Publications
1182 results found
Mahajan A, Sim X, Ng HJ, et al., 2015, Identification and Functional Characterization of <i>G6PC2</i> Coding Variants Influencing Glycemic Traits Define an Effector Transcript at the <i>G6PC2</i>-<i>ABCB11</i> Locus, PLOS GENETICS, Vol: 11, ISSN: 1553-7404
- Author Web Link
- Open Access Link
- Cite
- Citations: 75
Favennec M, Hennart B, Caiazzo R, et al., 2015, The kynurenine pathway is activated in human obesity and shifted toward kynurenine monooxygenase activation, OBESITY, Vol: 23, Pages: 2066-2074, ISSN: 1930-7381
- Author Web Link
- Cite
- Citations: 165
Marquet P, Longeray P-H, Barlesi F, et al., 2015, [Not Available]., Therapie, Vol: 70, Pages: 1-10, ISSN: 0040-5957
Chandra V, Albagli-Curiel O, Hastoy B, et al., 2014, RFX6 Regulates Insulin Secretion by Modulating Ca<SUP>2+</SUP> Homeostasis in Human β Cells, CELL REPORTS, Vol: 9, Pages: 2206-2218, ISSN: 2211-1247
- Author Web Link
- Cite
- Citations: 47
Montagne L, Raimondo A, Delobel B, et al., 2014, Identification of Two Novel Loss-of-Function <i>SIM1</i> Mutations in Two Overweight Children with Developmental Delay, OBESITY, Vol: 22, Pages: 2621-2624, ISSN: 1930-7381
- Author Web Link
- Cite
- Citations: 15
Bouatia-Naji N, Dina C, Tucker N, et al., 2014, A Genome-wide Association Study of Nonsyndromic Mitral Valve Prolapse and Functional Studies of Risk Loci Provide Insight Into Underlying Biological Mechanisms, Publisher: LIPPINCOTT WILLIAMS & WILKINS, ISSN: 0009-7322
Wood AR, Esko T, Yang J, et al., 2014, Defining the role of common variation in the genomic and biological architecture of adult human height, Nature Genetics, Vol: 46, Pages: 1173-1186, ISSN: 1546-1718
Using genome-wide data from 253,288 individuals, we identified 697 variants at genome-wide significance that together explained one-fifth of the heritability for adult height. By testing different numbers of variants in independent studies, we show that the most strongly associated ~2,000, ~3,700 and ~9,500 SNPs explained ~21%, ~24% and ~29% of phenotypic variance. Furthermore, all common variants together captured 60% of heritability. The 697 variants clustered in 423 loci were enriched for genes, pathways and tissue types known to be involved in growth and together implicated genes and pathways not highlighted in earlier efforts, such as signaling by fibroblast growth factors, WNT/β-catenin and chondroitin sulfate–related genes. We identified several genes and pathways not previously connected with human skeletal growth, including mTOR, osteoglycin and binding of hyaluronic acid. Our results indicate a genetic architecture for human height that is characterized by a very large but finite number (thousands) of causal variants.
