Author
Haja N. Kadarmideen
Other affiliations: ETH Zurich, Commonwealth Scientific and Industrial Research Organisation, École Polytechnique Fédérale de Lausanne ...read more
Bio: Haja N. Kadarmideen is an academic researcher from Technical University of Denmark. The author has contributed to research in topics: Population & Residual feed intake. The author has an hindex of 31, co-authored 150 publications receiving 3842 citations. Previous affiliations of Haja N. Kadarmideen include ETH Zurich & Commonwealth Scientific and Industrial Research Organisation.
Papers published on a yearly basis
Papers
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Momoko Horikoshi1, Robin N Beaumont2, Felix R. Day3, Nicole M. Warrington4 +182 more•Institutions (55)
TL;DR: In this paper, the authors performed a meta-analysis of birth weight in 153,781 individuals, identifying 60 loci where fetal genotype was associated with birth weight (P < 5.5×10−8).
Abstract: Birth weight (BW) has been shown to be influenced by both fetal and maternal factors and in observational studies is reproducibly associated with future risk of adult metabolic diseases including type 2 diabetes (T2D) and cardiovascular disease1. These life-course associations have often been attributed to the impact of an adverse early life environment. Here, we performed a multi-ancestry genome-wide association study (GWAS) meta-analysis of BW in 153,781 individuals, identifying 60 loci where fetal genotype was associated with BW (P < 5 × 10−8). Overall, approximately 15% of variance in BW was captured by assays of fetal genetic variation. Using genetic association alone, we found strong inverse genetic correlations between BW and systolic blood pressure (Rg = −0.22, P = 5.5 × 10−13), T2D (Rg = −0.27, P = 1.1 × 10−6) and coronary artery disease (Rg = −0.30, P = 6.5 × 10−9). In addition, using large -cohort datasets, we demonstrated that genetic factors were the major contributor to the negative covariance between BW and future cardiometabolic risk. Pathway analyses indicated that the protein products of genes within BW-associated regions were enriched for diverse processes including insulin signalling, glucose homeostasis, glycogen biosynthesis and chromatin remodelling. There was also enrichment of associations with BW in known imprinted regions (P = 1.9 × 10−4). We demonstrate that life-course associations between early growth phenotypes and adult cardiometabolic disease are in part the result of shared genetic effects and identify some of the pathways through which these causal genetic effects are mediated.
370 citations
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Nicole M. Warrington1, Robin N Beaumont2, Momoko Horikoshi3, Felix R. Day4 +242 more•Institutions (79)
TL;DR: An expanded GWAS of birth weight and subsequent analysis using structural equation modeling and Mendelian randomization decomposes maternal and fetal genetic contributions and causal links between birth weight, blood pressure and glycemic traits.
Abstract: 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.
323 citations
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Erasmus University Rotterdam1, University of Pennsylvania2, University of Bristol3, Statens Serum Institut4, Ludwig Maximilian University of Munich5, University of Copenhagen6, University of Oxford7, University of Turku8, University of Eastern Finland9, University College London10, Queen Mary University of London11, University of Oulu12, Imperial College London13, VU University Amsterdam14, University of Helsinki15, University of Western Australia16, University Hospital of South Manchester NHS Foundation Trust17, Novo Nordisk18, Norwegian Institute of Public Health19, Pompeu Fabra University20, Harokopio University21, University of Leicester22, National Institute for Health and Welfare23, University of Groningen24, Leipzig University25, University of Warwick26, Broad Institute27, Harvard University28, Shanghai Jiao Tong University29, Dalian Maritime University30, University of Manchester31, University of Gothenburg32, Wellcome Trust Sanger Institute33, Hammersmith Hospital34, Medical Research Council35, University of South Australia36, Churchill Hospital37, Stanford University38, Cincinnati Children's Hospital Medical Center39, Creighton University40, University of Southern California41, Columbia University42
TL;DR: A meta-analysis of genome-wide association studies of childhood body mass index, using sex- and age-adjusted standard deviation scores, identifies three novel loci that likely represent age-related differences in strength of the associations with bodymass index.
Abstract: A large number of genetic loci are associated with adult body mass index. However, the genetics of childhood body mass index are largely unknown. We performed a meta-analysis of genome-wide association studies of childhood body mass index, using sex- and age-adjusted standard deviation scores. We included 35 668 children from 20 studies in the discovery phase and 11 873 children from 13 studies in the replication phase. In total, 15 loci reached genome-wide significance (P-value < 5 × 10(-8)) in the joint discovery and replication analysis, of which 12 are previously identified loci in or close to ADCY3, GNPDA2, TMEM18, SEC16B, FAIM2, FTO, TFAP2B, TNNI3K, MC4R, GPR61, LMX1B and OLFM4 associated with adult body mass index or childhood obesity. We identified three novel loci: rs13253111 near ELP3, rs8092503 near RAB27B and rs13387838 near ADAM23. Per additional risk allele, body mass index increased 0.04 Standard Deviation Score (SDS) [Standard Error (SE) 0.007], 0.05 SDS (SE 0.008) and 0.14 SDS (SE 0.025), for rs13253111, rs8092503 and rs13387838, respectively. A genetic risk score combining all 15 SNPs showed that each additional average risk allele was associated with a 0.073 SDS (SE 0.011, P-value = 3.12 × 10(-10)) increase in childhood body mass index in a population of 1955 children. This risk score explained 2% of the variance in childhood body mass index. This study highlights the shared genetic background between childhood and adult body mass index and adds three novel loci. These loci likely represent age-related differences in strength of the associations with body mass index.
