Imperial College London

Dr Toby Andrew

Faculty of MedicineDepartment of Medicine

Lecturer in Human Genomics
 
 
 
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Contact

 

+44 (0)20 7594 6511t.andrew

 
 
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Location

 

E305Burlington DanesHammersmith Campus

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Summary

 

Publications

Publication Type
Year
to

84 results found

Andrew T, Genome-wide linkage scans and basic bioinformatics implemented using Stata/SE

Searches for genes using linkage analyses with genetic markers placed acrossthe entire human genome are hypothesis-free experiments, which represent anextreme form of multiple testing. As such, the low p-values required to obtainnominal significance make accurate diagnostics essential to assess model fitand to eliminate naive incorrect results. In hypothesis-driven single tests,researchers usually take good care to assess model fit and the validity ofmodel assumptions, but such concerns are usually ignored when it comes tolinkage analysis. This is particularly problematic where low thresholds (p > 0.0001)can result in extreme sensitivity to outlying observations and for somemodels (e.g. standard variance component analysis), greater sensitivity toviolation of model assumptions.Here we attempt to address these problems for genomic data based on 1300healthy sib-pairs (dizygotic twins) using modified Haseman-Elstonregression-based linkage analysis for quantitative traits, in which sib-pairphenotypic covariance is correlated with genetic marker covariance. Thestatistical theory underpinning the implementation of tests for linkage usinggeneralized linear models (GLM) (Author-Email: glm in Stata) is documented in detail elsewhere. In brief, the advantage ofanalysing sib-pairs using GLM is that the approach shares all of the strengthsof OLS and variance components, but none of their weaknesses. These are that(1) unlike OLS, the residual errors are correctly specified with a gammadistribution and known heteroscedasticity is accounted for; (2) unlike standardvariance components, by freely estimating the coefficient of variation, GLM is robust tophenotypic deviations from multivariate normality.Just as important are the practical advantages. With the release ofStata8/Special Edition for large datasets, we have been able to store and checkgenetic markers for all 22 pairs of autosomal chromosomes plus sex chromosomes. In addition, we have generated 2-pointand multipoint al

SCHOLARLY EDITION

Lau W, Andrew T, Maniatis N, 2017, High-Resolution Genetic Maps Identify Multiple Type 2 Diabetes Loci at Regulatory Hotspots in African Americans and Europeans, AMERICAN JOURNAL OF HUMAN GENETICS, Vol: 100, Pages: 803-816, ISSN: 0002-9297

JOURNAL ARTICLE

Ahmadi KR, Andrew T, 2014, Opportunism: a panacea for implementation of whole-genome sequencing studies in nutrigenomics research?, GENES AND NUTRITION, Vol: 9, ISSN: 1555-8932

JOURNAL ARTICLE

Direk K, Lau W, Small KS, Maniatis N, Andrew Tet al., 2014, ABCC5 Transporter is a Novel Type 2 Diabetes Susceptibility Gene in European and African American Populations, ANNALS OF HUMAN GENETICS, Vol: 78, Pages: 333-344, ISSN: 0003-4800

JOURNAL ARTICLE

Andrew T, Gill R, Gillham-Nasenya I, Ahmadi KRet al., 2013, Unravelling the basis of variability in cobalamin levels in the general population, BRITISH JOURNAL OF NUTRITION, Vol: 110, Pages: 1672-1679, ISSN: 0007-1145

JOURNAL ARTICLE

Direk K, Cecelja M, Astle W, Chowienczyk P, Spector TD, Falchi M, Andrew Tet al., 2013, The relationship between DXA-based and anthropometric measures of visceral fat and morbidity in women, BMC CARDIOVASCULAR DISORDERS, Vol: 13, ISSN: 1471-2261

JOURNAL ARTICLE

Lopes MC, Hysi PG, Verhoeven VJM, Macgregor S, Hewitt AW, Montgomery GW, Cumberland P, Vingerling JR, Young TL, van Duijn CM, Oostra B, Uitterlinden AG, Rahi JS, Mackey DA, Klaver CCW, Andrew T, Hammond CJet al., 2013, Identification of a Candidate Gene for Astigmatism, INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE, Vol: 54, Pages: 1260-1267, ISSN: 0146-0404

JOURNAL ARTICLE

Andrew T, Calloway CD, Stuart S, Lee SH, Gill R, Clement G, Chowienczyk P, Spector TD, Valdes AMet al., 2011, A Twin Study of Mitochondrial DNA Polymorphisms Shows that Heteroplasmy at Multiple Sites Is Associated with mtDNA Variant 16093 but Not with Zygosity, PLOS ONE, Vol: 6, ISSN: 1932-6203

