Andrew T. Hattersley

FTOgene variation and measures of body mass in an African population (2009)

Hennig, Branwen J, Fulford, Anthony J, Sirugo, Giorgio, Rayco-Solon, Pura, Hattersley, Andrew T, Frayling, Timothy M, ...

Abstract Background 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...

Underlying Genetic Models of Inheritance in Established Type 2 Diabetes Associations (2009)

Salanti, Georgia, Southam, Lorraine, Altshuler, David, Ardlie, Kristin, Barroso, Inês, Boehnke, Michael, ...

For most associations of common single nucleotide polymorphisms (SNPs) with common diseases, the genetic model of inheritance is unknown. The authors extended and applied a Bayesian meta-analysis...

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 (2009)

Freathy, Rachel M., Ring, Susan M., Shields, Beverley, Galobardes, Bruna, Knight, Beatrice, Weedon, Michael N., ...

Maternal smoking during pregnancy is associated with low birth weight and adverse pregnancy outcomes. Women are more likely to quit smoking during pregnancy than at any other time in their lives, but...

Concept, design and implementation of a cardiovascular gene-centric 50 k SNP array for large-scale genomic association studies. (2008)

Keating, Brendan J, Tischfield, Sam, Murray, Sarah S, Bhangale, Tushar, Price, Thomas S, Glessner, Joseph T, ...

A wealth of genetic associations for cardiovascular and metabolic phenotypes in humans has been accumulating over the last decade, in particular a large number of loci derived from recent genome wide...

Hypomethylation of multiple imprinted loci in individuals with transient neonatal diabetes is associated with mutations in ZFP57 (2008)

Mackay, Deborah J.G., Callaway, Jonathan L.A., Marks, Sophie M., White, Helen E., Acerini, Carlo L., Boonen, Susanne E., ...

We have previously described individuals presenting with transient neonatal diabetes and showing a variable pattern of DNA hypomethylation at imprinted loci throughout the genome. We now report...

Correspondence and reprint request: (2008)

Maria Gueorguiev, Steven Wiltshire, Edwin A. Garcia, Charles Mein, Brigitte Kristen, Rebecca Allotey, ...

J Clin Endocrin Metab. First published ahead of print March 27, 2007 as doi:10.1210/jc.2006-2657

Exploring the Developmental Overnutrition Hypothesis Using Parental–Offspring Associations and FTO as an Instrumental Variable (2008)

Debbie A. Lawlor, Nicholas J. Timpson, Roger M. Harbord, Sam Leary, Andy Ness, Mark I. McCarthy, ...

BackgroundThe developmental overnutrition hypothesis suggests that greater maternal obesity during pregnancy results in increased offspring adiposity in later life. If true, this would result in the...

Hepatocyte nuclear factor-1{beta} gene deletions--a common cause of renal disease (2008)

Edghill, Emma L., Oram, Richard A., Owens, Martina, Stals, Karen L., Harries, Lorna W., Hattersley, Andrew T., ...

Background. Hepatocyte nuclear factor-1β (HNF-1β) is a critical transcription factor in pancreatic and renal development. Our previous report identified HNF-1β mutations in 23/160 patients with...

Association scan of 14,500 nonsynonymous SNPs in four diseases identifies autoimmunity variants (2007)

Newport, Melanie, Sirugo, Giorgio, Lyons, Emily, Vannberg, Fredrik, Hill, Adrian V.S., Bradbury, Linda A., ...

We have genotyped 14,436 nonsynonymous SNPs (nsSNPs) and 897 major histocompatibility complex (MHC) tag SNPs from 1,000 independent cases of ankylosing spondylitis ( AS), autoimmune thyroid disease...

Genome-wide association study of 14,000 cases of seven common diseases and 3,000 shared controls (2007)

Cardon, Lon R, Craddock, Nick, Deloukas, Panos, Duncanson, Audrey, Kwiatkowski, Dominic P, ...

There is increasing evidence that genome-wide association ( GWA) studies represent a powerful approach to the identification of genes involved in common human diseases. We describe a joint GWA study...

Association between the T-381C polymorphism of the brain natriuretic peptide gene and risk of type 2 diabetes in human populations (2007)

Meirhaeghe, Aline, Sandhu, Manjinder S., McCarthy, Mark I., De Groote, Pascal, Cottel, Dominique, Arveiler, Dominique, ...

Brain natriuretic peptide (BNP/NPPB) is a member of the natriuretic family involved in the regulation of blood pressure and blood volume as well as lipolysis control in human fat cells. Thus BNP may...

