Timothy M Frayling

Summary

Affiliation: Peninsula Medical School
Country: UK

Publications

  1. pmc A common variant of the p16(INK4a) genetic region is associated with physical function in older people
    David Melzer
    Peninsula Medical School, RD and E Wonford Site, Barrack Road, Exeter EX2 5DW, UK
    Mech Ageing Dev 128:370-7. 2007
  2. pmc Large-scale association analysis of TNF/LTA gene region polymorphisms in type 2 diabetes
    Vesna Boraska
    Department of Medical Biology, University of Split School of Medicine, Split, Croatia
    BMC Med Genet 11:69. 2010
  3. pmc The longitudinal association of common susceptibility variants for type 2 diabetes and obesity with fasting glucose level and BMI
    Rebecca J Webster
    Centre for Genetic Epidemiology and Biostatistics, University of Western Australia, Crawley, WA, Australia
    BMC Med Genet 11:140. 2010
  4. pmc FTO gene variation and measures of body mass in an African population
    Branwen J Hennig
    MRC International Nutrition Group, NPHIRU, EPH, London School of Hygiene and Tropical Medicine, London, UK
    BMC Med Genet 10:21. 2009
  5. pmc Triglyceride associated polymorphisms of the APOA5 gene have very different allele frequencies in Pune, India compared to Europeans
    Giriraj R Chandak
    Genome Research Group, Centre for Cellular and Molecular Biology, Hyderabad, India
    BMC Med Genet 7:76. 2006
  6. pmc Piecing together the FTO jigsaw
    Timothy M Frayling
    Peninsula College of Medicine and Dentistry, University of Exeter, Magdalen Road, Exeter EX1 2LU, UK
    Genome Biol 12:104. 2011
  7. ncbi request reprint A new era in finding Type 2 diabetes genes-the unusual suspects
    T M Frayling
    Peninsula Medical School, University of Exeter, Exeter, UK
    Diabet Med 24:696-701. 2007
  8. ncbi request reprint Genome-wide association studies provide new insights into type 2 diabetes aetiology
    Timothy M Frayling
    Genetics of Complex Traits, Institute of Biomedical and Clinical Sciences, Peninsula Medical School, University of Exeter, Exeter EX1 2LV, UK
    Nat Rev Genet 8:657-62. 2007
  9. pmc An interleukin-18 polymorphism is associated with reduced serum concentrations and better physical functioning in older people
    Timothy M Frayling
    Peninsula Medical School, Exeter, United Kingdom
    J Gerontol A Biol Sci Med Sci 62:73-8. 2007
  10. ncbi request reprint Commentary: Genetic association studies see light at the end of the tunnel
    Timothy M Frayling
    Genetics of Complex Traits, Peninsula Medical School, University of Exeter, EX1 2LU, UK
    Int J Epidemiol 37:133-5. 2008

Detail Information

Publications103 found, 100 shown here

  1. pmc A common variant of the p16(INK4a) genetic region is associated with physical function in older people
    David Melzer
    Peninsula Medical School, RD and E Wonford Site, Barrack Road, Exeter EX2 5DW, UK
    Mech Ageing Dev 128:370-7. 2007
    ..The mechanism involved may be via greater cellular restorative activity and reduced stem cell senescence...
  2. pmc Large-scale association analysis of TNF/LTA gene region polymorphisms in type 2 diabetes
    Vesna Boraska
    Department of Medical Biology, University of Split School of Medicine, Split, Croatia
    BMC Med Genet 11:69. 2010
    ..The purpose of this study is to examine T2D association of tag SNPs in the TNF/LTA region capturing the majority of common variation in a large-scale sample set of UK/Irish origin...
  3. pmc The longitudinal association of common susceptibility variants for type 2 diabetes and obesity with fasting glucose level and BMI
    Rebecca J Webster
    Centre for Genetic Epidemiology and Biostatistics, University of Western Australia, Crawley, WA, Australia
    BMC Med Genet 11:140. 2010
    ....
  4. pmc FTO gene variation and measures of body mass in an African population
    Branwen J Hennig
    MRC International Nutrition Group, NPHIRU, EPH, London School of Hygiene and Tropical Medicine, London, UK
    BMC Med Genet 10:21. 2009
    ..Variation in the fat mass and obesity associated (FTO) gene has been reproducibly associated with body mass index (BMI) and obesity in populations of White European origin. Data from Asians and African-Americans is less conclusive...
  5. pmc Triglyceride associated polymorphisms of the APOA5 gene have very different allele frequencies in Pune, India compared to Europeans
    Giriraj R Chandak
    Genome Research Group, Centre for Cellular and Molecular Biology, Hyderabad, India
    BMC Med Genet 7:76. 2006
    ..There are few studies of these variants in South Asians. We investigated whether the two APOA5 variants also show similar association with various lipid parameters in Indian population as in the UK white subjects...
  6. pmc Piecing together the FTO jigsaw
    Timothy M Frayling
    Peninsula College of Medicine and Dentistry, University of Exeter, Magdalen Road, Exeter EX1 2LU, UK
    Genome Biol 12:104. 2011
    ..Two recent studies of the FTO gene provide more information on how it affects body mass index...
  7. ncbi request reprint A new era in finding Type 2 diabetes genes-the unusual suspects
    T M Frayling
    Peninsula Medical School, University of Exeter, Exeter, UK
    Diabet Med 24:696-701. 2007
    ..In this review I discuss why this year is the start of a new era in our understanding of Type 2 diabetes genes and how this may lead to improved patient care...
  8. ncbi request reprint Genome-wide association studies provide new insights into type 2 diabetes aetiology
    Timothy M Frayling
    Genetics of Complex Traits, Institute of Biomedical and Clinical Sciences, Peninsula Medical School, University of Exeter, Exeter EX1 2LV, UK
    Nat Rev Genet 8:657-62. 2007
    ..One of these regions, the fat mass and obesity associated gene (FTO), represents by far the best example of an association between common variation and fat mass in the general population...
