Publications
74 results found
McArdle AJ, Webbe J, Sim K, et al., 2016, Determinants of Carboxyhemoglobin Levels and Relationship with Sepsis in a Retrospective Cohort of Preterm Neonates, PLOS One, Vol: 11, ISSN: 1932-6203
Carboxyhemoglobin levels in blood reflect endogenous carbon monoxide production and are often measured during routine blood gas analysis. Endogenous carbon monoxide production has been reported to be increased during sepsis, but carboxyhemoglobin levels have not been thoroughly evaluated as a biomarker of sepsis. We sought to determine whether carboxyhemoglobin levels were elevated during sepsis in a high risk population of premature neonates. We conducted a retrospective cohort study of 30 infants in two neonatal intensive care units using electronic medical and laboratory records. The majority of infants were extremely premature and extremely low birth weight, and 25 had at least one episode of sepsis. We collected all carboxyhemoglobin measurements during their in-patient stay and examined the relationship between carboxyhemoglobin and a variety of clinical and laboratory parameters, in addition to the presence or absence of sepsis, using linear mixed-effect models. We found that postnatal age had the most significant effect on carboxyhemoglobin levels, and other significant associations were identified with gestational age, hemoglobin concentration, oxyhemoglobin saturation, and blood pH. Accounting for these covariates, there was no significant relationship between the onset of sepsis and carboxyhemoglobin levels. Our results show that carboxyhemoglobin is unlikely to be a clinically useful biomarker of sepsis in premature infants, and raise a note of caution about factors which may confound the use of carbon monoxide as a clinical biomarker for other disease processes such as hemolysis.
Davies S, Sutton N, Blackstock S, et al., 2015, Predicting IVIG resistance in UK Kawasaki disease, ARCHIVES OF DISEASE IN CHILDHOOD, Vol: 100, Pages: 366-368, ISSN: 0003-9888
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- Citations: 85
Hoggart CJ, Venturini G, Mangino M, et al., 2014, Novel Approach Identifies SNPs in SLC2A10 and KCNK9 with Evidence for Parent-of-Origin Effect on Body Mass Index, PLOS Genetics, Vol: 10, ISSN: 1553-7390
The phenotypic effect of some single nucleotide polymorphisms (SNPs) depends on their parental origin. We present anovel approach to detect parent-of-origin effects (POEs) in genome-wide genotype data of unrelated individuals. Themethod exploits increased phenotypic variance in the heterozygous genotype group relative to the homozygous groups.We applied the method to .56,000 unrelated individuals to search for POEs influencing body mass index (BMI). Six leadSNPs were carried forward for replication in five family-based studies (of ,4,000 trios). Two SNPs replicated: the paternalrs2471083-C allele (located near the imprinted KCNK9 gene) and the paternal rs3091869-T allele (located near the SLC2A10gene) increased BMI equally (beta = 0.11 (SD), P,0.0027) compared to the respective maternal alleles. Real-time PCRexperiments of lymphoblastoid cell lines from the CEPH families showed that expression of both genes was dependent onparental origin of the SNPs alleles (P,0.01). Our scheme opens new opportunities to exploit GWAS data of unrelatedindividuals to identify POEs and demonstrates that they play an important role in adult obesity.