JOURNAL ARTICLE

Cotlarciuc I, Andrew T, Dew T, Clement G, Gill R, Surdulescu G, Sherwood R, Ahmadi KRet al., 2011, The Basis of Differential Responses to Folic Acid Supplementation, JOURNAL OF NUTRIGENETICS AND NUTRIGENOMICS, Vol: 4, Pages: 99-109, ISSN: 1661-6499

JOURNAL ARTICLE

Fahy SJ, Sun C, Zhu G, Healey PR, Spector TD, Martin NG, Mitchell P, Wong TY, Mackey DA, Hammond CJ, Andrew Tet al., 2011, The Relationship between Retinal Arteriolar and Venular Calibers Is Genetically Mediated, and Each Is Associated with Risk of Cardiovascular Disease, INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE, Vol: 52, Pages: 975-981, ISSN: 0146-0404

JOURNAL ARTICLE

Leschziner GD, Coffey AJ, Andrew T, Gregorio SP, Dias-Neto E, Calafato M, Bentley DR, Kinton L, Sander JW, Johnson MRet al., 2011, Q8IYL2 is a candidate gene for the familial epilepsy syndrome of Partial Epilepsy with Pericentral Spikes (PEPS), EPILEPSY RESEARCH, Vol: 96, Pages: 109-115, ISSN: 0920-1211

JOURNAL ARTICLE

Carbonaro F, Andrew T, Mackey DA, Spector TD, Hammond CJet al., 2010, Comparison of three methods of intraocular pressure measurement and their relation to central corneal thickness, EYE, Vol: 24, Pages: 1165-1170, ISSN: 0950-222X

JOURNAL ARTICLE

Hysi PG, Young TL, Mackey DA, Andrew T, Fernandez-Medarde A, Solouki AM, Hewitt AW, Macgregor S, Vingerling JR, Li Y-J, Ikram MK, Fai LY, Sham PC, Manyes L, Porteros A, Lopes MC, Carbonaro F, Fahy SJ, Martin NG, van Duijn CM, Spector TD, Rahi JS, Santos E, Klaver CCW, Hammond CJet al., 2010, A genome-wide association study for myopia and refractive error identifies a susceptibility locus at 15q25, NATURE GENETICS, Vol: 42, Pages: 902-+, ISSN: 1061-4036

JOURNAL ARTICLE

Ikram MK, Sim X, Jensen RA, Cotch MF, Hewitt AW, Ikram MA, Wang JJ, Klein R, Klein BEK, Breteler MMB, Cheung N, Liew G, Mitchell P, Uitterlinden AG, Rivadeneira F, Hofman A, de Jong PTVM, van Duijn CM, Kao L, Cheng C-Y, Smith AV, Glazer NL, Lumley T, McKnight B, Psaty BM, Jonasson F, Eiriksdottir G, Aspelund T, Harris TB, Launer LJ, Taylor KD, Li X, Iyengar SK, Xi Q, Sivakumaran TA, Mackey DA, MacGregor S, Martin NG, Young TL, Bis JC, Wiggins KL, Heckbert SR, Hammond CJ, Andrew T, Fahy S, Attia J, Holliday EG, Scott RJ, Islam FMA, Rotter JI, McAuley AK, Boerwinkle E, Tai ES, Gudnason V, Siscovick DS, Vingerling JR, Wong TYet al., 2010, Correction: Four Novel Loci (19q13, 6q24, 12q24, and 5q14) Influence the Microcirculation In Vivo., PLoS genetics, Vol: 6, ISSN: 1553-7390

JOURNAL ARTICLE

Ikram MK, Xueling S, Jensen RA, Cotch MF, Hewitt AW, Ikram MA, Wang JJ, Klein R, Klein BEK, Breteler MMB, Cheung N, Liew G, Mitchell P, Uitterlinden AG, Rivadeneira F, Hofman A, de Jong PTVM, van Duijn CM, Kao L, Cheng C-Y, Smith AV, Glazer NL, Lumley T, McKnight B, Psaty BM, Jonasson F, Eiriksdottir G, Aspelund T, Harris TB, Launer LJ, Taylor KD, Li X, Iyengar SK, Xi Q, Sivakumaran TA, Mackey DA, MacGregor S, Martin NG, Young TL, Bis JC, Wiggins KL, Heckbert SR, Hammond CJ, Andrew T, Fahy S, Attia J, Holliday EG, Scott RJ, Islam FMA, Rotter JI, McAuley AK, Boerwinkle E, Tai ES, Gudnason V, Siscovick DS, Vingerling JR, Wong TYet al., 2010, Four Novel Loci (19q13, 6q24, 12q24, and 5q14) Influence the Microcirculation In Vivo, PLOS GENETICS, Vol: 6, ISSN: 1553-7390