  9. pmc An interleukin-18 polymorphism is associated with reduced serum concentrations and better physical functioning in older people
    Timothy M Frayling
    Peninsula Medical School, Exeter, United Kingdom
    J Gerontol A Biol Sci Med Sci 62:73-8. 2007
    ..The role of common variation in the IL-18 gene on serum concentrations and functioning in old age is unknown...
  10. ncbi request reprint Commentary: Genetic association studies see light at the end of the tunnel
    Timothy M Frayling
    Genetics of Complex Traits, Peninsula Medical School, University of Exeter, EX1 2LU, UK
    Int J Epidemiol 37:133-5. 2008
  11. ncbi request reprint Genetic studies of diabetes following the advent of the genome-wide association study: where do we go from here?
    T M Frayling
    Genetics of Complex Traits, Institute of Biomedical and Clinical Sciences, Peninsula Medical School, Magdalen Road, Exeter EX1 2LU, UK
    Diabetologia 50:2229-33. 2007
  12. doi request reprint A genetic link between type 2 diabetes and prostate cancer
    T M Frayling
    Genetics of Complex Traits, Peninsula College of Medicine and Dentistry, University of Exeter, Magdalen Road, Exeter, UK
    Diabetologia 51:1757-60. 2008
    ..These findings are unlikely to completely explain the epidemiological association between the two diseases but they provide new insight into a possible direct causal link, rather than one that is confounded or biased in some way...
  13. pmc Polygenic risk variants for type 2 diabetes susceptibility modify age at diagnosis in monogenic HNF1A diabetes
    Hana Lango Allen
    Genetics of Complex Traits, Peninsula College of Medicine and Dentistry, University of Exeter, Exeter, U K
    Diabetes 59:266-71. 2010
    ..We investigated the hypothesis that common polygenic variants that predispose to type 2 diabetes might account for the difference in age at diagnosis...
  14. pmc Assessing the combined impact of 18 common genetic variants of modest effect sizes on type 2 diabetes risk
    Hana Lango
    Genetics of Complex Traits, Institute of Biomedical and Clinical Science, Peninsula Medical School, Exeter, UK
    Diabetes 57:3129-35. 2008
    ..Here, we assess the ability of 18 confirmed type 2 diabetes variants to differentiate between type 2 diabetic case and control subjects...
  15. pmc Type 2 diabetes risk alleles are associated with reduced size at birth
    Rachel M Freathy
    Genetics of Complex Traits, Institute of Biomedical and Clinical Science, Peninsula Medical School, Exeter, UK
    Diabetes 58:1428-33. 2009
    ..We tested whether common genetic variants that predispose to type 2 diabetes also reduce birth weight...
  16. ncbi request reprint A large-scale association analysis of common variation of the HNF1alpha gene with type 2 diabetes in the U.K. Caucasian population
    Michael N Weedon
    Institute of Biomedical and Clinical Science, Peninsula Medical School, Exeter, UK
    Diabetes 54:2487-91. 2005
    ..31 [1.08-1.59], P = 0.007). Further studies are required to investigate this association, demonstrating the difficulty of defining the role of rare (<5%) alleles in type 2 diabetes risk...
  17. pmc Combining information from common type 2 diabetes risk polymorphisms improves disease prediction
    Michael N Weedon
    Department of Diabetes Research and Vascular Medicine, Peninsula Medical School, Exeter, United Kingdom
    PLoS Med 3:e374. 2006
    ..The value of analyzing multiple alleles simultaneously is not well studied. This is often because, for any given disease, very few common risk alleles have been confirmed...
  18. pmc Effects of the diabetes linked TCF7L2 polymorphism in a representative older population
    David Melzer
    Peninsula Medical School, RD and E Wonford Site, Barrack Road, Exeter, EX2 5DW, UK
    BMC Med 4:34. 2006
    ..We aimed to estimate associations of the marker rs7903146 (C/T) polymorphism with fasting glucose, lipids, diabetes prevalence and complications in an older general population...
  19. pmc A common variant in the FTO gene is associated with body mass index and predisposes to childhood and adult obesity
    Timothy M Frayling
    Genetics of Complex Traits, Institute of Biomedical and Clinical Science, Peninsula Medical School, Magdalen Road, Exeter, UK
    Science 316:889-94. 2007
    ..67-fold increased odds of obesity when compared with those not inheriting a risk allele. This association was observed from age 7 years upward and reflects a specific increase in fat mass...
  20. pmc A study of association between common variation in the growth hormone-chorionic somatomammotropin hormone gene cluster and adult fasting insulin in a UK Caucasian population
    Rachel M Freathy
    Institute of Biomedical and Clinical Science, Peninsula Medical School, Exeter, UK
    J Negat Results Biomed 5:18. 2006
    ..We genotyped 1396 subjects (fathers, mothers and children) from a consecutive birth study for the CSH1.01 marker and analysed genotypes for association with 1-year weight in boys and fasting insulin in fathers...
  21. pmc Stratifying type 2 diabetes cases by BMI identifies genetic risk variants in LAMA1 and enrichment for risk variants in lean compared to obese cases
    John R B Perry
    Genetics of Complex Traits, Peninsula Medical School, University of Exeter, Exeter, United Kingdom
    PLoS Genet 8:e1002741. 2012
    ..08], P = 2.2×10⁻¹⁶. This study provides evidence that stratification of type 2 diabetes cases by BMI may help identify additional risk variants and that lean cases may have a stronger genetic predisposition to type 2 diabetes...
  22. pmc Common variation in the FTO gene alters diabetes-related metabolic traits to the extent expected given its effect on BMI
    Rachel M Freathy
    Institute of Biomedical and Clinical Science, Peninsula Medical School, Magdalen Rd, Exeter, EX1 2LU, UK
    Diabetes 57:1419-26. 2008
    ..Increased BMI is associated with diabetes risk factors, including raised insulin, glucose, and triglycerides. We aimed to test whether FTO genotype is associated with variation in these metabolic traits...