Speed D, Hoggart C, Petrovski S, et al., 2014, Genome-wide association study and biological pathway analysis of epilepsy prognosis in a prospective cohort of newly treated epilepsy, Human Molecular Genetics
Fatemifar G, Hoggart CJ, Paternoster L, et al., 2013, Genome-wide association study of primary tooth eruption identifies pleiotropic loci associated with height and craniofacial distances, HUMAN MOLECULAR GENETICS, Vol: 22, Pages: 3807-3817, ISSN: 0964-6906
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- Citations: 61
al Basatena N-KS, Hoggart CJ, Coin LJ, et al., 2013, The Effect of Genomic Inversions on Estimation of Population Genetic Parameters from SNP Data, GENETICS, Vol: 193, Pages: 243-253, ISSN: 0016-6731
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- Citations: 10
O'Reilly P, Hoggart C, 2013, A Novel Method to Prioritise Genetic Loci Identified in GWAS for Sequencing, 42nd European Mathematical Genetics Meeting (EMGM), Publisher: KARGER, Pages: 111-111, ISSN: 0001-5652
Ehret GB, Lamparter D, Hoggart CJ, et al., 2012, A Multi-SNP Locus-Association Method Reveals a Substantial Fraction of the Missing Heritability, AMERICAN JOURNAL OF HUMAN GENETICS, Vol: 91, Pages: 863-871, ISSN: 0002-9297
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- Citations: 34
Papathomas M, Molitor J, Hoggart C, et al., 2012, Exploring Data From Genetic Association Studies Using Bayesian Variable Selection and the Dirichlet Process: Application to Searching for Gene Gene Patterns, GENETIC EPIDEMIOLOGY, Vol: 36, Pages: 663-674, ISSN: 0741-0395
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- Citations: 30
Fatemifar G, Hoggart C, Prokopenko I, et al., 2012, GENOME-WIDE ASSOCIATION STUDY OF PRIMARY TOOTH ERUPTION, Osteoporosis and Bone Conference, Publisher: SPRINGER LONDON LTD, Pages: S562-S562, ISSN: 0937-941X
Hoggart C, Brennan P, Tjonneland A, et al., 2012, A Risk Model for Lung Cancer Incidence, CANCER PREVENTION RESEARCH, Vol: 5, Pages: 834-846, ISSN: 1940-6207
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- Citations: 79
O'Reilly PF, Hoggart CJ, Pomyen Y, et al., 2012, MultiPhen: Joint Model of Multiple Phenotypes Can Increase Discovery in GWAS, PLOS One, Vol: 7, ISSN: 1932-6203
The genome-wide association study (GWAS) approach has discovered hundreds of genetic variants associated with diseasesand quantitative traits. However, despite clinical overlap and statistical correlation between many phenotypes, GWAS aregenerally performed one-phenotype-at-a-time. Here we compare the performance of modelling multiple phenotypes jointlywith that of the standard univariate approach. We introduce a new method and software, MultiPhen, that models multiplephenotypes simultaneously in a fast and interpretable way. By performing ordinal regression, MultiPhen tests the linearcombination of phenotypes most associated with the genotypes at each SNP, and thus potentially captures effects hiddento single phenotype GWAS. We demonstrate via simulation that this approach provides a dramatic increase in power inmany scenarios. There is a boost in power for variants that affect multiple phenotypes and for those that affect only onephenotype. While other multivariate methods have similar power gains, we describe several benefits of MultiPhen overthese. In particular, we demonstrate that other multivariate methods that assume the genotypes are normally distributed,such as canonical correlation analysis (CCA) and MANOVA, can have highly inflated type-1 error rates when testing casecontrolor non-normal continuous phenotypes, while MultiPhen produces no such inflation. To test the performance ofMultiPhen on real data we applied it to lipid traits in the Northern Finland Birth Cohort 1966 (NFBC1966). In these dataMultiPhen discovers 21% more independent SNPs with known associations than the standard univariate GWAS approach,while applying MultiPhen in addition to the standard approach provides 37% increased discovery. The most associatedlinear combinations of the lipids estimated by MultiPhen at the leading SNPs accurately reflect the Friedewald Formula,suggesting that MultiPhen could be used to refine the definition of existing phenotypes or uncover novel heritablepheno
Fatemifar G, Hoggart C, Prokopenko I, et al., 2012, Genome-wide association study of primary tooth eruption, 39th Annual Congress of the European-Calcified-Tissue-Society (ECTS), Publisher: ELSEVIER SCIENCE INC, Pages: S107-S107, ISSN: 8756-3282
Hoggart CJ, O'Reilly PF, Kaakinen M, et al., 2012, Fine-Scale Estimation of Location of Birth from Genome-Wide Single-Nucleotide Polymorphism Data, GENETICS, Vol: 190, Pages: 669-U583, ISSN: 0016-6731
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- Citations: 7
Salvi E, Kutalik Z, Glorioso N, et al., 2012, Genomewide Association Study Using a High-Density Single Nucleotide Polymorphism Array and Case-Control Design Identifies a Novel Essential Hypertension Susceptibility Locus in the Promoter Region of Endothelial NO Synthase, HYPERTENSION, Vol: 59, Pages: 248-+, ISSN: 0194-911X
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- Citations: 120
