scholarly journals Molecular genetic contributions to self-rated health

2015 ◽  
Author(s):  
Sarah E Harris ◽  
Saskia P Hagenaars ◽  
Gail Davies ◽  
William David Hill ◽  
David CM Liewald ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Genome Wide Association Study ◽  
Uk Biobank ◽  
Psychological Traits ◽  
Self Rated Health ◽  
Genome Wide ◽  
Common Genetic Variants ◽  
A Genome ◽  
Polygenic Scores

Abstract Background Poorer self-rated health (SRH) predicts worse health outcomes, even when adjusted for objective measures of disease at time of rating. Twin studies indicate SRH has a heritability of up to 60% and that its genetic architecture may overlap with that of personality and cognition. Methods We carried out a genome-wide association study (GWAS) of SRH on 111 749 members of the UK Biobank sample. Univariate genome-wide complex trait analysis (GCTA)-GREML analyses were used to estimate the proportion of variance explained by all common autosomal SNPs for SRH. Linkage Disequilibrium (LD) score regression and polygenic risk scoring, two complementary methods, were used to investigate pleiotropy between SRH in UK Biobank and up to 21 health-related and personality and cognitive traits from published GWAS consortia. Results The GWAS identified 13 independent signals associated with SRH, including several in regions previously associated with diseases or disease-related traits. The strongest signal was on chromosome 2 (rs2360675, p = 1.77x10-10) close to KLF7, which has previously been associated with obesity and type 2 diabetes. A second strong peak was identified on chromosome 6 in the major histocompatibility region (rs76380179, p = 6.15x10-10). The proportion of variance in SRH that was explained by all common genetic variants was 13%. Polygenic scores for the following traits and disorders were associated with SRH: cognitive ability, education, neuroticism, BMI, longevity, ADHD, major depressive disorder, schizophrenia, lung function, blood pressure, coronary artery disease, large vessel disease stroke, and type 2 diabetes. Conclusions Individual differences in how people respond to a single item on SRH are partly explained by their genetic propensity to many common psychiatric and physical disorders and psychological traits.

scholarly journals Variants in the FTO and CDKAL1 loci have recessive effects on risk of obesity and type 2 diabetes respectively

2015 ◽  
Author(s):  
Andrew R Wood ◽  
Jessica Tyrell ◽  
Robin Beaumont ◽  
Samuel E Jones ◽  
Marcus A Tuke ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Genome Wide Association Study ◽  
Association Studies ◽  
Genome Wide Association ◽  
Genome Wide Association Studies ◽  
Genome Wide ◽  
Common Genetic Variants ◽  
A Genome ◽  
Recessive Effects

Genome-wide association studies have identified hundreds of common genetic variants associated with obesity and Type 2 diabetes. These studies have focused on additive association tests. Identifying deviations from additivity may provide new biological insights and explain some of the missing heritability for these diseases. To identify non-additive associations we performed a genome-wide association study using a dominance deviation model for BMI, obesity and Type 2 diabetes (4,040 cases) in 120,286 individuals of British ancestry from the UK Biobank study. Known obesity-associated variants in FTO showed strong evidence for deviation from additivity (P=3x10-5) through a recessive effect of the BMI-increasing allele. The average BMI of individuals carrying 0, 1 or 2 BMI-raising alleles was 27.27kg/m2 (95% CI:27.22-27.31), 27.54kg/m2 (95% CI:27.50-27.58), and 28.07kg/m2 (95% CI:28.0-28.14), respectively. A similar effect was observed in 105,643 individuals from the GIANT consortium (P=0.003; Pmeta-analysis=1x10-7). We also detected a recessive effect (Pdomdev=5x10-4) at CDKAL1 for Type 2 diabetes risk. Homozygous risk allele carriers had an OR=1.48 (95% CI:1.32-1.65) in comparison to the heterozygous group that had an OR=1.06 (95% CI:0.99-1.14), a result consistent with a previous study. We did not identify any novel genome-wide associations. In conclusion, although we find no evidence for widespread non-additive effects contributing to the genetic risk of obesity and Type 2 diabetes, we find robust examples of recessive effects at the FTO and CDKAL1 loci.

scholarly journals A Genome-Wide Association Study of Type 2 Diabetes in Finns Detects Multiple Susceptibility Variants

Science ◽  
2007 ◽  
Vol 316 (5829) ◽  
pp. 1341-1345 ◽  
Author(s):  
L. J. Scott ◽  
K. L. Mohlke ◽  
L. L. Bonnycastle ◽  
C. J. Willer ◽  
Y. Li ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Association Study ◽  
Genome Wide Association Study ◽  
Genome Wide Association ◽  
Genome Wide ◽  
A Genome

scholarly journals A Genome-Wide Association Study of Diabetic Kidney Disease in Subjects With Type 2 Diabetes

Diabetes ◽  
2018 ◽  
Vol 67 (7) ◽  
pp. 1414-1427 ◽  
Author(s):  
Natalie R. van Zuydam ◽  
Emma Ahlqvist ◽  
Niina Sandholm ◽  
Harshal Deshmukh ◽  
N. William Rayner ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Kidney Disease ◽  
Association Study ◽  
Diabetic Kidney Disease ◽  
Genome Wide Association Study ◽  
Genome Wide Association ◽  
Diabetic Kidney ◽  
Genome Wide ◽  
A Genome

scholarly journals A Genome-Wide Association Study Confirms Previously Reported Loci for Type 2 Diabetes in Han Chinese