Mutations in ATP-sensitive K+ channel genes cause transient neonatal diabetes and permanent diabetes in childhood or adulthood (2007)

Flanagan, Sarah E., Patch, Ann-Marie, Mackay, Deborah J.G., Edghill, Emma L., Gloyn, Anna L., Robinson, David, ...

Transient neonatal diabetes mellitus (TNDM) is diagnosed in the first 6 months of life, with remission in infancy or early childhood. For approximately 50% of patients, their diabetes will relapse in...

Macrosomia and Hyperinsulinaemic Hypoglycaemia in Patients with Heterozygous Mutations in the HNF4A Gene (2007)

Ewan R. Pearson, Sylvia F. Boj, Anna M. Steele, Timothy Barrett, Karen Stals, Julian P. Shield, ...

BackgroundMacrosomia is associated with considerable neonatal and maternal morbidity. Factors that predict macrosomia are poorly understood. The increased rate of macrosomia in the offspring of...

Association scan of 14,500 nonsynonymous SNPs in four diseases identifies autoimmunity variants (2007)

Newport, Melanie, Sirugo, Giorgio, Lyons, Emily, Vannberg, Fredrik, Hill, Adrian V. S., Bradbury, Linda A., ...

We have genotyped 14,436 nonsynonymous SNPs (nsSNPs) and 897 major histocompatibility complex (MHC) tag SNPs from 1,000 independent cases of ankylosing spondylitis ( AS), autoimmune thyroid disease...

Association scan of 14,500 nonsynonymous SNPs in four diseases identifies autoimmunity variants (2007)

Newport, Melanie, Sirugo, Giorgio, Lyons, Emily, Vannberg, Fredrik, Hill, Adrian V. S., Bradbury, Linda A., ...

We have genotyped 14,436 nonsynonymous SNPs (nsSNPs) and 897 major histocompatibility complex (MHC) tag SNPs from 1,000 independent cases of ankylosing spondylitis ( AS), autoimmune thyroid disease...

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 (2006)

Freathy, Rachel M, Mitchell, Simon MS, Knight, Beatrice, Shields, Beverley, Weedon, Michael N, Hattersley, Andrew T, ...

Abstract Background Reduced growth during infancy is associated with adult insulin resistance. In a UK Caucasian cohort, the CSH1.01 microsatellite polymorphism in the growth hormone-chorionic...

Triglyceride associated polymorphisms of the APOA5gene have very different allele frequencies in Pune, India compared to Europeans (2006)

Chandak, Giriraj R, Ward, Kirsten J, Yajnik, Chittaranjan S, Pandit, Anand N, Bavdekar, Ashish, Joglekar, Charu V, ...

Abstract Background The APOA5 gene variants, -1131T>C and S19W, are associated with altered triglyceride concentrations in studies of subjects of Caucasian and East Asian descent. There are few...

Triglyceride associated polymorphisms of the APOA5 gene have very different allele frequencies in Pune, India compared to Europeans (2006)

Chandak, Giriraj R., Ward, Kirsten J., Yajnik, Chittaranjan S., Pandit, Anand N., Bavdekar, Ashish, Joglekar, Charu V., ...

BACKGROUND: The APOA5 gene variants, -1131T>C and S19W, are associated with altered triglyceride concentrations in studies of subjects of Caucasian and East Asian descent. There are few studies of...

Combining Information from Common Type 2 Diabetes Risk Polymorphisms Improves Disease Prediction (2006)

Michael N. Weedon, Mark I. McCarthy, Graham Hitman, Mark Walker, Christopher J. Groves, Eleftheria Zeggini, ...

BackgroundA limited number of studies have assessed the risk of common diseases when combining information from several predisposing polymorphisms. In most cases, individual polymorphisms only...

Assessing newborn body composition using principal components analysis: differences in the determinants of fat and skeletal size (2006)

Shields, Beverley M, Knight, Bridget A, Powell, Roy J, Hattersley, Andrew T, Wright, David E

Abstract Background Birth weight is a composite of skeletal size and soft tissue. These components are likely to have different growth patterns. The aim of this paper is to investigate the...

Switching from insulin to oral sulfonylureas in patients with diabetes due to Kir6.2 mutations (2006)

Pearson, Ewan R., Flechtner, Isabelle, Njølstad, Pal R., Malecki, Maciej T., Flanagan, Sarah E., Larkin, Brian, ...