Warren HR, Casas J-P, Hoggart C, et al., 2012, Comparisons Of Shrinkage Estimation Methods For Improved Prediction Of Quantitative Phenotypic Traits Related To Individual CVD Risk, 20th Annual Meeting of the International-Genetic-Epidemiology-Society (IGES), Publisher: WILEY-BLACKWELL, Pages: 151-151, ISSN: 0741-0395
Ma J, Xiao F, Xiong M, et al., 2012, Natural and Orthogonal Interaction Framework for Modeling Gene-Environment Interactions with Application to Lung Cancer, HUMAN HEREDITY, Vol: 73, Pages: 185-194, ISSN: 0001-5652
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- Citations: 9
Eleftherohorinou H, Hoggart CJ, Wright VJ, et al., 2011, Pathway-driven gene stability selection of two rheumatoid arthritis GWAS identifies and validates new susceptibility genes in receptor mediated signalling pathways, Human Molecular Genetics, Vol: 20, Pages: 3494-3506
Ducci F, Kaakinen M, Pouta A, et al., 2011, <i>TTC12</i>-<i>ANKK1</i>-<i>DRD2</i> and <i>CHRNA5</i>-<i>CHRNA3</i>-<i>CHRNB4</i> Influence Different Pathways Leading to Smoking Behavior from Adolescence to Mid-Adulthood, BIOLOGICAL PSYCHIATRY, Vol: 69, Pages: 650-660, ISSN: 0006-3223
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- Citations: 58
O'Reilly PF, Coin LJM, Hoggart CJ, 2010, invertFREGENE: software for simulating inversions in population genetic data, BIOINFORMATICS, Vol: 26, Pages: 838-840, ISSN: 1367-4803
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- Citations: 10
Pillas D, Hoggart CJ, Evans DM, et al., 2010, Genome-Wide Association Study Reveals Multiple Loci Associated with Primary Tooth Development during Infancy, PLOS Genetics, Vol: 6, ISSN: 1553-7390
Tooth development is a highly heritable process which relates to other growth and developmental processes, and which interacts with the development of the entire craniofacial complex. Abnormalities of tooth development are common, with tooth agenesis being the most common developmental anomaly in humans. We performed a genome-wide association study of time to first tooth eruption and number of teeth at one year in 4,564 individuals from the 1966 Northern Finland Birth Cohort (NFBC1966) and 1,518 individuals from the Avon Longitudinal Study of Parents and Children (ALSPAC). We identified 5 loci at P<5×10−8, and 5 with suggestive association (P<5×10−6). The loci included several genes with links to tooth and other organ development (KCNJ2, EDA, HOXB2, RAD51L1, IGF2BP1, HMGA2, MSRB3). Genes at four of the identified loci are implicated in the development of cancer. A variant within the HOXB gene cluster associated with occlusion defects requiring orthodontic treatment by age 31 years.
Pillas D, Hoggart CJ, Evans DM, et al., 2010, Correction: Genome-Wide Association Study Reveals Multiple Loci Associated with Primary Tooth Development during Infancy., PLoS Genet, Vol: 6, ISSN: 1553-7404
[This corrects the article on p. e1000856 in vol. 6.].
Chambers JC, Zhang W, Li Y, et al., 2009, Genome-wide association study identifies variants in <i>TMPRSS6</i> associated with hemoglobin levels, NATURE GENETICS, Vol: 41, Pages: 1170-1172, ISSN: 1061-4036
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- Citations: 188
Eleftherohorinou H, Wright V, Hoggart C, et al., 2009, Analysis of GWAS provides new insights into genetic susceptibility to 3 inflammatory diseases, PLoS One, Vol: 4, Pages: 1-11, ISSN: 1932-6203
Although the introduction of genome-wide association studies (GWAS) have greatly increased the number of genes associated with common diseases, only a small proportion of the predicted genetic contribution has so far been elucidated. Studying the cumulative variation of polymorphisms in multiple genes acting in functional pathways may provide a complementary approach to the more common single SNP association approach in understanding genetic determinants of common disease. We developed a novel pathway-based method to assess the combined contribution of multiple genetic variants acting within canonical biological pathways and applied it to data from 14,000 UK individuals with 7 common diseases. We tested inflammatory pathways for association with Crohn's disease (CD), rheumatoid arthritis (RA) and type 1 diabetes (T1D) with 4 non-inflammatory diseases as controls. Using a variable selection algorithm, we identified variants responsible for the pathway association and evaluated their use for disease prediction using a 10 fold cross-validation framework in order to calculate out-of-sample area under the Receiver Operating Curve (AUC). The generalisability of these predictive models was tested on an independent birth cohort from Northern Finland. Multiple canonical inflammatory pathways showed highly significant associations (p 10−3–10−20) with CD, T1D and RA. Variable selection identified on average a set of 205 SNPs (149 genes) for T1D, 350 SNPs (189 genes) for RA and 493 SNPs (277 genes) for CD. The pattern of polymorphisms at these SNPS were found to be highly predictive of T1D (91% AUC) and RA (85% AUC), and weakly predictive of CD (60% AUC). The predictive ability of the T1D model (without any parameter refitting) had good predictive ability (79% AUC) in the Finnish cohort. Our analysis suggests that genetic contribution to common inflammatory diseases operates through multiple genes interacting in functional pathways.