  23. pmc The functional "KL-VS" variant of KLOTHO is not associated with type 2 diabetes in 5028 UK Caucasians
    Rachel M Freathy
    Institute of Biomedical and Clinical Science, Peninsula Medical School, Exeter, UK
    BMC Med Genet 7:51. 2006
    ..We performed a large case-control and family-based study to test the hypothesis that KL-VS is associated with type 2 diabetes in a UK Caucasian population...
  24. ncbi request reprint Common variants of the hepatocyte nuclear factor-4alpha P2 promoter are associated with type 2 diabetes in the U.K. population
    Michael N Weedon
    Department of Diabetes Research and Vascular Medicine, Peninsula Medical School, Barrack Road, Exeter, UK
    Diabetes 53:3002-6. 2004
    ..1-linked cases. In conclusion, we have replicated the association of the HNF4alpha P2 promoter haplotype with type 2 diabetes in a U.K. Caucasian population where there is no evidence of linkage to 20q...
  25. ncbi request reprint Functional variation in VEGF is not associated with type 2 diabetes in a United Kingdom Caucasian population
    Rachel M Freathy
    Institute of Biomedical and Clinical Science, Peninsula Medical School, Exeter, United Kingdom
    JOP 7:295-302. 2006
    ..The single nucleotide polymorphisms C-2578A (rs699947), G-1154A (rs1570360) and G-634C (rs2010963) in the 5'-region of VEGF are associated with altered serum concentrations of the protein...
  26. ncbi request reprint No evidence of association of ENPP1 variants with type 2 diabetes or obesity in a study of 8,089 U.K. Caucasians
    Michael N Weedon
    Molecular Genetics, Peninsula Medical School, Barrack Road, Exeter, EX2 5DW, UK
    Diabetes 55:3175-9. 2006
    ..25 [1.10-1.43], P = 0.0007), although there was some evidence of publication bias. In conclusion, we find no evidence that previously associated variants of ENPP1 are associated with type 2 diabetes or obesity in the U.K. population...
  27. ncbi request reprint Lack of support for a role of the insulin gene variable number of tandem repeats minisatellite (INS-VNTR) locus in fetal growth or type 2 diabetes-related intermediate traits in United Kingdom populations
    Simon M S Mitchell
    Department of Diabetes and Vascular Medicine, Peninsula Medical School, Exeter, United Kingdom EX2 5AX
    J Clin Endocrinol Metab 89:310-7. 2004
    ..In the largest study to date, we found a lack of support for a role for INS-VNTR in fetal growth and nominal association with type 2 diabetes-related intermediate traits...
  28. pmc Allelic drop-out may occur with a primer binding site polymorphism for the commonly used RFLP assay for the -1131T>C polymorphism of the Apolipoprotein AV gene
    Kirsten J Ward
    Institute of Biomedical and Clinical Science, Peninsula Medical School, Exeter, UK
    Lipids Health Dis 5:11. 2006
    ..Our results also emphasise the need for careful quality control in all molecular genetic studies, particularly while transferring genotyping methods between various ethnic groups...
  29. pmc Interrogating type 2 diabetes genome-wide association data using a biological pathway-based approach
    John R B Perry
    Genetics of Complex Traits, Institute of Biomedical and Clinical Science, Peninsula Medical School, Magdalen Road, Exeter, UK
    Diabetes 58:1463-7. 2009
    ..In a complementary approach to these single-marker studies, we attempted to identify biological pathways associated with type 2 diabetes. This approach could allow us to identify additional risk loci...
  30. pmc Type 2 diabetes TCF7L2 risk genotypes alter birth weight: a study of 24,053 individuals
    Rachel M Freathy
    Institute of Biomedical and Clinical Science, Peninsula Medical School, Exeter, UK
    Am J Hum Genet 80:1150-61. 2007
    ..In conclusion, we have identified the first type 2 diabetes-susceptibility allele to be reproducibly associated with birth weight. Common gene variants can substantially influence normal birth-weight variation...
  31. pmc A common genetic variant in the 15q24 nicotinic acetylcholine receptor gene cluster (CHRNA5-CHRNA3-CHRNB4) is associated with a reduced ability of women to quit smoking in pregnancy
    Rachel M Freathy
    Genetics of Complex Traits, Peninsula Medical School, Institute of Biomedical and Clinical Science, Magdalen Road, Exeter EX1 2LU, UK
    Hum Mol Genet 18:2922-7. 2009
    ..Our data support the role of genetic factors in influencing smoking cessation during pregnancy...
  32. pmc Allelic heterogeneity and more detailed analyses of known loci explain additional phenotypic variation and reveal complex patterns of association
    Andrew R Wood
    Genetics of Complex Traits, Peninsula College of Medicine and Dentistry, University of Exeter, Exeter EX1 2LU, UK
    Hum Mol Genet 20:4082-92. 2011
    ....
  33. ncbi request reprint Young-onset type 2 diabetes families are the major contributors to genetic loci in the Diabetes UK Warren 2 genome scan and identify putative novel loci on chromosomes 8q21, 21q22, and 22q11
    Timothy M Frayling
    Department of Diabetes and Vascular Medicine, Peninsula Medical School, Exeter, UK
    Diabetes 52:1857-63. 2003
    ..Our data confirm our hypothesis that families segregating young-onset type 2 diabetes represent a more powerful resource for defining susceptibility genes by linkage...
  34. pmc Human aging is characterized by focused changes in gene expression and deregulation of alternative splicing
    Lorna W Harries
    Institute of Biomedical and Clinical Sciences, Peninsula College of Medicine and Dentistry, University of Exeter, Exeter, UK
    Aging Cell 10:868-78. 2011
    ..05]. This is supported by our observation of age-associated disruption to the balance of alternatively expressed isoforms for selected genes, suggesting that modification of mRNA processing may be a feature of human aging...
  35. pmc A common variant of HMGA2 is associated with adult and childhood height in the general population
    Michael N Weedon
    Genetics of Complex Traits, Institute of Biomedical and Clinical Science, Peninsula Medical School, Magdalen Road, Exeter EX1 2LU, UK
    Nat Genet 39:1245-50. 2007
    ..There are few examples of common genetic variants reproducibly associated with human quantitativetraits; these results represent, to our knowledge, the first consistently replicated association with adult and childhood height...