Liu C-T, Buchkovich ML, Winkler TW, et al., 2014, Multi-ethnic fine-mapping of 14 central adiposity loci, HUMAN MOLECULAR GENETICS, Vol: 23, Pages: 4738-4744, ISSN: 0964-6906
- Author Web Link
- Cite
- Citations: 35
Cauchi S, Caiazzo R, Pichard B, et al., 2014, Novel epigenetic markers of type 2 diabetes in the liver, DIABETOLOGIA, Vol: 57, Pages: S105-S105, ISSN: 0012-186X
Perimenis P, Moitrot E, Gosset P, et al., 2014, PLACENTAL PROLACTIN FAMILY LEVELS ARE MODIFIED DURING GESTATION IN THE DIABETIC RAT, International-Federation-of-Placenta-Associations (IFPA)/EPG Meeting, Publisher: W B SAUNDERS CO LTD, Pages: A30-A30, ISSN: 0143-4004
Perimenis P, Bouckenooghe T, Delplanque J, et al., 2014, Placental antiangiogenic prolactin fragments are increased in human and rat maternal diabetes, BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE, Vol: 1842, Pages: 1783-1793, ISSN: 0925-4439
- Author Web Link
- Cite
- Citations: 14
Sullivan AE, Raimondo A, Schwab TA, et al., 2014, Characterization of human variants in obesity-related SIM1 protein identifies a hot-spot for dimerization with the partner protein ARNT2, BIOCHEMICAL JOURNAL, Vol: 461, Pages: 403-412, ISSN: 0264-6021
- Author Web Link
- Cite
- Citations: 8
Ng MCY, Shriner D, Chen BH, et al., 2014, Meta-Analysis of Genome-Wide Association Studies in African Americans Provides Insights into the Genetic Architecture of Type 2 Diabetes, PLOS GENETICS, Vol: 10, ISSN: 1553-7404
- Author Web Link
- Cite
- Citations: 155
Vaxillaire M, Yengo L, Lobbens S, et al., 2014, Type 2 diabetes-related genetic risk scores associated with variations in fasting plasma glucose and development of impaired glucose homeostasis in the prospective DESIR study, DIABETOLOGIA, Vol: 57, Pages: 1601-1610, ISSN: 0012-186X
- Author Web Link
- Cite
- Citations: 32
Hoggart CJ, Venturini G, Mangino M, et al., 2014, Novel Approach Identifies SNPs in SLC2A10 and KCNK9 with Evidence for Parent-of-Origin Effect on Body Mass Index, PLOS Genetics, Vol: 10, ISSN: 1553-7390
The phenotypic effect of some single nucleotide polymorphisms (SNPs) depends on their parental origin. We present anovel approach to detect parent-of-origin effects (POEs) in genome-wide genotype data of unrelated individuals. Themethod exploits increased phenotypic variance in the heterozygous genotype group relative to the homozygous groups.We applied the method to .56,000 unrelated individuals to search for POEs influencing body mass index (BMI). Six leadSNPs were carried forward for replication in five family-based studies (of ,4,000 trios). Two SNPs replicated: the paternalrs2471083-C allele (located near the imprinted KCNK9 gene) and the paternal rs3091869-T allele (located near the SLC2A10gene) increased BMI equally (beta = 0.11 (SD), P,0.0027) compared to the respective maternal alleles. Real-time PCRexperiments of lymphoblastoid cell lines from the CEPH families showed that expression of both genes was dependent onparental origin of the SNPs alleles (P,0.01). Our scheme opens new opportunities to exploit GWAS data of unrelatedindividuals to identify POEs and demonstrates that they play an important role in adult obesity.
Dik VK, Bueno-de-Mesquita HBA, Van Oijen MGH, et al., 2014, Coffee and tea consumption, genotype- based CYP1A2 and NAT2 activity and colorectal cancer risk- Results from the EPIC cohort study, INTERNATIONAL JOURNAL OF CANCER, Vol: 135, Pages: 401-412, ISSN: 0020-7136
- Author Web Link
- Cite
- Citations: 29
Arredouani A, Yengo L, Marre M, et al., 2014, A Prospective Metabonomics Analysis Reveals New Pathways Involved in T2D Development, Publisher: AMER DIABETES ASSOC, Pages: A414-A414, ISSN: 0012-1797
Rabhi N, Denechaud P-D, Salas E, et al., 2014, The P300/cbp-associated Factor (PCAF) Links ER Stress to β-Cell Function and Insulin Secretion, Publisher: AMER DIABETES ASSOC, Pages: A81-A81, ISSN: 0012-1797
Abdelalim EM, Bonnefond A, Bennaceur-Griscelli A, et al., 2014, Pluripotent Stem Cells as a Potential Tool for Disease Modelling and Cell Therapy in Diabetes, STEM CELL REVIEWS AND REPORTS, Vol: 10, Pages: 327-337, ISSN: 2629-3269
- Author Web Link
- Cite
- Citations: 46
Boardman JP, Walley A, Ball G, et al., 2014, Common Genetic Variants and Risk of Brain Injury After Preterm Birth, PEDIATRICS, Vol: 133, Pages: E1655-E1663, ISSN: 0031-4005
- Author Web Link
- Cite
- Citations: 34
Dimas AS, Lagou V, Barker A, et al., 2014, Impact of Type 2 diabetes susceptibility variants on quantitative glycemic traits reveals mechanistic heterogeneity, Diabetes, Vol: 63, Pages: 2158-2171, ISSN: 0012-1797