Sovio U, Bennett AJ, Millwood IY, et al., 2009, Genetic Determinants of Height Growth Assessed Longitudinally from Infancy to Adulthood in the Northern Finland Birth Cohort 1966, PLOS Genetics, Vol: 5, ISSN: 1553-7390
Recent genome-wide association (GWA) studies have identified dozens of common variants associated with adult height. However, it is unknown how these variants influence height growth during childhood. We derived peak height velocity in infancy (PHV1) and puberty (PHV2) and timing of pubertal height growth spurt from parametric growth curves fitted to longitudinal height growth data to test their association with known height variants. The study consisted of N = 3,538 singletons from the prospective Northern Finland Birth Cohort 1966 with genotype data and frequent height measurements (on average 20 measurements per person) from 0–20 years. Twenty-six of the 48 variants tested associated with adult height (p<0.05, adjusted for sex and principal components) in this sample, all in the same direction as in previous GWA scans. Seven SNPs in or near the genes HHIP, DLEU7, UQCC, SF3B4/SV2A, LCORL, and HIST1H1D associated with PHV1 and five SNPs in or near SOCS2, SF3B4/SV2A, C17orf67, CABLES1, and DOT1L with PHV2 (p<0.05). We formally tested variants for interaction with age (infancy versus puberty) and found biologically meaningful evidence for an age-dependent effect for the SNP in SOCS2 (p = 0.0030) and for the SNP in HHIP (p = 0.045). We did not have similar prior evidence for the association between height variants and timing of pubertal height growth spurt as we had for PHVs, and none of the associations were statistically significant after correction for multiple testing. The fact that in this sample, less than half of the variants associated with adult height had a measurable effect on PHV1 or PHV2 is likely to reflect limited power to detect these associations in this dataset. Our study is the first genetic association analysis on longitudinal height growth in a prospective cohort from birth to adulthood and gives grounding for future research on the genetic regulation of human height during different periods of growth.
Sabatti C, Service SK, Hartikainen A-L, et al., 2009, Genome-wide association analysis of metabolic traits in a birth cohort from a founder population, NATURE GENETICS, Vol: 41, Pages: 35-46, ISSN: 1061-4036
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- Citations: 575
Chadeau-Hyam M, Hoggart CJ, O'Reilly PF, et al., 2008, Fregene: Simulation of realistic sequence-level data in populations and ascertained samples, BMC BIOINFORMATICS, Vol: 9, ISSN: 1471-2105
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- Citations: 48
Hoggart CJ, Whittaker JC, De Iorio M, et al., 2008, Simultaneous Analysis of All SNPs in Genome-Wide and Re-Sequencing Association Studies, PLOS GENETICS, Vol: 4, ISSN: 1553-7404
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- Citations: 242
Hoggart CJ, Clark TG, De Lorio M, et al., 2008, Genome-wide significance for dense SNP and resequencing data, GENETIC EPIDEMIOLOGY, Vol: 32, Pages: 179-185, ISSN: 0741-0395
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- Citations: 157
Hoggart CJ, Chadeau-Hyam M, Clark TG, et al., 2007, Sequence-level population simulations over large genomic regions, GENETICS, Vol: 177, Pages: 1725-1731, ISSN: 0016-6731
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- Citations: 79
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