  36. pmc Genome-wide association analysis identifies 20 loci that influence adult height
    Michael N Weedon
    Genetics of Complex Traits, Institute of Biomedical and Clinical Science, Peninsula Medical School, Magdalen Road, Exeter EX1 2LU, UK
    Nat Genet 40:575-83. 2008
    ..Finally, our results provide insights into the genetic architecture of a classic quantitative trait...
  37. pmc Variants in ADCY5 and near CCNL1 are associated with fetal growth and birth weight
    Rachel M Freathy
    Genetics of Complex Traits, Peninsula College of Medicine and Dentistry, University of Exeter, Exeter, UK
    Nat Genet 42:430-5. 2010
    ..The impact on birth weight is similar to that of a mother smoking 4-5 cigarettes per day in the third trimester of pregnancy...
  38. ncbi request reprint Combining genome and mouse knockout expression data to highlight binding sites for the transcription factor HNF1alpha
    Christopher R Lockwood
    Department of Diabetes and Vascular Medicine, Peninsular Medical School, University of Exeter, Barrack Rd, Exeter EX2 5AX, United Kingdom
    In Silico Biol 3:57-70. 2003
    ..In conclusion, gene expression data from transgenic animals lacking a transcription factor can be used to identify DNA binding sites for that factor...
  39. pmc Hundreds of variants clustered in genomic loci and biological pathways affect human height
    Hana Lango Allen
    Genetics of Complex Traits, Peninsula College of Medicine and Dentistry, University of Exeter, Exeter EX1 2LU, UK
    Nature 467:832-8. 2010
    ....
  40. pmc Imputation of variants from the 1000 Genomes Project modestly improves known associations and can identify low-frequency variant-phenotype associations undetected by HapMap based imputation
    Andrew R Wood
    Genetics of Complex Traits, Institute of Biomedical and Clinical Sciences, Peninsula College of Medicine and Dentistry, University of Exeter, Exeter, United Kingdom
    PLoS ONE 8:e64343. 2013
    ..007) and alpha1-antitrypsin that predisposes to emphysema (P = 2.5×10(-12)). Our data provide important proof of principle that 1000 Genomes imputation will detect novel, low frequency-large effect associations...
  41. ncbi request reprint A genome-wide scan in families with maturity-onset diabetes of the young: evidence for further genetic heterogeneity
    Timothy M Frayling
    Department of Diabetes and Vascular Medicine, Postgraduate School of Medicine and Health Science, University of Exeter, Exeter, U K
    Diabetes 52:872-81. 2003
    ..88 at 169-175 cM), and to chromosomes 3 (heterogeneity LOD [HLOD] score 1.27 at 124 cM) and 5 (HLOD score 1.22 at 175 cM) in 14 more strictly defined families. Our results provide evidence for further heterogeneity in MODY...
  42. pmc Polymorphisms in LMNA and near a SERPINA gene cluster are associated with cognitive function in older people
    Christie Cluett
    Peninsula Medical School, RD and E Wonford Site, Exeter, UK
    Neurobiol Aging 31:1563-8. 2010
    ..The mechanisms underlying the associations with cognitive impairment and LOAD require further elucidation, but both genes are interesting candidates for involvement in age-related cognitive impairment...
  43. pmc A genome-wide association study identifies protein quantitative trait loci (pQTLs)
    David Melzer
    Department of Epidemiology and Public Health, Institute of Biomedical and Clinical Sciences, Peninsula College of Medicine and Dentistry, University of Exeter, Devon, United Kingdom
    PLoS Genet 4:e1000072. 2008
    ..These include the presence of strong genetic effects in cis locations. The identification of protein quantitative trait loci (pQTLs) may be a powerful complementary method of improving our understanding of disease pathways...
  44. pmc Genetic variation in the 15q25 nicotinic acetylcholine receptor gene cluster (CHRNA5-CHRNA3-CHRNB4) interacts with maternal self-reported smoking status during pregnancy to influence birth weight
    Jessica Tyrrell
    European Centre for Environment and Human Health, University of Exeter, The Knowledge Spa, Truro, UK
    Hum Mol Genet 21:5344-58. 2012
    ....
  45. doi request reprint Phosphodiesterase 8B gene polymorphism is associated with subclinical hypothyroidism in pregnancy
    Beverley M Shields
    Peninsula National Institute for Health Research Clinical Research Facility, Peninsula Medical School, Exeter University, Exeter EX2 5DW, United Kingdom
    J Clin Endocrinol Metab 94:4608-12. 2009
    ..We aimed to assess whether genetic variation in TSH due to the rs4704397 genotype affects the number of individuals classified as having subclinical hypothyroidism in pregnancy...
  46. pmc Genetic evidence that raised sex hormone binding globulin (SHBG) levels reduce the risk of type 2 diabetes
    John R B Perry
    Genetics of Complex Traits, Peninsula College of Medicine and Dentistry, University of Exeter, Magdalen Road, Exeter, UK
    Hum Mol Genet 19:535-44. 2010
    ..Our results, together with those from another recent genetic study, strengthen evidence that SHBG and sex hormones are involved in the aetiology of type 2 diabetes...
  47. pmc The 9p21 myocardial infarction risk allele increases risk of peripheral artery disease in older people
    Christie Cluett
    Peninsula Medical School, Exeter, United Kingdom
    Circ Cardiovasc Genet 2:347-53. 2009
    ..09 for PAD (P=0.075). We aimed at estimating the association of this variant with an Ankle-Brachial Index (ABI) and PAD in 3 older populations...
  48. pmc Mendelian randomization studies do not support a role for raised circulating triglyceride levels influencing type 2 diabetes, glucose levels, or insulin resistance
    N Maneka G De Silva
    Genetics of Complex Traits, Institute of Biomedical and Clinical Sciences, Peninsula College of Medicine and Dentistry, University of Exeter, Exeter, UK
    Diabetes 60:1008-18. 2011
    ..We aimed to use Mendelian randomization to test the hypothesis that raised circulating triglyceride levels causally influence the risk of type 2 diabetes and raise normal fasting glucose levels and hepatic insulin resistance...