JOURNAL ARTICLE

Macgregor S, Hewitt AW, Hysi PG, Ruddle JB, Medland SE, Henders AK, Gordon SD, Andrew T, McEvoy B, Sanfilippo PG, Carbonaro F, Tah V, Li YJ, Bennett SL, Craig JE, Montgomery GW, Tran-Viet K-N, Brown NL, Spector TD, Martin NG, Young TL, Hammond CJ, Mackey DAet al., 2010, Genome-wide association identifies ATOH7 as a major gene determining human optic disc size, HUMAN MOLECULAR GENETICS, Vol: 19, Pages: 2716-2724, ISSN: 0964-6906

JOURNAL ARTICLE

Nettleton JA, McKeown NM, Kanoni S, Lemaitre RN, Hivert M-F, Ngwa J, van Rooij FJA, Sonestedt E, Wojczynski MK, Ye Z, Tanaka T, Garcia M, Anderson JS, Follis JL, Djousse L, Mukamal K, Papoutsakis C, Mozaffarian D, Zillikens MC, Bandinelli S, Bennett AJ, Borecki IB, Feitosa MF, Ferrucci L, Forouhi NG, Groves CJ, Hallmans G, Harris T, Hofman A, Houston DK, Hu FB, Johansson I, Kritchevsky SB, Langenberg C, Launer L, Liu Y, Loos RJ, Nalls M, Orho-Melander M, Renstrom F, Rice K, Riserus U, Rolandsson O, Rotter JI, Saylor G, Sijbrands EJG, Sjogren P, Smith A, Steingrímsdóttir L, Uitterlinden AG, Wareham NJ, Prokopenko I, Pankow JS, van Duijn CM, Florez JC, Witteman JCM, MAGIC Investigators, Dupuis J, Dedoussis GV, Ordovas JM, Ingelsson E, Cupples LA, Siscovick DS, Franks PW, Meigs JBet al., 2010, Interactions of dietary whole-grain intake with fasting glucose- and insulin-related genetic loci in individuals of European descent: a meta-analysis of 14 cohort studies., Diabetes Care, Vol: 33, Pages: 2684-2691

OBJECTIVE: Whole-grain foods are touted for multiple health benefits, including enhancing insulin sensitivity and reducing type 2 diabetes risk. Recent genome-wide association studies (GWAS) have identified several single nucleotide polymorphisms (SNPs) associated with fasting glucose and insulin concentrations in individuals free of diabetes. We tested the hypothesis that whole-grain food intake and genetic variation interact to influence concentrations of fasting glucose and insulin. RESEARCH DESIGN AND METHODS: Via meta-analysis of data from 14 cohorts comprising ∼ 48,000 participants of European descent, we studied interactions of whole-grain intake with loci previously associated in GWAS with fasting glucose (16 loci) and/or insulin (2 loci) concentrations. For tests of interaction, we considered a P value <0.0028 (0.05 of 18 tests) as statistically significant. RESULTS: Greater whole-grain food intake was associated with lower fasting glucose and insulin concentrations independent of demographics, other dietary and lifestyle factors, and BMI (β [95% CI] per 1-serving-greater whole-grain intake: -0.009 mmol/l glucose [-0.013 to -0.005], P < 0.0001 and -0.011 pmol/l [ln] insulin [-0.015 to -0.007], P = 0.0003). No interactions met our multiple testing-adjusted statistical significance threshold. The strongest SNP interaction with whole-grain intake was rs780094 (GCKR) for fasting insulin (P = 0.006), where greater whole-grain intake was associated with a smaller reduction in fasting insulin concentrations in those with the insulin-raising allele. CONCLUSIONS: Our results support the favorable association of whole-grain intake with fasting glucose and insulin and suggest a potential interaction between variation in GCKR and whole-grain intake in influencing fasting insulin concentrations.

JOURNAL ARTICLE

Rakyan VK, Down TA, Maslau S, Andrew T, Yang T-P, Beyan H, Whittaker P, McCann OT, Finer S, Valdes AM, Leslie RD, Deloukas P, Spector TDet al., 2010, Human aging-associated DNA hypermethylation occurs preferentially at bivalent chromatin domains, GENOME RESEARCH, Vol: 20, Pages: 434-439, ISSN: 1088-9051

JOURNAL ARTICLE

Carbonaro F, Andrew T, Mackey DA, Young TL, Spector TD, Hammond CJet al., 2009, Repeated Measures of Intraocular Pressure Result in Higher Heritability and Greater Power in Genetic Linkage Studies, INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE, Vol: 50, Pages: 5115-5119, ISSN: 0146-0404

JOURNAL ARTICLE

Jun G, Guo H, Klein BEK, Klein R, Wang JJ, Mitchell P, Miao H, Lee KE, Joshi T, Buck M, Chugha P, Bardenstein D, Klein AP, Bailey-Wilson JE, Gong X, Spector TD, Andrew T, Hammond CJ, Elston RC, Iyengar SK, Wang Bet al., 2009, EPHA2 Is Associated with Age-Related Cortical Cataract in Mice and Humans, PLOS GENETICS, Vol: 5, ISSN: 1553-7390