247 citations
01 Jan 2016
244 citations
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TL;DR: Results show that future selection programmes should include disease and fertility for genetic improvement of health and reproduction and for sustained economic growth in the dairy cattle industry.
Abstract: This study provides estimates of genetic parameters for various diseases, fertility and 305-day milk production traits in dairy cattle using data from a UK national milk recording scheme. The data set consisted of 63891 multiple lactation records on diseases (mastitis, lameness, milk fever, ketosis and tetany), fertility traits (calving interval, conception to first service, number of services for a conception, and number of days to first service), dystocia and 305-day milk, fat and protein yield. All traits were analysed by multi-trait repeatability linear animal models (LM). Binary diseases and fertility traits were further analysed by threshold sire models (TM). Both LM and TM analyses were based on the generalized linear mixed model framework. The LM included herd-year-season of calving (HYS), age at calving and parity as fixed effects and genetic, permanent environmental and residual effects as random. The TM analyses included the same effects as for LM, but HYS effects were treated as random to avoid convergence problems when HYS sub-classes had 0 or 100% incidence. Because HYS effects were treated as random, herd effects were fitted as fixed effects to account for effect of herds in the data. The LM estimates of heritability ranged from 0•389 to 0•399 for 305-day milk production traits, 0•010 to 0•029 for fertility traits and 0•004 to 0•038 for diseases. The LM estimates of repeatability ranged from 0•556 to 0•586 for 305-day milk production traits, 0•029 to 0•086 for fertility traits and 0•004 to 0•100 for diseases. The TM estimates of heritabilities and repeatabilities were greater than LM estimates for binary traits and were in the range 0•012 to 0•126 and 0•013 to 0•168, respectively. Genetic correlations between milk production traits and fertility and diseases were all unfavorable: they ranged from 0•07 to 0•37 for milk production and diseases, 0•31 to 0•54 for milk production and poor fertility and 0•06 to 0•41 for diseases and poor fertility. These results show that future selection programmes should include disease and fertility for genetic improvement of health and reproduction and for sustained economic growth in the dairy cattle industry.
219 citations
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TL;DR: For the next few weeks the course is going to be exploring a field that’s actually older than classical population genetics, although the approach it’ll be taking to it involves the use of population genetic machinery.
Abstract: So far in this course we have dealt entirely with the evolution of characters that are controlled by simple Mendelian inheritance at a single locus. There are notes on the course website about gametic disequilibrium and how allele frequencies change at two loci simultaneously, but we didn’t discuss them. In every example we’ve considered we’ve imagined that we could understand something about evolution by examining the evolution of a single gene. That’s the domain of classical population genetics. For the next few weeks we’re going to be exploring a field that’s actually older than classical population genetics, although the approach we’ll be taking to it involves the use of population genetic machinery. If you know a little about the history of evolutionary biology, you may know that after the rediscovery of Mendel’s work in 1900 there was a heated debate between the “biometricians” (e.g., Galton and Pearson) and the “Mendelians” (e.g., de Vries, Correns, Bateson, and Morgan). Biometricians asserted that the really important variation in evolution didn’t follow Mendelian rules. Height, weight, skin color, and similar traits seemed to
9,847 citations
01 Jan 2016
TL;DR: The modern applied statistics with s is universally compatible with any devices to read, and is available in the digital library an online access to it is set as public so you can download it instantly.
Abstract: Thank you very much for downloading modern applied statistics with s. As you may know, people have search hundreds times for their favorite readings like this modern applied statistics with s, but end up in harmful downloads. Rather than reading a good book with a cup of coffee in the afternoon, instead they cope with some harmful virus inside their laptop. modern applied statistics with s is available in our digital library an online access to it is set as public so you can download it instantly. Our digital library saves in multiple countries, allowing you to get the most less latency time to download any of our books like this one. Kindly say, the modern applied statistics with s is universally compatible with any devices to read.
5,249 citations
01 Aug 2000
TL;DR: Assessment of medical technology in the context of commercialization with Bioentrepreneur course, which addresses many issues unique to biomedical products.
Abstract: BIOE 402. Medical Technology Assessment. 2 or 3 hours. Bioentrepreneur course. Assessment of medical technology in the context of commercialization. Objectives, competition, market share, funding, pricing, manufacturing, growth, and intellectual property; many issues unique to biomedical products. Course Information: 2 undergraduate hours. 3 graduate hours. Prerequisite(s): Junior standing or above and consent of the instructor.
4,833 citations
01 Jan 2000
3,536 citations
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TL;DR: It is found that local genetic variation affects gene expression levels for the majority of genes, and inter-chromosomal genetic effects for 93 genes and 112 loci are identified, enabling a mechanistic interpretation of gene regulation and the genetic basis of disease.
Abstract: Characterization of the molecular function of the human genome and its variation across individuals is essential for identifying the cellular mechanisms that underlie human genetic traits and diseases. The Genotype-Tissue Expression (GTEx) project aims to characterize variation in gene expression levels across individuals and diverse tissues of the human body, many of which are not easily accessible. Here we describe genetic effects on gene expression levels across 44 human tissues. We find that local genetic variation affects gene expression levels for the majority of genes, and we further identify inter-chromosomal genetic effects for 93 genes and 112 loci. On the basis of the identified genetic effects, we characterize patterns of tissue specificity, compare local and distal effects, and evaluate the functional properties of the genetic effects. We also demonstrate that multi-tissue, multi-individual data can be used to identify genes and pathways affected by human disease-associated variation, enabling a mechanistic interpretation of gene regulation and the genetic basis of disease.
3,289 citations