  49. ncbi request reprint Variants in the aromatase gene and on the Y-chromosome are not associated with adult height or insulin resistance in a UK population
    Michael N Weedon
    Centre for Molecular Genetics, Peninsula Medical School, Exeter and Regional Endocrine Laboratory, University Hospital Birmingham NHS Trust, UK
    Clin Endocrinol (Oxf) 59:175-9. 2003
    ....
  50. ncbi request reprint Insights on pathogenesis of type 2 diabetes from MODY genetics
    Michael N Weedon
    Institute of Biomedical and Clinical Sciences, Peninsula College of Medicine and Dentistry, Peninsula Medical School, St Lukes Campus, Magdalen Road, Exeter EX1 2LU, UK
    Curr Diab Rep 7:131-8. 2007
    ..We review recent studies that suggest that common MODY gene variation contributes modestly to the heritability of type 2 diabetes...
  51. doi request reprint New gene variants alter type 2 diabetes risk predominantly through reduced beta-cell function
    John R B Perry
    Genetics of Complex Traits, Institute of Biomedical and Clinical Science, Peninsula Medical School, Exeter, UK
    Curr Opin Clin Nutr Metab Care 11:371-7. 2008
    ..In this study, we focus on explaining the genome-wide approach that has led to most of these discoveries and discuss some of the early insights the new gene loci have provided into the aetiology of type 2 diabetes...
  52. ncbi request reprint Activating mutations in the gene encoding the ATP-sensitive potassium-channel subunit Kir6.2 and permanent neonatal diabetes
    Anna L Gloyn
    Institute of Biomedical and Clinical Science, Peninsula Medical School, Exeter, United Kingdom
    N Engl J Med 350:1838-49. 2004
    ..2 subunit of this channel (KCNJ11) cause neonatal diabetes...
  53. pmc Mendelian randomization studies do not support a causal role for reduced circulating adiponectin levels in insulin resistance and type 2 diabetes
    Hanieh Yaghootkar
    Genetics of Complex Traits, University of Exeter Medical School, Exeter, U K
    Diabetes 62:3589-98. 2013
    ..95-1.04; 15,960 case subjects vs. 64,731 control subjects). These results do not provide any consistent evidence that interventions aimed at increasing adiponectin levels will improve insulin sensitivity or risk of type 2 diabetes. ..
  54. doi request reprint Novel biological insights emerging from genetic studies of type 2 diabetes and related metabolic traits
    N Maneka G De Silva
    Genetics of Complex Traits, Institute of Biomedical and Clinical Science, Peninsula College of Medicine and Dentistry, University of Exeter, Exeter, UK
    Curr Opin Lipidol 21:44-50. 2010
    ..The purpose of this review is to update the reader with the most relevant findings, with a particular emphasis on type 2 diabetes (T2D) and glucose metabolism, and discuss some of the biological implications of the genetic findings...
  55. ncbi request reprint Large-scale association studies of variants in genes encoding the pancreatic beta-cell KATP channel subunits Kir6.2 (KCNJ11) and SUR1 (ABCC8) confirm that the KCNJ11 E23K variant is associated with type 2 diabetes
    Anna L Gloyn
    Centre for Molecular Genetics, Peninsula Medical School, Exeter, UK
    Diabetes 52:568-72. 2003
    ..000002); but the ABCC8 variants were not associated. Our results confirm that E23K increases risk of type 2 diabetes and show that large-scale association studies are important for the identification of diabetes susceptibility alleles...
  56. ncbi request reprint Intrauterine hyperglycemia is associated with an earlier diagnosis of diabetes in HNF-1alpha gene mutation carriers
    Amanda Stride
    Department of Diabetes and Vascular Medicine, University of Exeter, Devon, UK
    Diabetes Care 25:2287-91. 2002
    ....
  57. ncbi request reprint In silico searching of human and mouse genome data identifies known and unknown HNF1 binding sites upstream of beta-cell genes
    Christopher R Lockwood
    Diabetes and Vascular Medicine, Peninsular Medical School, Exeter, UK
    Mol Genet Metab 78:145-51. 2003
    ..This should help in designing experiments to discover the mechanisms of beta-cell dysfunction due to HNF1 disruption...
  58. doi request reprint Parental diabetes and birthweight in 236 030 individuals in the UK Biobank Study
    Jessica S Tyrrell
    European Centre for Environment and Human Health, University of Exeter Medical School, Truro, UK, Genetics of Complex Traits, University of Exeter Medical School, Exeter, UK and Molecular Genetics, Wonford Building, University of Exeter Medical School, Exeter, UK
    Int J Epidemiol 42:1714-23. 2013
    ..We aimed to use the UK Biobank data to study the well-established, but poorly understood, association between low birthweight and type 2 diabetes...
  59. pmc Genetic variants associated with glycine metabolism and their role in insulin sensitivity and type 2 diabetes
    Weijia Xie
    Genetics of Complex Traits, Peninsula School of Medicine, University of Exeter, Exeter, UK
    Diabetes 62:2141-50. 2013
    ..Genetic variants associated with genes in the glycine biosynthesis pathways do not provide consistent evidence for a role of glycine in diabetes-related traits...
  60. ncbi request reprint The transcription factor 7-like 2 (TCF7L2) gene is associated with Type 2 diabetes in UK community-based cases, but the risk allele frequency is reduced compared with UK cases selected for genetic studies
    N M G De Silva
    Peninsula Medical School, Exeter, UK
    Diabet Med 24:1067-72. 2007
    ..We aimed to compare the impact of TCF7L2 in UK community-based Type 2 diabetic subjects with that in subjects ascertained for genetic studies...
  61. doi request reprint Reaching new heights: insights into the genetics of human stature
    Michael N Weedon
    Genetics of Complex Traits, Institute of Biomedical and Clinical Science, Peninsula College of Medicine and Dentistry, Magdalen Road, Exeter, EX1 2LU, UK
    Trends Genet 24:595-603. 2008
    ..We also discuss the strong probability of finding several hundred more such loci in the near future...