Patients with established type 2 diabetes display both β-cell dysfunction and insulin resistance. To define fundamental processes leading to the diabetic state, we examined the relationship between type 2 diabetes risk variants at 37 established susceptibility loci, and indices of proinsulin processing, insulin secretion, and insulin sensitivity. We included data from up to 58,614 nondiabetic subjects with basal measures and 17,327 with dynamic measures. We used additive genetic models with adjustment for sex, age, and BMI, followed by fixed-effects, inverse-variance meta-analyses. Cluster analyses grouped risk loci into five major categories based on their relationship to these continuous glycemic phenotypes. The first cluster (PPARG, KLF14, IRS1, GCKR) was characterized by primary effects on insulin sensitivity. The second cluster (MTNR1B, GCK) featured risk alleles associated with reduced insulin secretion and fasting hyperglycemia. ARAP1 constituted a third cluster characterized by defects in insulin processing. A fourth cluster (TCF7L2, SLC30A8, HHEX/IDE, CDKAL1, CDKN2A/2B) was defined by loci influencing insulin processing and secretion without a detectable change in fasting glucose levels. The final group contained 20 risk loci with no clear-cut associations to continuous glycemic traits. By assembling extensive data on continuous glycemic traits, we have exposed the diverse mechanisms whereby type 2 diabetes risk variants impact disease predisposition.
Langenberg C, Sharp SJ, Franks PW, et al., 2014, Gene-Lifestyle Interaction and Type 2 Diabetes: The EPIC InterAct Case-Cohort Study, PLOS Medicine, Vol: 11, ISSN: 1549-1277
Background: Understanding of the genetic basis of type 2 diabetes (T2D) has progressed rapidly, but the interactionsbetween common genetic variants and lifestyle risk factors have not been systematically investigated in studies withadequate statistical power. Therefore, we aimed to quantify the combined effects of genetic and lifestyle factors on risk ofT2D in order to inform strategies for prevention.Methods and Findings: The InterAct study includes 12,403 incident T2D cases and a representative sub-cohort of 16,154individuals from a cohort of 340,234 European participants with 3.99 million person-years of follow-up. We studied thecombined effects of an additive genetic T2D risk score and modifiable and non-modifiable risk factors using PrenticeweightedCox regression and random effects meta-analysis methods. The effect of the genetic score was significantlygreater in younger individuals (p for interaction = 1.2061024). Relative genetic risk (per standard deviation [4.4 risk alleles])was also larger in participants who were leaner, both in terms of body mass index (p for interaction = 1.5061023) and waistcircumference (p for interaction = 7.4961029). Examination of absolute risks by strata showed the importance of obesity forT2D risk. The 10-y cumulative incidence of T2D rose from 0.25% to 0.89% across extreme quartiles of the genetic score innormal weight individuals, compared to 4.22% to 7.99% in obese individuals. We detected no significant interactionsbetween the genetic score and sex, diabetes family history, physical activity, or dietary habits assessed by a Mediterraneandiet score.Conclusions: The relative effect of a T2D genetic risk score is greater in younger and leaner participants. However, this subgroupis at low absolute risk and would not be a logical target for preventive interventions. The high absolute riskassociated with obesity at any level of genetic risk highlights the importance of universal rather than targeted approachesto lifestyle intervent
Falchi M, El-Sayed Moustafa JS, Takousis P, et al., 2014, Low copy number of the salivary amylase gene predisposes to obesity, Nature Genetics, Vol: 46, Pages: 492-497, ISSN: 1061-4036
Common multi-allelic copy number variants (CNVs) appear enriched for phenotypic associations compared to their biallelic counterparts1,2,3,4. Here we investigated the influence of gene dosage effects on adiposity through a CNV association study of gene expression levels in adipose tissue. We identified significant association of a multi-allelic CNV encompassing the salivary amylase gene (AMY1) with body mass index (BMI) and obesity, and we replicated this finding in 6,200 subjects. Increased AMY1 copy number was positively associated with both amylase gene expression (P = 2.31 × 10−14) and serum enzyme levels (P < 2.20 × 10−16), whereas reduced AMY1 copy number was associated with increased BMI (change in BMI per estimated copy = −0.15 (0.02) kg/m2; P = 6.93 × 10−10) and obesity risk (odds ratio (OR) per estimated copy = 1.19, 95% confidence interval (CI) = 1.13–1.26; P = 1.46 × 10−10). The OR value of 1.19 per copy of AMY1 translates into about an eightfold difference in risk of obesity between subjects in the top (copy number > 9) and bottom (copy number < 4) 10% of the copy number distribution. Our study provides a first genetic link between carbohydrate metabolism and BMI and demonstrates the power of integrated genomic approaches beyond genome-wide association studies.