JOURNAL ARTICLE

Kettunen J, Perola M, Martin NG, Cornes BK, Wilson SG, Montgomery GW, Benyamin B, Harris JR, Boomsma D, Willemsen G, Hottenga J-J, Slagboom PE, Christensen K, Kyvik KO, Sorensen TIA, Pedersen NL, Magnusson PKE, Andrew T, Spector TD, Widen E, Silventoinen K, Kaprio J, Palotie A, Peltonen Let al., 2009, Multicenter dizygotic twin cohort study confirms two linkage susceptibility loci for body mass index at 3q29 and 7q36 and identifies three further potential novel loci, INTERNATIONAL JOURNAL OF OBESITY, Vol: 33, Pages: 1235-1242, ISSN: 0307-0565

JOURNAL ARTICLE

Lopes MC, Andrew T, Carbonaro F, Spector TD, Hammond CJet al., 2009, Estimating Heritability and Shared Environmental Effects for Refractive Error in Twin and Family Studies, INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE, Vol: 50, Pages: 126-131, ISSN: 0146-0404

JOURNAL ARTICLE

Rahmioglu N, Andrew T, Cherkas L, Surdulescu G, Swaminathan R, Spector T, Ahmadi KRet al., 2009, Epidemiology and Genetic Epidemiology of the Liver Function Test Proteins, PLOS ONE, Vol: 4, ISSN: 1932-6203

JOURNAL ARTICLE

Zhai G, Andrew T, Kato BS, Blake GM, Spector TDet al., 2009, Genetic and environmental determinants on bone loss in postmenopausal Caucasian women: a 14-year longitudinal twin study, OSTEOPOROSIS INTERNATIONAL, Vol: 20, Pages: 949-953, ISSN: 0937-941X

JOURNAL ARTICLE

Andrew T, Maniatis N, Carbonaro F, Liew SHM, Lau W, Spector TD, Hammond CJet al., 2008, Identification and Replication of Three Novel Myopia Common Susceptibility Gene Loci on Chromosome 3q26 using Linkage and Linkage Disequilibrium Mapping, PLOS GENETICS, Vol: 4, ISSN: 1553-7390

JOURNAL ARTICLE

Carbonaro F, Andrew T, Mackey DA, Spector TD, Hammond CJet al., 2008, Heritability of intraocular pressure: a classical twin study, BRITISH JOURNAL OF OPHTHALMOLOGY, Vol: 92, Pages: 1125-1128, ISSN: 0007-1161

JOURNAL ARTICLE

Carbonaro F, Andrew T, Mackey DA, Spector TD, Hammond CJet al., 2008, The heritability of corneal hysteresis and ocular pulse amplitude - A twin study, OPHTHALMOLOGY, Vol: 115, Pages: 1545-1549, ISSN: 0161-6420

JOURNAL ARTICLE

Richards J, Rivadeneira F, Inouye M, Pastinen T, Soranzo N, Wilson SG, Andrew T, Falchi M, Gwilliam R, Ahmadi KR, Arp P, Valdes AM, Whittaker P, Verlaan DJ, Jhamai M, Kumanduri V, van Meurs JB, Hofman A, Pols HP, Hart D, Zhai G, Mullin BH, Deloukas P, Uitterlinden AG, Spector TDet al., 2008, Genome-Wide Association Study Reveals Genetic Variants Associated with Bone Mineral Density, Osteoporosis and Osteoporotic Fractures, 30th Annual Meeting of the American-Society-for-Bone-and-Mineral-Research, Publisher: AMER SOC BONE & MINERAL RES, Pages: S184-S184, ISSN: 0884-0431

CONFERENCE PAPER

Richards JB, Rivadeneira F, Inouye M, Pastinen TM, Soranzo N, Wilson SG, Andrew T, Falchi M, Gwilliam R, Ahmadi KR, Valdes AM, Arp P, Whittaker P, Verlaan DJ, Jhamai M, Kumanduri V, Moorhouse M, van Meurs JB, Hofman A, Pols HAP, Hart D, Zhai G, Kato BS, Mullin BH, Zhang F, Deloukas P, Uitterlinden AG, Spector TDet al., 2008, Bone mineral density, osteoporosis, and osteoporotic fractures: a genome-wide association study, LANCET, Vol: 371, Pages: 1505-1512, ISSN: 0140-6736

JOURNAL ARTICLE

Tachmazidou I, Andrew T, Verzilli CJ, Johnson MR, De Iorio Met al., 2008, Bayesian survival analysis in genetic association studies, BIOINFORMATICS, Vol: 24, Pages: 2030-2036, ISSN: 1367-4803

JOURNAL ARTICLE

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