BACKGROUND: Heterozygous activating mutations in KCNJ11, encoding the Kir6.2 subunit of the ATP-sensitive potassium (K(sub ATP)) channel, cause 30 to 58 percent of cases of diabetes diagnosed in...

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 (2006)

Gloyn, Anna L., Mackay, Deborah J.G., Weedon, Michael N., McCarthy, Mark I., Walker, Mark, Hitman, Graham, ...

Recent evidence supports the strong overlap between genes implicated in monogenic diabetes and susceptibility to type 2 diabetes. Transient neonatal diabetes mellitus (TNDM) is a rare disorder...

The functional "KL-VS" variant of KLOTHOis not associated with type 2 diabetes in 5028 UK Caucasians (2006)

Freathy, Rachel M, Weedon, Michael N, Melzer, David, Shields, Beverley, Hitman, Graham A, Walker, Mark, ...

Abstract Background Klotho has an important role in insulin signalling and the development of ageing-like phenotypes in mice. The common functional "KL-VS" variant in the KLOTHO ( KL ) gene is...

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 AVgene (2006)

Ward, Kirsten J, Ellard, Sian, Yajnik, Chittaranjan S, Frayling, Timothy M, Hattersley, Andrew T, Venigalla, Prathyusha NS, ...

Abstract Apolipoprotein AV (ApoAV) gene variant, -1131T>C, is associated with increased triglyceride concentrations in all ethnic groups studied. An MseI based RFLP analysis is the most commonly used...

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 (2006)

Gloyn, Anna L., Mackay, Deborah J., Weedon, Michael N., McCarthy, Mark I., Walker, Mark, Hitman, Graham, ...

Recent evidence supports the strong overlap between genes implicated in monogenic diabetes and susceptibility to type 2 diabetes. Transient neonatal diabetes mellitus (TNDM) is a rare disorder...

Isomers of the TCF1 gene encoding hepatocyte nuclear factor-1 alpha show differential expression in the pancreas and define the relationship between mutation position and clinical phenotype in monogenic diabetes (2006)

Harries, Lorna W., Ellard, Sian, Stride, Amanda, Morgan, Noel G., Hattersley, Andrew T.

The generation of multiple transcripts by mRNA processing has the potential to moderate differences in gene expression both between tissues and at different stages of development. Where gene function...

A heterozygous activating mutation in the sulphonylurea receptor SUR1 (ABCC8) causes neonatal diabetes (2006)

Proks, Peter, Arnold, Amanda L., Bruining, Jan, Girard, Christophe, Flanagan, Sarah E., Larkin, Brian, ...

Neonatal diabetes is a genetically heterogeneous disorder with nine different genetic aetiologies reported to date. Heterozygous activating mutations in the KCNJ11 gene encoding Kir6.2, the...

Isomers of the TCF1 gene encoding hepatocyte nuclear factor -1 alpha show differential expression in the pancreas and define the relationship between mutation position and clinical phenotype in monogenic diabetes (2006)

Harries, Lorna. W., Ellard, Sian, Stride, Amanda, Morgan, Noel G., Hattersley, Andrew T.

The generation of multiple transcripts by mRNA processing has the potential to moderate differences in gene expression both between tissues and at different stages of development. Where gene function...

Relapsing diabetes can result from moderately activating mutations in KCNJ11 (2005)

Gloyn, Anna L., Reimann, Frank, Girard, Christophe, Edghill, Emma L., Proks, Peter, Pearson, Ewan R., ...

Neonatal diabetes can either remit and hence be transient or else may be permanent. These two phenotypes were considered to be genetically distinct. Abnormalities of 6q24 are the commonest cause of...

C-reactive protein and its role in metabolic syndrome: mendelian randomisation study (2005)

Timpson, Nicholas J., Lawlor, Debbie A., Harbord, Roger M., Gaunt, Tom R., Day, Proflan N.M., Palmer, Lyle J., ...

BACKGROUND: Circulating C-reactive protein (CRP) is associated with the metabolic syndrome and might be causally linked to it. Our aim was to generate estimates of the association between plasma CRP...

Relapsing diabetes can result from moderately activating mutations in KCNJ11 (2005)

Gloyn, Anna L., Reimann, Frank, Girard, Christophe, Edghill, Emma L., Proks, Peter, Pearson, Ewan R., ...

Neonatal diabetes can either remit and hence be transient or else may be permanent. These two phenotypes were considered to be genetically distinct. Abnormalities of 6q24 are the commonest cause of...

