICAM1 loci, four novel associations were identified in the vicinity of NFKBIK (rs3136642, P = 5.4×10−9), PNPLA3 (rs738409, P = 5.8×10−9), RELA (rs1049728, P = 2.7×10−16), and SH2B3 (rs3184504, P = 2.9×10−17). Two loci, NFKBIB and RELA, are involved in NFKB signaling pathway; PNPLA3 is known for its association with fatty liver disease; and SH3B2 has been associated with a multitude of traits and disease including myocardial infarction. These associations provide insights into the genetic regulation of sICAM-1 levels and implicate these loci in the regulation of endothelial function

Antenatal magnesium individual participant data international collaboration: assessing the benefits for babies using the best level of evidence (AMICABLE)

BACKGROUND: The primary aim of this study is to assess, using individual participant data (IPD) meta-analysis, the effects of administration of antenatal magnesium sulphate given to women at risk of preterm birth on important clinical outcomes for their child such as death and neurosensory disability. The secondary aim is to determine whether treatment effects differ depending on important pre-specified participant and treatment characteristics, such as reasons at risk of preterm birth, gestational age, or type, dose and mode of administration of magnesium sulphate. METHODS: Design: The Antenatal Magnesium Individual Participant Data (IPD) International Collaboration: assessing the benefits for babies using the best level of evidence (AMICABLE) Group will perform an IPD meta-analysis to answer these important clinical questions. Setting/Timeline: The AMICABLE Group was formed in 2009 with data collection commencing late 2010. Inclusion Criteria: Five trials involving a total 6,145 babies are eligible for inclusion in the IPD meta-analysis. Primary study outcomes: For the infants/children: Death or cerebral palsy. For the women: Any severe maternal outcome potentially related to treatment (death, respiratory arrest or cardiac arrest). DISUCSSION: Results are expected to be publicly available in 2012.C.A. Crowther, P.F. Middleton, L.M. Askie, L.W. Doyle, T.K. Bubner and M. Voyse