Winkler TW, Day FR, Croteau-Chonka DC, et al., 2014, Quality control and conduct of genome-wide association meta-analyses, NATURE PROTOCOLS, Vol: 9, Pages: 1192-1212, ISSN: 1754-2189
- Author Web Link
- Cite
- Citations: 270
Svensson P-A, Wahlstrand B, Olsson M, et al., 2014, <i>CDKN2B</i> expression and subcutaneous adipose tissue expandability: Possible influence of the 9p21 atherosclerosis locus, BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, Vol: 446, Pages: 1126-1131, ISSN: 0006-291X
- Author Web Link
- Cite
- Citations: 18
Makki K, Taront S, Molendi-Coste O, et al., 2014, Beneficial Metabolic Effects of Rapamycin Are Associated with Enhanced Regulatory Cells in Diet-Induced Obese Mice, PLOS ONE, Vol: 9, ISSN: 1932-6203
- Author Web Link
- Cite
- Citations: 49
Prokopenko I, Poon W, Maegi R, et al., 2014, A Central Role for GRB10 in Regulation of Islet Function in Man, PLOS Genetics, Vol: 10, ISSN: 1553-7390
Variants in the growth factor receptor-bound protein 10 (GRB10) gene were in a GWAS meta-analysis associated withreduced glucose-stimulated insulin secretion and increased risk of type 2 diabetes (T2D) if inherited from the father, butinexplicably reduced fasting glucose when inherited from the mother. GRB10 is a negative regulator of insulin signaling andimprinted in a parent-of-origin fashion in different tissues. GRB10 knock-down in human pancreatic islets showed reducedinsulin and glucagon secretion, which together with changes in insulin sensitivity may explain the paradoxical reduction ofglucose despite a decrease in insulin secretion. Together, these findings suggest that tissue-specific methylation andpossibly imprinting of GRB10 can influence glucose metabolism and contribute to T2D pathogenesis. The data alsoemphasize the need in genetic studies to consider whether risk alleles are inherited from the mother or the father.
Neve B, Le Bacquer O, Caron S, et al., 2014, Alternative human liver transcripts of TCF7L2 bind to the gluconeogenesis regulator HNF4α at the protein level, DIABETOLOGIA, Vol: 57, Pages: 785-796, ISSN: 0012-186X
- Author Web Link
- Cite
- Citations: 25
Sverrisdottir OO, Timpson A, Toombs J, et al., 2014, Direct Estimates of Natural Selection in Iberia Indicate Calcium Absorption Was Not the Only Driver of Lactase Persistence in Europe, MOLECULAR BIOLOGY AND EVOLUTION, Vol: 31, Pages: 975-983, ISSN: 0737-4038
- Author Web Link
- Cite
- Citations: 37
Saeed S, Bech PR, Hafeez T, et al., 2014, Changes in levels of peripheral hormones controlling appetite are inconsistent with hyperphagia in leptin-deficient subjects, ENDOCRINE, Vol: 45, Pages: 401-408, ISSN: 1355-008X
- Author Web Link
- Cite
- Citations: 14
This data is extracted from the Web of Science and reproduced under a licence from Thomson Reuters. You may not copy or re-distribute this data in whole or in part without the written consent of the Science business of Thomson Reuters.