Relapsing diabetes can result from moderately activating mutations in KCNJ11 (2005)

Gloyn, Anna L., Reimann, Frank, Girard, Christophe, Edghill, Emma L., Proks, Peter, Pearson, Ewan R., ...

Neonatal diabetes can either remit and hence be transient or else may be permanent. These two phenotypes were considered to be genetically distinct. Abnormalities of 6q24 are the commonest cause of...

Activating mutations in the gene encoding the ATP-sensitive potassium-channel subunit Kir6.2 and permanent neonatal diabetes (2004)

Gloyn, Anna L., Pearson, Ewan R., Antcliff, Jennifer F., Proks, Peter, Bruining, Jan, Slingerland, Annabelle S., ...

Background Patients with permanent neonatal diabetes usually present within the first three months of life and require insulin treatment. In most, the cause is unknown. Because ATP-sensitive...

Permanent neonatal diabetes due to paternal germline mosaicism for an activating mutation of the KCNJ11 gene encoding the Kir6.2 subunit of the beta-cell potassium adenosine triphosphate channel (2004)

Gloyn, Anna L., Cummings, Elizabeth A., Edghill, Emma L., Harries, Lorna W., Scott, Rachel, Costa, Teresa, ...

Activating mutations in the KCNJ11 gene encoding for the Kir6.2 subunit of the ß-cell ATP-sensitive potassium channel have recently been shown to be a common cause of permanent neonatal diabetes. In...

Permanent neonatal diabetes due to paternal germline mosaicism for an activating mutation of the KCNJ11 Gene encoding the Kir6.2 subunit of the beta-cell potassium adenosine triphosphate channel (2004)

Gloyn, Anna L., Cummings, Elizabeth A., Edghill, Emma L., Harries, Lorna W., Scott, Rachel, Costa, Teresa, ...

Activating mutations in the KCNJ11 gene encoding for the Kir6.2 subunit of the beta-cell ATP-sensitive potassium channel have recently been shown to be a common cause of permanent neonatal diabetes....

Genetic variants in Apolipoprotein AValter triglyceride concentrations in pregnancy (2003)

Ward, Kirsten J, Shields, Beverley, Knight, Beatrice, Salzmann, Maurice B, Hattersley, Andrew T, Frayling, Timothy M

Abstract Background Triglyceride concentrations are raised in pregnancy and are considered a key fetal fuel. Several gene variants are known to alter triglyceride concentrations, including those in...

The role of genetic susceptibility in the association of low birth weight with type 2 diabetes (2001)

Frayling, Timothy M, Hattersley, Andrew T

We suggest that altered fetal growth and type 2 diabetes may be two phenotypes of the same genotype – in other words the ‘thrifty phenotype’ is the result of a ‘thrifty genotype’....

Adult height and proteinuria in type 2 diabetes (2001)

Fava, Stephen, Azzopardi, Joseph, Watkins, Peter J., Hattersley, Andrew T.

Background. Short stature has been shown to be associated with proteinuria in type 1 diabetes, but no data exist with respect to type 2 diabetes. The objective of the study was to investigate the...

A distant upstream promoter of the HNF-4{alpha} gene connects the transcription factors involved in maturity-onset diabetes of the young (2001)

Thomas, Heike, Jaschkowitz, Karin, Bulman, Mike, Frayling, Timothy M., Mitchell, Simon M.S., Roosen, Simone, ...

Maturity-onset diabetes of the young (MODY) is a monogenic, autosomal dominant subtype of early-onset diabetes mellitus due to defective insulin secretion by the pancreatic &bgr;-cell in humans. Five...

Naturally occurring mutations in the human HNF4{alpha} gene impair the function of the transcription factor to a varying degree (2000)

Lausen, Jörn, Thomas, Heike, Lemm, Ira, Bulman, Michael, Borgschulze, Michael, Lingott, Anja, ...

The hepatocyte nuclear factor (HNF)4α, a member of the nuclear receptor superfamily, regulates genes that play a critical role in embryogenesis and metabolism. Recent studies have shown that...

The mutated human gene encoding hepatocyte nuclear factor 1β inhibits kidney formation in developing Xenopus embryos

Wild, Wiltrud, Pogge Von Strandmann, Elke, Nastos, Aristotelis, Senkel, Sabine, Lingott-Frieg, Anja, Bulman, Michael, ...

