29 research outputs found
Forecasting of commercial sales with large scale Gaussian Processes
This paper argues that there has not been enough discussion in the field of
applications of Gaussian Process for the fast moving consumer goods industry.
Yet, this technique can be important as it e.g., can provide automatic feature
relevance determination and the posterior mean can unlock insights on the data.
Significant challenges are the large size and high dimensionality of commercial
data at a point of sale. The study reviews approaches in the Gaussian Processes
modeling for large data sets, evaluates their performance on commercial sales
and shows value of this type of models as a decision-making tool for
management.Comment: 1o pages, 5 figure
Genome-wide approach identifies a novel gene-maternal pre-pregnancy BMI interaction on preterm birth
Preterm birth (PTB) contributes significantly to infant mortality and morbidity with lifelong impact. Few robust genetic factors of PTB have been identified. Such ‘missing heritability’ may be partly due to gene × environment interactions (G × E), which is largely unexplored. Here we conduct genome-wide G × E analyses of PTB in 1,733 African-American women (698 mothers of PTB; 1,035 of term birth) from the Boston Birth Cohort. We show that maternal COL24A1 variants have a significant genome-wide interaction with maternal pre-pregnancy overweight/obesity on PTB risk, with rs11161721 (PG × E=1.8 × 10−8; empirical PG × E=1.2 × 10−8) as the top hit. This interaction is replicated in African-American mothers (PG × E=0.01) from an independent cohort and in meta-analysis (PG × E=3.6 × 10−9), but is not replicated in Caucasians. In adipose tissue, rs11161721 is significantly associated with altered COL24A1 expression. Our findings may provide new insight into the aetiology of PTB and improve our ability to predict and prevent PTB.HSN268200782096CHHSN268201200008I20-FY02-56, #21-FY07-605R21ES011666R21HD0664712R01HD041702101-2314-B-400-009-MY2103-2314-B-400-004-MY32016YFC02065079164320121477087NICHD R24HD04285
Variants in the fetal genome near pro-inflammatory cytokine genes on 2q13 associate with gestational duration
The duration of pregnancy is influenced by fetal and maternal genetic and non-genetic factors. Here we report a fetal genome-wide association meta-analysis of gestational duration, and early preterm, preterm, and postterm birth in 84,689 infants. One locus on chromosome 2q13 is associated with gestational duration; the association is replicated in 9,291 additional infants (combined P= 3.96 x 10(-14)). Analysis of 15,588 mother-child pairs shows that the association is driven by fetal rather than maternal genotype. Functional experiments show that the lead SNP, rs7594852, alters the binding of the HIC1 transcriptional repressor. Genes at the locus include several interleukin 1 family members with roles in pro-inflammatory pathways that are central to the process of parturition. Further understanding of the underlying mechanisms will be of great public health importance, since giving birth either before or after the window of term gestation is associated with increased morbidity and mortality.Peer reviewe
Maternal and fetal genetic effects on birth weight and their relevance to cardio-metabolic risk factors.
Birth weight variation is influenced by fetal and maternal genetic and non-genetic factors, and has been reproducibly associated with future cardio-metabolic health outcomes. In expanded genome-wide association analyses of own birth weight (n = 321,223) and offspring birth weight (n = 230,069 mothers), we identified 190 independent association signals (129 of which are novel). We used structural equation modeling to decompose the contributions of direct fetal and indirect maternal genetic effects, then applied Mendelian randomization to illuminate causal pathways. For example, both indirect maternal and direct fetal genetic effects drive the observational relationship between lower birth weight and higher later blood pressure: maternal blood pressure-raising alleles reduce offspring birth weight, but only direct fetal effects of these alleles, once inherited, increase later offspring blood pressure. Using maternal birth weight-lowering genotypes to proxy for an adverse intrauterine environment provided no evidence that it causally raises offspring blood pressure, indicating that the inverse birth weight-blood pressure association is attributable to genetic effects, and not to intrauterine programming.The Fenland Study is funded by the Medical Research Council (MC_U106179471) and
Wellcome Trust
Variants in the fetal genome near pro-inflammatory cytokine genes on 2q13 associate with gestational duration
The duration of pregnancy is influenced by fetal and maternal genetic and non-genetic factors. Here we report a fetal genome-wide association meta-analysis of gestational duration, and early preterm, preterm, and postterm birth in 84,689 infants. One locus on chromosome 2q13 is associated with gestational duration; the association is replicated in 9,291 additional infants (combined P= 3.96 x 10(-14)). Analysis of 15,588 mother-child pairs shows that the association is driven by fetal rather than maternal genotype. Functional experiments show that the lead SNP, rs7594852, alters the binding of the HIC1 transcriptional repressor. Genes at the locus include several interleukin 1 family members with roles in pro-inflammatory pathways that are central to the process of parturition. Further understanding of the underlying mechanisms will be of great public health importance, since giving birth either before or after the window of term gestation is associated with increased morbidity and mortality
Whole-transcriptome analysis delineates the human placenta gene network and its associations with fetal growth
Abstract Background The placenta is the principal organ regulating intrauterine growth and development, performing critical functions on behalf of the developing fetus. The delineation of functional networks and pathways driving placental processes has the potential to provide key insight into intrauterine perturbations that result in adverse birth as well as later life health outcomes. Results We generated the transcriptome-wide profile of 200 term human placenta using the Illumina HiSeq 2500 platform and characterized the functional placental gene network using weighted gene coexpression network analysis (WGCNA). We identified 17 placental coexpression network modules that were dominated by functional processes including growth, organ development, gas exchange and immune response. Five network modules, enriched for processes including cellular respiration, amino acid transport, hormone signaling, histone modifications and gene expression, were associated with birth weight; hub genes of all five modules (CREB3, DDX3X, DNAJC14, GRHL1 and C21orf91) were significantly associated with fetal growth restriction, and one hub gene (CREB3) was additionally associated with fetal overgrowth. Conclusions In this largest RNA-Seq based transcriptome-wide profiling study of human term placenta conducted to date, we delineated a placental gene network with functional relevance to fetal growth using a network-based approach with superior scale reduction capacity. Our study findings not only implicate potential molecular mechanisms underlying fetal growth but also provide a reference placenta gene network to inform future studies investigating placental dysfunction as a route to future disease endpoints
Additional file 5: of Whole-transcriptome analysis delineates the human placenta gene network and its associations with fetal growth
Mapping of GWAS-linked genes in placental gene coexpression network. Genes linked to GWAS-associated traits that are enriched in the placental gene coexpression network are listed alongside assigned modules and GWAS-linked traits. (CSV 58Â kb