PLoS ONE ◽  
2011 ◽  
Vol 6 (7) ◽  
pp. e22353 ◽  
Author(s):  
Bin Cui ◽  
Xiaolin Zhu ◽  
Min Xu ◽  
Ting Guo ◽  
Dalong Zhu ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Association Study ◽  
Genome Wide Association Study ◽  
Han Chinese ◽  
Genome Wide Association ◽  
Genome Wide ◽  
A Genome

scholarly journals Pharmacogenetics of Oral Antidiabetic Drugs

2013 ◽  
Vol 2013 ◽  
pp. 1-10 ◽  
Author(s):  
Matthijs L. Becker ◽  
Ewan R. Pearson ◽  
Ivan Tkáč
Keyword(s):  
Type 2 Diabetes ◽  
Genome Wide Association Study ◽  
Antidiabetic Drugs ◽  
Gene Variants ◽  
Oral Antidiabetic Drugs ◽  
Oral Antidiabetic ◽  
Genome Wide ◽  
A Genome ◽  
Register Studies

Oral antidiabetic drugs (OADs) are used for more than a half-century in the treatment of type 2 diabetes. Only in the last five years, intensive research has been conducted in the pharmacogenetics of these drugs based mainly on the retrospective register studies, but only a handful of associations detected in these studies were replicated. The gene variants inCYP2C9,ABCC8/KCNJ11, andTCF7L2were associated with the effect of sulfonylureas.CYP2C9encodes sulfonylurea metabolizing cytochrome P450 isoenzyme 2C9,ABCC8andKCNJ11genes encode proteins constituting ATP-sensitive K+channel which is a therapeutic target for sulfonylureas, andTCF7L2is a gene with the strongest association with type 2 diabetes.SLC22A1,SLC47A1, andATMgene variants were repeatedly associated with the response to metformin.SLC22A1andSLC47A1encode metformin transporters OCT1 and MATE1, respectively. The function of a gene variant nearATMgene identified by a genome-wide association study is not elucidated so far. The first variant associated with the response to gliptins is a polymorphism in the proximity ofCTRB1/2gene which encodes chymotrypsinogen. Establishment of diabetes pharmacogenetics consortia and reduction in costs of genomics might lead to some significant clinical breakthroughs in this field in a near future.

scholarly journals A Genome-Wide Association Study IdentifiesGRK5andRASGRP1as Type 2 Diabetes Loci in Chinese Hans

Diabetes ◽  
2012 ◽  
Vol 62 (1) ◽  
pp. 291-298 ◽  
Author(s):  
Huaixing Li ◽  
Wei Gan ◽  
Ling Lu ◽  
Xiao Dong ◽  
Xueyao Han ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Association Study ◽  
Genome Wide Association Study ◽  
Genome Wide Association ◽  
Genome Wide ◽  
A Genome

scholarly journals Genome-Wide Association Study of lipid traits in youth with type 2 diabetes

2021 ◽  
Author(s):  
Nicola Santoro ◽  
Ling Chen ◽  
Jennifer Todd ◽  
Jasmin Divers ◽  
Amy S Shah ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Association Study ◽  
Genome Wide Association Study ◽  
Risk Allele ◽  
Density Lipoprotein ◽  
Genome Wide Association ◽  
Relationship Matrix ◽  
Genome Wide ◽  
A Genome

Abstract Context Dyslipidemia is highly prevalent in youth with type 2 diabetes (T2D), yet the pathogenic components of dyslipidemia in youth with T2D are poorly understood. Objective To evaluate the genetic determinants of lipid traits in youth with T2D through a genome-wide association study (GWAS). Design, participants and main outcome measures We genotyped 206,928 variants and imputed 17,642,824 variants in 1,076 youth (mean age 15.0 ±2.48 years) with T2D from the Treatment Options for Type 2 Diabetes in Adolescents and Youth (TODAY) and SEARCH for Diabetes in Youth (SEARCH) studies as part of the Progress in Diabetes Genetics in Youth (ProDiGY) consortium. We performed association testing for triglyceride, low-density lipoprotein (LDL-c) and high-density lipoprotein (HDL-c) concentrations adjusted for the genetic relationship matrix within each sub-study followed by meta-analyses for each trait. Results We identified a novel association between a deletion on chromosome 3 (3:67817380_AT/A_Deletion:RP11-81N13.1) and triglyceride levels at genome-wide level of significance (P=2.3×10 -8) with each risk allele increasing triglycerides by 20%. We also identified a genome-wide significant signal at rs247617 (P=5.1×10 -9) between HERFUD1 and CETP associated with HDL-c, with carriers of one copy of the risk allele having twice higher HDL-c. Conclusions Our genetic analyses of lipid traits in youth with T2D have identified one novel and one previously known locus. Additional studies are needed to further characterize the genetic architecture of dyslipidemia in youth with T2D.

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