The transcription factor hepatocyte nuclear factor 1β (HNF1β) is a tissue-specific regulator that also plays an essential role in early development of vertebrates. In humans, four heterozygous...

Naturally occurring mutations in the human HNF4α gene impair the function of the transcription factor to a varying degree

Lausen, Jörn, Thomas, Heike, Lemm, Ira, Bulman, Michael, Borgschulze, Michael, Lingott, Anja, ...

The hepatocyte nuclear factor (HNF)4α, a member of the nuclear receptor superfamily, regulates genes that play a critical role in embryogenesis and metabolism. Recent studies have shown that...

Missense mutations in the insulin promoter factor-1 gene predispose to type 2 diabetes

Macfarlane, Wendy M., Frayling, Timothy M., Ellard, Sian, Evans, Julie C., Allen, Lisa I.S., Bulman, Michael P., ...

The transcription factor insulin promoter factor-1 (IPF-1) plays a central role in both the development of the pancreas and the regulation of insulin gene expression in the mature pancreatic β cell....

Unlocking the secrets of the pancreatic β cell: man and mouse provide the key

Hattersley, Andrew T.

Failure of the pancreas to secrete sufficient insulin results in type 2 diabetes, but the pathogenesis of pancreatic β cell dysfunction is still poorly understood. New insights into β cell failure...

Molecular basis of Kir6.2 mutations associated with neonatal diabetes or neonatal diabetes plus neurological features

Proks, Peter, Antcliff, Jennifer F., Lippiat, Jon, Gloyn, Anna L., Hattersley, Andrew T., Ashcroft, Frances M.

Inwardly rectifying potassium channels (Kir channels) control cell membrane K+ fluxes and electrical signaling in diverse cell types. Heterozygous mutations in the human Kir6.2 gene (KCNJ11), the...

Mutations in the Hepatocyte Nuclear Factor-1β Gene Are Associated with Familial Hypoplastic Glomerulocystic Kidney Disease

Bingham, Coralie, Bulman, Michael P., Ellard, Sian, Allen, Lisa I. S., Lipkin, Graham W., Hoff, William G. Van't, ...

Familial glomerulocystic kidney disease (GCKD) is a dominantly inherited condition characterized by glomerular cysts and variable renal size and function; the molecular genetic etiology is unknown....

Studies of Association between the Gene for Calpain-10 and Type 2 Diabetes Mellitus in the United Kingdom

Evans, Julie C., Frayling, Timothy M., Cassell, Paul G., Saker, Philip J., Hitman, Graham A., Walker, Mark, ...

Variation in CAPN10, the gene encoding the ubiquitously expressed cysteine protease calpain-10, has been associated with type 2 diabetes in Mexican Americans and in two northern-European populations,...

A Genomewide Scan for Loci Predisposing to Type 2 Diabetes in a U.K. Population (The Diabetes UK Warren 2 Repository): Analysis of 573 Pedigrees Provides Independent Replication of a Susceptibility Locus on Chromosome 1q

Wiltshire, Steven, Hattersley, Andrew T., Hitman, Graham A., Walker, Mark, Levy, Jonathan C., Sampson, Michael, ...

Improved molecular understanding of the pathogenesis of type 2 diabetes is essential if current therapeutic and preventative options are to be extended. To identify diabetes-susceptibility genes, we...

Understanding cystic-fibrosis-related diabetes: best thought of as insulin deficiency?

Dobson, Lee, Sheldon, Christopher D, Hattersley, Andrew T

The limited available evidence supports the use of insulin treatment in CFRD. This fits with the dominant problem in CFRD being insulin deficiency and progressive beta cell dysfunction, making...

A gating mutation at the internal mouth of the Kir6.2 pore is associated with DEND syndrome

Proks, Peter, Girard, Christophe, Haider, Shozeb, Gloyn, Anna L, Hattersley, Andrew T, Sansom, Mark S P, ...

Inwardly rectifying potassium (Kir) channels control cell membrane K+ fluxes and electrical signalling in diverse cell types. Heterozygous mutations in the human Kir6.2 gene (KCNJ11), the...

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

Ward, Kirsten J, Ellard, Sian, Yajnik, Chittaranjan S, Frayling, Timothy M, Hattersley, Andrew T, Venigalla, Prathyusha NS, ...

Apolipoprotein AV (ApoAV) gene variant, -1131T>C, is associated with increased triglyceride concentrations in all ethnic groups studied. An MseI based RFLP analysis is the most commonly used method...