  62. pmc A common variant of the interleukin 6 receptor (IL-6r) gene increases IL-6r and IL-6 levels, without other inflammatory effects
    S Rafiq
    Peninsula Medical School, Institute of Biomedical and Clinical Science, Exeter, UK
    Genes Immun 8:552-9. 2007
    ..A common variant of the IL-6r gene results in major changes in IL-6r and IL-6 serum levels, but with no apparent effect on gp130 levels or on inflammatory status in the general population...
  63. ncbi request reprint The role of transcription factors in maturity-onset diabetes of the young
    Simon M S Mitchell
    Department of Diabetes and Vascular Medicine, University of Exeter, Barrack Road, EX2 5AX, Exeter, UK
    Mol Genet Metab 77:35-43. 2002
    ....
  64. ncbi request reprint The role of the HNF4alpha enhancer in type 2 diabetes
    Simon M S Mitchell
    Department of Diabetes and Vascular Medicine, University of Exeter, Barrack Road, EX2 5DW, UK
    Mol Genet Metab 76:148-51. 2002
    ..No variants of the enhancer element were found in this population. We conclude that variation in the HNF4alpha enhancer element is not a common cause of susceptibility to type 2 diabetes...
  65. pmc Circulating beta-carotene levels and type 2 diabetes-cause or effect?
    J R B Perry
    Peninsula Medical School, Exeter, UK
    Diabetologia 52:2117-21. 2009
    ..In this study we used a Mendelian randomisation approach to provide evidence for or against the causal role of the antioxidant vitamin beta-carotene in type 2 diabetes...
  66. ncbi request reprint No evidence for linkage at candidate type 2 diabetes susceptibility loci on chromosomes 12 and 20 in United Kingdom Caucasians
    T M Frayling
    Department of Diabetes and Vascular Medicine, School of Postgraduate Medicine and Health Sciences, University of Exeter, United Kingdom
    J Clin Endocrinol Metab 85:853-7. 2000
    ..We have not confirmed in United Kingdom Caucasians the evidence for linkage previously reported on 12q and 20q. Our results highlight further the problems of replicating previous positive linkage results across different ethnic groups...
  67. pmc Studies of association between the gene for calpain-10 and type 2 diabetes mellitus in the United Kingdom
    J C Evans
    Department of Diabetes and Vascular Medicine, School of Postgraduate Medicine and Health Sciences, University of Exeter, Exeter, EX2 5AX, United Kingdom
    Am J Hum Genet 69:544-52. 2001
    ..In conclusion, we were not able to replicate the association of the specific calpain-10 alleles identified by Horikawa et al. but suggest that other alleles at this locus may increase type 2 diabetes risk in the U.K. population...
  68. ncbi request reprint Association of calpain-10 gene with microvascular function
    A C Shore
    Institute of Biomedical and Clinical Science, Peninsula Medical School, Barrack Road, Exeter, Devon, EX2 5AX, UK
    Diabetologia 45:899-904. 2002
    ..Alterations in microvascular function could contribute to insulin resistance. This study investigated whether polymorphisms in the Calpain-10 gene influence microvascular function...
  69. pmc Gene variants influencing measures of inflammation or predisposing to autoimmune and inflammatory diseases are not associated with the risk of type 2 diabetes
    S Rafiq
    Peninsula Medical School, University of Exeter, Magdalen Road, Exeter, EX1 2LU, UK
    Diabetologia 51:2205-13. 2008
    ..We tested the hypothesis that common gene variants known to alter circulating levels of inflammatory proteins, or known to alter autoimmune-related disease risk, influence type 2 diabetes risk...
  70. ncbi request reprint The role of genetic susceptibility in the association of low birth weight with type 2 diabetes
    T M Frayling
    Department of Diabetes and Vascular Medicine, School of Postgraduate Medicine and Health Sciences, University of Exeter, Exeter, UK
    Br Med Bull 60:89-101. 2001
    ..All previously described associations between birth weight and type 2 diabetes have required many hundreds of subjects and it is likely that the geneticists and the 'programmists' are trying to identify very subtle physiological effects...
  71. ncbi request reprint Allelic drop-out in exon 2 of the hepatocyte nuclear factor-1alpha gene hinders the identification of mutations in three families with maturity-onset diabetes of the young
    S Ellard
    Department of Diabetes and Vascular Medicine, School of Postgraduate Medicine and Health Sciences, University of Exeter, UK
    Diabetes 48:921-3. 1999
  72. pmc Assessing association of common variation in the C1Q gene cluster with systemic lupus erythematosus
    S Rafiq
    Institute of Biomedical and Clinical Sciences, Peninsula Medical School, University of Exeter, Exeter, UK
    Clin Exp Immunol 161:284-9. 2010
    ..This is in contrast to other cohorts, in which single variants associated with C1Q, C3 and C4 levels and nephritis have been studied and shown associations...
  73. ncbi request reprint beta-cell genes and diabetes: molecular and clinical characterization of mutations in transcription factors
    T M Frayling
    Centre for Molecular Genetics, School of Postgraduate Medicine and Health Sciences, University of Exeter, Devon, UK
    Diabetes 50:S94-100. 2001
    ..There is little evidence to indicate that different mutations within the same gene have different phenotypes...
  74. ncbi request reprint Common genetic variation in the gene encoding interleukin-1-receptor antagonist (IL-1RA) is associated with altered circulating IL-1RA levels
    S Rafiq
    Peninsula College of Medicine and Dentistry, University of Exeter, Magdalen Road, Exeter, UK
    Genes Immun 8:344-51. 2007
    ..03), alpha-2 macroglobulin (P=0.008) and adiponectin (P=0.007) serum levels. In conclusion, common variation across the IL-1RN gene is strongly associated with IL-1RA levels...
