scholarly journals An Expanded Genome-Wide Association Study of Fructosamine Levels Identifies RCN3 as a Replicating Locus and Implicates FCGRT as the Effector Transcript

2021 ◽  
Author(s):  
Fernando Riveros-Mckay ◽  
David Roberts ◽  
Emanuele Di Angelantonio ◽  
Bing Yu ◽  
Nicole Soranzo ◽  
...  
Keyword(s):  
Association Study ◽  
Genome Wide Association Study ◽  
Genome Wide Association ◽  
European Ancestry ◽  
Diabetes Diagnosis ◽  
Atherosclerosis Risk In Communities ◽  
Functional Studies ◽  
Genome Wide ◽  
Novel Association ◽  
Localization Analysis

Fructosamine is a measure of short-term glycemic control, which has been suggested as a useful complement to glycated hemoglobin (HbA1c) for the diagnosis and monitoring of diabetes. To date, a single genome-wide association study (GWAS) including 8,951 US White and 2,712 US Black individuals without a diabetes diagnosis has been published. Results in Whites and Blacks yielded different association loci, near <i>RCN3</i> and <i>CNTN5</i>, respectively. Here we performed a GWAS on 20,731 European ancestry blood donors, and meta-analysed our results with previous data from US White participants from The Atherosclerosis Risk in Communities (ARIC) study (N<sub>meta</sub>=29,685). We identified a novel association near <i>GCK</i> (rs3757840, beta<sub>meta</sub>=0.0062, MAF=0.49, <i>p<sub>meta</sub></i>=3.66x10<sup>-08</sup>) and confirmed the association near <i>RCN3</i> (rs113886122, beta<sub>meta</sub>=0.0134, MAF=0.17, <i>p<sub>meta</sub></i>= 5.71x10<sup>-18</sup>). Co-localization analysis with whole blood eQTL data suggested <i>FCGRT</i> as the effector transcript at the <i>RCN3</i> locus. We further showed that fructosamine has low heritability (h2=7.7%), has no significant genetic correlation with HbA1c and other glycemic traits in individuals without a diabetes diagnosis (p>0.05), but has evidence of shared genetic etiology with some anthropometric traits (Bonferroni corrected p<0.0012). Our results broaden knowledge of the genetic architecture of fructosamine and prioritize <i>FCGRT </i>for downstream functional studies at<i> </i>the established <i>RCN3</i> locus.

scholarly journals An Expanded Genome-Wide Association Study of Fructosamine Levels Identifies RCN3 as a Replicating Locus and Implicates FCGRT as the Effector Transcript

2021 ◽  
Author(s):  
Fernando Riveros-Mckay ◽  
David Roberts ◽  
Emanuele Di Angelantonio ◽  
Bing Yu ◽  
Nicole Soranzo ◽  
...  
Keyword(s):  
Association Study ◽  
Genome Wide Association Study ◽  
Genome Wide Association ◽  
European Ancestry ◽  
Diabetes Diagnosis ◽  
Atherosclerosis Risk In Communities ◽  
Functional Studies ◽  
Genome Wide ◽  
Novel Association ◽  
Localization Analysis

Fructosamine is a measure of short-term glycemic control, which has been suggested as a useful complement to glycated hemoglobin (HbA1c) for the diagnosis and monitoring of diabetes. To date, a single genome-wide association study (GWAS) including 8,951 US White and 2,712 US Black individuals without a diabetes diagnosis has been published. Results in Whites and Blacks yielded different association loci, near <i>RCN3</i> and <i>CNTN5</i>, respectively. Here we performed a GWAS on 20,731 European ancestry blood donors, and meta-analysed our results with previous data from US White participants from The Atherosclerosis Risk in Communities (ARIC) study (N<sub>meta</sub>=29,685). We identified a novel association near <i>GCK</i> (rs3757840, beta<sub>meta</sub>=0.0062, MAF=0.49, <i>p<sub>meta</sub></i>=3.66x10<sup>-08</sup>) and confirmed the association near <i>RCN3</i> (rs113886122, beta<sub>meta</sub>=0.0134, MAF=0.17, <i>p<sub>meta</sub></i>= 5.71x10<sup>-18</sup>). Co-localization analysis with whole blood eQTL data suggested <i>FCGRT</i> as the effector transcript at the <i>RCN3</i> locus. We further showed that fructosamine has low heritability (h2=7.7%), has no significant genetic correlation with HbA1c and other glycemic traits in individuals without a diabetes diagnosis (p>0.05), but has evidence of shared genetic etiology with some anthropometric traits (Bonferroni corrected p<0.0012). Our results broaden knowledge of the genetic architecture of fructosamine and prioritize <i>FCGRT </i>for downstream functional studies at<i> </i>the established <i>RCN3</i> locus.