Combining Information from Common Type 2 Diabetes Risk Polymorphisms Improves Disease Prediction

Weedon, Michael N, McCarthy, Mark I, Hitman, Graham, Walker, Mark, Groves, Christopher J, Zeggini, Eleftheria, ...

Combining information from several known common risk polymorphisms allows the identification of subgroups of the population with markedly differing risks of developing type 2 diabetes.

The mutated human gene encoding hepatocyte nuclear factor 1β inhibits kidney formation in developing Xenopus embryos

Wild, Wiltrud, Pogge Von Strandmann, Elke, Nastos, Aristotelis, Senkel, Sabine, Lingott-Frieg, Anja, Bulman, Michael, ...

The transcription factor hepatocyte nuclear factor 1β (HNF1β) is a tissue-specific regulator that also plays an essential role in early development of vertebrates. In humans, four heterozygous...

Naturally occurring mutations in the human HNF4α gene impair the function of the transcription factor to a varying degree

Lausen, Jörn, Thomas, Heike, Lemm, Ira, Bulman, Michael, Borgschulze, Michael, Lingott, Anja, ...

The hepatocyte nuclear factor (HNF)4α, a member of the nuclear receptor superfamily, regulates genes that play a critical role in embryogenesis and metabolism. Recent studies have shown that...

Evidence for Linkage of Stature to Chromosome 3p26 in a Large U.K. Family Data Set Ascertained for Type 2 Diabetes

Wiltshire, Steven, Frayling, Timothy M., Hattersley, Andrew T., Hitman, Graham A., Walker, Mark, Levy, Jonathan C., ...

We have analyzed data from 573 pedigrees from the United Kingdom for evidence for linkage to loci influencing adult stature. Our data set comprised 1,214 diabetic and 163 nondiabetic siblings for...

Missense mutations in the insulin promoter factor-1 gene predispose to type 2 diabetes

Macfarlane, Wendy M., Frayling, Timothy M., Ellard, Sian, Evans, Julie C., Allen, Lisa I.S., Bulman, Michael P., ...

The transcription factor insulin promoter factor-1 (IPF-1) plays a central role in both the development of the pancreas and the regulation of insulin gene expression in the mature pancreatic β cell....

Unlocking the secrets of the pancreatic β cell: man and mouse provide the key

Hattersley, Andrew T.

Failure of the pancreas to secrete sufficient insulin results in type 2 diabetes, but the pathogenesis of pancreatic β cell dysfunction is still poorly understood. New insights into β cell failure...

Molecular basis of Kir6.2 mutations associated with neonatal diabetes or neonatal diabetes plus neurological features

Proks, Peter, Antcliff, Jennifer F., Lippiat, Jon, Gloyn, Anna L., Hattersley, Andrew T., Ashcroft, Frances M.

Inwardly rectifying potassium channels (Kir channels) control cell membrane K+ fluxes and electrical signaling in diverse cell types. Heterozygous mutations in the human Kir6.2 gene (KCNJ11), the...

Mutations in the Hepatocyte Nuclear Factor-1β Gene Are Associated with Familial Hypoplastic Glomerulocystic Kidney Disease

Bingham, Coralie, Bulman, Michael P., Ellard, Sian, Allen, Lisa I. S., Lipkin, Graham W., Hoff, William G. Van't, ...

Familial glomerulocystic kidney disease (GCKD) is a dominantly inherited condition characterized by glomerular cysts and variable renal size and function; the molecular genetic etiology is unknown....

Studies of Association between the Gene for Calpain-10 and Type 2 Diabetes Mellitus in the United Kingdom

Evans, Julie C., Frayling, Timothy M., Cassell, Paul G., Saker, Philip J., Hitman, Graham A., Walker, Mark, ...

Variation in CAPN10, the gene encoding the ubiquitously expressed cysteine protease calpain-10, has been associated with type 2 diabetes in Mexican Americans and in two northern-European populations,...

A Genomewide Scan for Loci Predisposing to Type 2 Diabetes in a U.K. Population (The Diabetes UK Warren 2 Repository): Analysis of 573 Pedigrees Provides Independent Replication of a Susceptibility Locus on Chromosome 1q

Wiltshire, Steven, Hattersley, Andrew T., Hitman, Graham A., Walker, Mark, Levy, Jonathan C., Sampson, Michael, ...

Improved molecular understanding of the pathogenesis of type 2 diabetes is essential if current therapeutic and preventative options are to be extended. To identify diabetes-susceptibility genes, we...