  75. ncbi request reprint Rare variants identified in the HNF- 4 alpha beta-cell-specific promoter and alternative exon 1 lack biological significance in maturity onset diabetes of the young and young onset Type II diabetes
    S M S Mitchell
    Department of Diabetes and Vascular Medicine, University of Exeter, Exeter, UK
    Diabetologia 45:1344-8. 2002
    ..Linkage to this region in studies of Type II diabetes makes the P2 region a strong candidate for a role in Type II diabetes susceptibility...
  76. ncbi request reprint A rapid screening method for hepatocyte nuclear factor 1 alpha frameshift mutations; prevalence in maturity-onset diabetes of the young and late-onset non-insulin dependent diabetes
    T M Frayling
    Division of Molecular Genetics, University of Exeter, UK
    Hum Genet 101:351-4. 1997
    ..Our results indicate that the prevalence of the nine frameshift mutations in strictly defined UK MODY is 18%, with the P291fsinsC mutation alone having a frequency of 13%...
  77. ncbi request reprint Association studies of insulin receptor substrate 1 gene (IRS1) variants in type 2 diabetes samples enriched for family history and early age of onset
    Eleftheria Zeggini
    Oxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford, Oxford, UK
    Diabetes 53:3319-22. 2004
    ....
  78. pmc Replication of genome-wide association signals in UK samples reveals risk loci for type 2 diabetes
    Eleftheria Zeggini
    Oxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford, Churchill Hospital, Oxford, OX3 7LJ, UK
    Science 316:1336-41. 2007
    ..The regions identified underscore the importance of pathways influencing pancreatic beta cell development and function in the etiology of type 2 diabetes...
  79. ncbi request reprint Evidence from a large U.K. family collection that genes influencing age of onset of type 2 diabetes map to chromosome 12p and to the MODY3/NIDDM2 locus on 12q24
    Steven Wiltshire
    Wellcome Trust Centre for Human Genetics, Oxford, U K
    Diabetes 53:855-60. 2004
    ..These data provide additional evidence that genes mapping to these chromosomal regions are involved in the susceptibility to, and/or development of, type 2 diabetes...
  80. pmc Meta-analysis and a large association study confirm a role for calpain-10 variation in type 2 diabetes susceptibility
    Michael N Weedon
    Am J Hum Genet 73:1208-12. 2003
  81. ncbi request reprint Association and haplotype analysis of the insulin-degrading enzyme (IDE) gene, a strong positional and biological candidate for type 2 diabetes susceptibility
    Christopher J Groves
    Oxford Centre for Diabetes, Endocrinology and Metabolism, Churchill Site, Old Road, Headington, Oxford OX3 7LJ, U K
    Diabetes 52:1300-5. 2003
    ....
  82. ncbi request reprint Genetic variation in the small heterodimer partner gene and young-onset type 2 diabetes, obesity, and birth weight in U.K. subjects
    Simon M S Mitchell
    Centre for Molecular Genetics, Peninsula Medical School, Barrack Road, Exeter EX2 5AX, U K
    Diabetes 52:1276-9. 2003
    ..Our study suggests that genetic variation in SHP is unlikely to be common in the predisposition to diabetes, obesity, or increased birth weight in U.K. Caucasians...
  83. ncbi request reprint A putative functional polymorphism in the IGF-I gene: association studies with type 2 diabetes, adult height, glucose tolerance, and fetal growth in U.K. populations
    Timothy M Frayling
    Department of Diabetes and Vascular Medicine, University of Exeter, Barrack Road, Exeter EX2 5AX, U K
    Diabetes 51:2313-6. 2002
    ..66). There was no association with measures of fetal growth, including birth weight (P = 0.17). Our results do not support the previous associations and suggest that the promoter microsatellite is unlikely to be functionally important...
  84. ncbi request reprint Variation within the type 2 diabetes susceptibility gene calpain-10 and polycystic ovary syndrome
    Lema Haddad
    Complex Traits Analysis Group, Department of Medicine, Imperial College Genetics and Genomics Research Institute, Imperial College School of Medicine, London W12 0NN, UK
    J Clin Endocrinol Metab 87:2606-10. 2002
    ..40-1.71). No associations were seen with intermediate traits of relevance to diabetes and PCOS pathogenesis. We have found no evidence from these analyses that CAPN10 gene variation influences susceptibility to PCOS...
  85. ncbi request reprint Association studies of genetic variation in the WFS1 gene and type 2 diabetes in U.K. populations
    Jayne A L Minton
    Section of Medical and Molecular Genetics, Department of Pediatrics and Child Health, The Medical School, University of Birmingham, Edgbaston, UK
    Diabetes 51:1287-90. 2002
    ..54%, OR 1.29 [95% CI 1.08-1.54], P = 0.0053). Our results provide the first evidence that variation in the WFS1 gene may influence susceptibility to type 2 diabetes...
  86. ncbi request reprint Variation in the calpain-10 gene affects blood glucose levels in the British population
    Stephen Lynn
    School of Clinical Medical Sciences, The Medical School, University of Newcastle upon Tyne, Newcastle upon Tyne, UK
    Diabetes 51:247-50. 2002
    ..002). We conclude that genetic variation in the CAPN10 gene influences blood glucose levels in nondiabetic British subjects and that this is due, at least in part, to the effects of calpain-10 on the early insulin secretory response...
  87. pmc Evidence for linkage of stature to chromosome 3p26 in a large U.K. Family data set ascertained for type 2 diabetes
    Steven Wiltshire
    Imperial College Genetics and Genomics Research Institute and Division of Medicine, Imperial College, London, United Kingdom
    Am J Hum Genet 70:543-6. 2002
    ..Our findings extend similar recent studies in Scandinavian and Quebecois populations, adding further evidence that height is indeed under the control of multiple genes...
  88. ncbi request reprint Genetic regulation of birth weight and fasting glucose by a common polymorphism in the islet cell promoter of the glucokinase gene
    Michael N Weedon
    Institute of Biomedical and Clinical Science, Peninsula Medical School, Barrack Road, Exeter EX2 5AX, U K
    Diabetes 54:576-81. 2005
    ..This study establishes that common genetic variation, in addition to rare mutations and environmental factors, can affect both FPG and birth weight...