scholarly journals Genome-wide Association Study of Pancreatic Fat: The Multiethnic Cohort Adiposity Phenotype Study

2021 ◽  
Author(s):  
Samantha Streicher ◽  
Unhee Lim ◽  
S. Lani Park ◽  
Yuqing Li ◽  
Xin Sheng ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Association Study ◽  
Genome Wide Association Study ◽  
Genome Wide Association ◽  
European Ancestry ◽  
American Population ◽  
Pancreatic Fat ◽  
Genome Wide ◽  
Multiethnic Cohort

Several studies have found associations between higher pancreatic fat content and adverse health outcomes, such as diabetes and the metabolic syndrome, but investigations into the genetic contributions to pancreatic fat are limited.  This genome-wide association study, comprised of 804 participants with MRI-assessed pancreatic fat measurements, was conducted in the ethnically diverse Multiethnic Cohort-Adiposity Phenotype Study (MEC-APS).  Two genetic variants reaching genome-wide significance, rs73449607 on chromosome 13q21.2 (Beta = -0.67, P = 4.50x10 -8 ) and rs7996760 on chromosome 6q14 (Beta = -0.90, P = 4.91x10 -8 ) were associated with percent pancreatic fat on the log scale.  Rs73449607 was most common in the African American population (13%) and rs79967607 was most common in the European American population (6%).  Rs73449607 was also suggestively associated with lower risk of type 2 diabetes (OR = 0.95, 95% CI = 0.89-1.00, P = 0.047) in the Population Architecture Genomics and Epidemiology (PAGE) Study and the DIAbetes Genetics Replication and Meta-analysis (DIAGRAM), which included substantial numbers of non-European ancestry participants (53,102 cases and 193,679 controls).  Rs73449607 is located in an intergenic region between GSX1 and PLUT , and rs79967607 is in intron 1 of EPM2A .  PLUT, a linkRNA, regulates transcription of an adjacent gene, PDX1 , that controls beta-cell function in the mature pancreas, and EPM2A encodes the protein laforin, which plays a critical role in regulating glycogen production.  If validated, these variants may suggest a genetic component for pancreatic fat and a common etiologic link between pancreatic fat and type 2 diabetes.

Abstract 14182: Genome Wide Association Study for High Sensitive Cardiac Troponin T Levels Identifies a Novel Gene in Europeans With Type 1 Diabetes

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Tarunveer S Ahluwalia ◽  
Frederik Persson ◽  
Tine W Hansen ◽  
Lise Tarnow ◽  
Hans-Henrik Parving ◽  
...  
Keyword(s):  
Type 1 Diabetes ◽  
Association Study ◽  
Gene Locus ◽  
Genome Wide Association Study ◽  
Troponin T ◽  
Genome Wide Association ◽  
European Ancestry ◽  
Genome Wide ◽  
Increased Risk