A gating mutation at the internal mouth of the Kir6.2 pore is associated with DEND syndrome

Proks, Peter, Girard, Christophe, Haider, Shozeb, Gloyn, Anna L, Hattersley, Andrew T, Sansom, Mark S P, ...

Inwardly rectifying potassium (Kir) channels control cell membrane K+ fluxes and electrical signalling in diverse cell types. Heterozygous mutations in the human Kir6.2 gene (KCNJ11), the...

Understanding cystic-fibrosis-related diabetes: best thought of as insulin deficiency?

Dobson, Lee, Sheldon, Christopher D, Hattersley, Andrew T

The limited available evidence supports the use of insulin treatment in CFRD. This fits with the dominant problem in CFRD being insulin deficiency and progressive beta cell dysfunction, making...

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

Ward, Kirsten J, Ellard, Sian, Yajnik, Chittaranjan S, Frayling, Timothy M, Hattersley, Andrew T, Venigalla, Prathyusha NS, ...

Apolipoprotein AV (ApoAV) gene variant, -1131T>C, is associated with increased triglyceride concentrations in all ethnic groups studied. An MseI based RFLP analysis is the most commonly used method...

Combining Information from Common Type 2 Diabetes Risk Polymorphisms Improves Disease Prediction

Weedon, Michael N, McCarthy, Mark I, Hitman, Graham, Walker, Mark, Groves, Christopher J, Zeggini, Eleftheria, ...

Combining information from several known common risk polymorphisms allows the identification of subgroups of the population with markedly differing risks of developing type 2 diabetes.

Macrosomia and Hyperinsulinaemic Hypoglycaemia in Patients with Heterozygous Mutations in the HNF4A Gene

Pearson, Ewan R, Boj, Sylvia F, Steele, Anna M, Barrett, Timothy, Stals, Karen, Shield, Julian P, ...

HNF4A mutations were found to be associated with a considerable increase in birthweight and macrosomia, and were a cause of neonatal hypoglycaemia.

Prime suspect: the TCF7L2 gene and type 2 diabetes risk

Hattersley, Andrew T.

Transcription factor-7–like 2 (TCF7L2) is the most important type 2 diabetes susceptibility gene identified to date, with common intronic variants strongly associated with diabetes in all major...

The Impact of the Angiotensin-Converting Enzyme Insertion/Deletion Polymorphism on Severe Hypoglycemia in Type 2 Diabetes

Freathy, Rachel M., Lonnen, Kathryn F., Steele, Anna M., Minton, Jayne A. L., Frayling, Timothy M., Hattersley, Andrew T., ...

The insertion/deletion (I/D) polymorphism of the angiotensin-converting enzyme gene (ACE) is associated with altered serum ACE activity. Raised ACE levels and the ACE DD genotype are associated with...

Insulin gene mutations as a cause of permanent neonatal diabetes

Støy, Julie, Edghill, Emma L., Flanagan, Sarah E., Ye, Honggang, Paz, Veronica P., Pluzhnikov, Anna, ...

We report 10 heterozygous mutations in the human insulin gene in 16 probands with neonatal diabetes. A combination of linkage and a candidate gene approach in a family with four diabetic members led...

Exploring the Developmental Overnutrition Hypothesis Using Parental–Offspring Associations and FTO as an Instrumental Variable

Lawlor, Debbie A, Timpson, Nicholas J, Harbord, Roger M, Leary, Sam, Ness, Andy, McCarthy, Mark I, ...

Using parental-offspring associations and theFTO gene as an instrumental variable for maternal adiposity, Debbie Lawlor and colleagues found that greater maternal BMI during offspring development...

Increased ATPase activity produced by mutations at arginine-1380 in nucleotide-binding domain 2 of ABCC8 causes neonatal diabetes

De Wet, Heidi, Rees, Mathew G., Shimomura, Kenju, Aittoniemi, Jussi, Patch, Ann-Marie, Flanagan, Sarah E., ...

Gain-of-function mutations in the genes encoding the ATP-sensitive potassium (KATP) channel subunits Kir6.2 (KCNJ11) and SUR1 (ABCC8) are a common cause of neonatal diabetes mellitus. Here we...

Concept, Design and Implementation of a Cardiovascular Gene-Centric 50 K SNP Array for Large-Scale Genomic Association Studies

Keating, Brendan J., Tischfield, Sam, Murray, Sarah S., Bhangale, Tushar, Price, Thomas S., Glessner, Joseph T., ...