  89. ncbi request reprint Association of the calpain-10 gene with type 2 diabetes in Europeans: results of pooled and meta-analyses
    Takafumi Tsuchiya
    Departments of Medicine and Human Genetics, The University of Chicago, 5841 S Maryland Ave, MC1027, Chicago, IL 60637, USA
    Mol Genet Metab 89:174-84. 2006
    ..68 (1.33-2.11), P=0.00001). The pooled and meta-analyses as well as the linkage disequilibrium and haplotype diversity studies suggest a role for genetic variation in CAPN10 affecting risk of T2D in Europeans...
  90. ncbi request reprint The fat mass- and obesity-associated locus and dietary intake in children
    Nicholas J Timpson
    MRC CAiTE Centre, Department of Social Medicine, Bristol University, Bristol, UK
    Am J Clin Nutr 88:971-8. 2008
    ..A region of chromosome 16 containing the fat mass-and obesity-associated gene (FTO) is reproducibly associated with fat mass and body mass index (BMI), risk of obesity, and adiposity...
  91. pmc Genetic determinants of ulcerative colitis include the ECM1 locus and five loci implicated in Crohn's disease
    Sheila A Fisher
    Department of Medical and Molecular Genetics, King s College London School of Medicine, 8th Floor Guy s Tower, Guy s Hospital, London SE1 9RT, UK
    Nat Genet 40:710-2. 2008
    ..These data provide the first detailed illustration of the genetic relationship between these common inflammatory bowel diseases...
  92. pmc Meta-analysis of genome-wide association data and large-scale replication identifies additional susceptibility loci for type 2 diabetes
    Eleftheria Zeggini
    Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK
    Nat Genet 40:638-45. 2008
    ..1 x 10(-9)), ADAMTS9 (P = 1.2 x 10(-8)) and NOTCH2 (P = 4.1 x 10(-8)) gene regions. Our results illustrate the value of large discovery and follow-up samples for gaining further insights into the inherited basis of T2D...
  93. pmc Population-based genome-wide association studies reveal six loci influencing plasma levels of liver enzymes
    Xin Yuan
    Genetics Division, GlaxoSmithKline, King of Prussia, PA 19406, USA
    Am J Hum Genet 83:520-8. 2008
    ..The specific associations with ALP levels may point to genes for bone or intestinal diseases...
  94. pmc Exploring the developmental overnutrition hypothesis using parental-offspring associations and FTO as an instrumental variable
    Debbie A Lawlor
    Medical Research Council Centre for Causal Analyses in Translational Epidemiology, University of Bristol, Bristol, United Kingdom
    PLoS Med 5:e33. 2008
    ..If true, this would result in the obesity epidemic progressing across generations irrespective of environmental or genetic changes. It is therefore important to robustly test this hypothesis...
  95. pmc Association scan of 14,500 nonsynonymous SNPs in four diseases identifies autoimmunity variants
    Paul R Burton
    Genetic Epidemiology Group, Department of Health Sciences, University of Leicester, Adrian Building, University Road, Leicester LE1 7RH, UK
    Nat Genet 39:1329-37. 2007
    ....
  96. ncbi request reprint Common variants of the novel type 2 diabetes genes CDKAL1 and HHEX/IDE are associated with decreased pancreatic beta-cell function
    Laura Pascoe
    Diabetes Research Group, Newcastle University, Newcastle upon Tyne, UK
    Diabetes 56:3101-4. 2007
    ..Our objective was to explore the relationships between the diabetes-associated alleles and measures of beta-cell function and whole-body insulin sensitivity...
  97. pmc Common variants in WFS1 confer risk of type 2 diabetes
    Manjinder S Sandhu
    UK Medical Research Council MRC Epidemiology Unit, Strangeways Research Laboratory, Cambridge CB1 8RN, UK
    Nat Genet 39:951-3. 2007
    ..Rare mutations in WFS1 cause Wolfram syndrome; using a gene-centric approach, we show that variation in WFS1 also predisposes to common type 2 diabetes...
  98. pmc Common variation in the LMNA gene (encoding lamin A/C) and type 2 diabetes: association analyses in 9,518 subjects
    Katharine R Owen
    Oxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford, Churchill Hospital, Old Road, Headington, Oxford OX3 7LJ, U K
    Diabetes 56:879-83. 2007
    ..However, in a meta-analysis including other available data, there is evidence that rs4641 has a modest effect on diabetes susceptibility (1.10 [1.04-1.16], P = 0.001)...
  99. ncbi request reprint Evaluation of common variants in the six known maturity-onset diabetes of the young (MODY) genes for association with type 2 diabetes
    Wendy Winckler
    Program in Medical and Population Genetics, Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA
    Diabetes 56:685-93. 2007
    ..We conclude that although rare variants in these six genes explain most cases of MODY, common variants in these same genes contribute very modestly, if at all, to the common form of type 2 diabetes...
  100. ncbi request reprint Association analysis of 6,736 U.K. subjects provides replication and confirms TCF7L2 as a type 2 diabetes susceptibility gene with a substantial effect on individual risk
    Christopher J Groves
    Oxford Centre for Diabetes, Endocrinology and Metabolism, Churchill Hospital, Headington, Oxford OX3 7LJ, UK
    Diabetes 55:2640-4. 2006
    ..4 x 10(-14) combining case-control and family-based analyses for rs4506565) exceeds genome-wide significance criteria and clearly establishes TCF7L2 as a type 2 diabetes susceptibility gene of substantial importance...
  101. ncbi request reprint Assessment of the role of common genetic variation in the transient neonatal diabetes mellitus (TNDM) region in type 2 diabetes: a comparative genomic and tagging single nucleotide polymorphism approach
    Anna L Gloyn
    Diabetes Research Laboratories, Oxford Centre for Diabetes, Endocrinology and Metabolism, Oxford, UK
    Diabetes 55:2272-6. 2006
    ..Using a study sufficiently powered to detect odds ratios of <1.2, we conclude that common variation in the TNDM region does not play an important role in the genetic susceptibility to type 2 diabetes...