Introduction: Adults with diabetes have a two to four folds increased risk of dying with heart disease compared to those without diabetes. Higher cardiac troponins, especially Troponin T (TnT) is a specific biomarker for cardiac injury also guiding management of chest pain and associated with increased risk of heart failure. Hypothesis: There is limited knowledge on genes regulating cardiac TnT levels. We conducted a genome wide association study (GWAS) for circulating cardiac TnT levels among individuals with type 1 diabetes (T1D). Methods: The study included 849 T1D individuals recruited from the outpatient clinic at Steno Diabetes Center Copenhagen, Denmark. Serum high sensitive TnT (hsTnT) levels were measured and log transformed for normalization after check for outliers (mean ± 4 SD). Genotyping on 538,448 single nucleotide variants (SNVs) was done using Illumina Human Core Exome Chip. After quality control filters: hardy weinberg equilibrium (p >10 -6 ), European ancestry, genotype call rates >95%, common variants were examined in 740 individuals with hs TnT data. We ran linear regression based additive genetic models adjusting for age, sex, diabetes duration and population sub structure using Plink and R statistical programs. P <5 x 10 -8 was genome wide significant (GWS) while 5 x 10 -8 < p < 1 x 10 -6 was considered suggestive. Results: Participants had a mean (SD) age of 43.7 (11.1) years, 57.4% were men, with diabetes duration of 28.0 (9.5) years, HbA1c 8.9 (1.3) % and 50.5% with diabetic nephropathy. Median (IQR) hsTnT levels were 64.7 (29.2-175.6) pg/ml. We identified a GWS missense common variant in the CISD3 gene locus on chromosome 17 (p=1.7 x 10 -8 ) for cardiac hsTnT levels. This gene codes CDGSH Iron Sulfur Domain 3 protein also called Mitochondrial Inner NEET Protein. Two suggestive loci were PTPRD (Protein Tyrosine Phosphatase Receptor Type D; p=4.9 x 10 -7 ) and DCC (DCC Netrin 1 Receptor; 6.6 x 10 -7 ) on chromosomes 9 and 18. PTPRD is a known GWS locus for hsTnT that we reconfirm among T1D individuals. Conclusions: We identify a novel gene locus for circulating cardiac hsTnT levels among T1D individuals of European ancestry. CISD3 is expressed in heart tissue regulating mitochondrial functions. Further validation is suggested.

scholarly journals Genome-wide association study identifies locus at chromosome 2q32.1 associated with syncope and collapse

2019 ◽  
Vol 116 (1) ◽  
pp. 138-148 ◽  
Author(s):  
Katra Hadji-Turdeghal ◽  
Laura Andreasen ◽  
Christian M Hagen ◽  
Gustav Ahlberg ◽  
Jonas Ghouse ◽  
...  
Keyword(s):  
Association Study ◽  
Genome Wide Association Study ◽  
Genome Wide Association ◽  
European Ancestry ◽  
Psychiatric Research ◽  
Carrier Status ◽  
Genome Wide ◽  
Common Genetic Variants ◽  
A Genome ◽  
Significant Locus

Abstract Aims Syncope is a common condition associated with frequent hospitalization or visits to the emergency department. Family aggregation and twin studies have shown that syncope has a heritable component. We investigated whether common genetic variants predispose to syncope and collapse. Methods and results We used genome-wide association data on syncope on 408 961 individuals with European ancestry from the UK Biobank study. In a replication study, we used the Integrative Psychiatric Research Consortium (iPSYCH) cohort (n = 86 189), to investigate the risk of incident syncope stratified by genotype carrier status. We report on a genome-wide significant locus located on chromosome 2q32.1 [odds ratio = 1.13, 95% confidence interval (CI) 1.10–1.17, P = 5.8 × 10−15], with lead single nucleotide polymorphism rs12465214 in proximity to the gene zinc finger protein 804a (ZNF804A). This association was also shown in the iPSYCH cohort, where homozygous carriers of the C allele conferred an increased hazard ratio (1.30, 95% CI 1.15–1.46, P = 1.68 × 10−5) of incident syncope. Quantitative polymerase chain reaction analysis showed ZNF804A to be expressed most abundantly in brain tissue. Conclusion We identified a genome-wide significant locus (rs12465214) associated with syncope and collapse. The association was replicated in an independent cohort. This is the first genome-wide association study to associate a locus with syncope and collapse.

scholarly journals Genome-wide association study of delay discounting in 23,217 adult research participants of European ancestry

2017 ◽  
Vol 21 (1) ◽  
pp. 16-18 ◽  
Author(s):  
Sandra Sanchez-Roige ◽  
◽  
Pierre Fontanillas ◽  
Sarah L. Elson ◽  
Anita Pandit ◽  
...  
Keyword(s):  
Association Study ◽  
Delay Discounting ◽  
Genome Wide Association Study ◽  
Genome Wide Association ◽  
European Ancestry ◽  
Research Participants ◽  
Genome Wide
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