A wealth of genetic associations for cardiovascular and metabolic phenotypes in humans has been accumulating over the last decade, in particular a large number of loci derived from recent genome wide...

Genome-Wide Association Scan Meta-Analysis Identifies Three Loci Influencing Adiposity and Fat Distribution

Lindgren, Cecilia M., Heid, Iris M., Randall, Joshua C., Lamina, Claudia, Steinthorsdottir, Valgerdur, Qi, Lu, ...

To identify genetic loci influencing central obesity and fat distribution, we performed a meta-analysis of 16 genome-wide association studies (GWAS, N = 38,580) informative for adult waist...

Diabetes Susceptibility in the Canadian Oji-Cree Population Is Moderated by Abnormal mRNA Processing of HNF1A G319S Transcripts

Harries, Lorna W., Sloman, Melissa J., Sellers, Elizabeth A.C., Hattersley, Andrew T., Ellard, Sian

OBJECTIVE—The G319S HNF1A variant is associated with an increased risk of type 2 diabetes in the Canadian Oji-Cree population. We hypothesized that the variant site at the 3′ end of exon 4 might...

A mutation (R826W) in nucleotide-binding domain 1 of ABCC8 reduces ATPase activity and causes transient neonatal diabetes

De Wet, Heidi, Proks, Peter, Lafond, Mathilde, Aittoniemi, Jussi, Sansom, Mark S P, Flanagan, Sarah E, ...

Activating mutations in the pore-forming Kir6.2 (KCNJ11) and regulatory sulphonylurea receptor SUR1 (ABCC8) subunits of the KATP channel are a common cause of transient neonatal diabetes mellitus...

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

Freathy, Rachel M., Ring, Susan M., Shields, Beverley, Galobardes, Bruna, Knight, Beatrice, Weedon, Michael N., ...

Maternal smoking during pregnancy is associated with low birth weight and adverse pregnancy outcomes. Women are more likely to quit smoking during pregnancy than at any other time in their lives, but...

A Common Variation in Deiodinase 1 Gene DIO1 Is Associated with the Relative Levels of Free Thyroxine and Triiodothyronine

Panicker, Vijay, Cluett, Christie, Shields, Beverley, Murray, Anna, Parnell, Kirstie S., Perry, John R. B., ...

Introduction: Genetic factors influence circulating thyroid hormone levels, but the common gene variants involved have not been conclusively identified. The genes encoding the iodothyronine...

Coincidence of a Novel KCNJ11 Missense Variant R365H With a Paternally Inherited 6q24 Duplication in a Patient With Transient Neonatal Diabetes

Staník, Juraj, Lethby, Mark, Flanagan, Sarah E., Gašperíková, Daniela, Milošovičová, Beata, Lever, Margaret, ...

OBJECTIVE—Neonatal diabetes is a heterogeneous group of disorders with diabetes manifestation in the first 6 months of life. The most common etiology in permanent neonatal diabetes is mutations of...

Assessing the Combined Impact of 18 Common Genetic Variants of Modest Effect Sizes on Type 2 Diabetes Risk

Lango, Hana, Palmer, Colin N.A., Morris, Andrew D., Zeggini, Eleftheria, Hattersley, Andrew T., McCarthy, Mark I., ...

OBJECTIVES—Genome-wide association studies have dramatically increased the number of common genetic variants that are robustly associated with type 2 diabetes. A possible clinical use of this...

Population-Specific Risk of Type 2 Diabetes Conferred by HNF4A P2 Promoter Variants: A Lesson for Replication Studies

Barroso, Inês, Luan, Jian’an, Wheeler, Eleanor, Whittaker, Pamela, Wasson, Jon, Zeggini, Eleftheria, ...

OBJECTIVE—Single nucleotide polymorphisms (SNPs) in the P2 promoter region of HNF4A were originally shown to be associated with predisposition for type 2 diabetes in Finnish, Ashkenazi, and, more...

Wolcott-Rallison Syndrome Is the Most Common Genetic Cause of Permanent Neonatal Diabetes in Consanguineous Families

Rubio-Cabezas, Oscar, Patch, Ann-Marie, Minton, Jayne A. L., Flanagan, Sarah E., Edghill, Emma L., Hussain, Khalid, ...

Context and Objective: Mutations in EIF2AK3 cause Wolcott-Rallison syndrome (WRS), a rare recessive disorder characterized by early-onset diabetes, skeletal abnormalities, and liver dysfunction....