scholarly journals The UGT2A1/UGT2A2 locus is associated with COVID-19-related anosmia

2021 ◽  
Author(s):  
Janie F. Shelton ◽  
Anjali J. Shastri ◽  
Stella Aslibekyan ◽  
Adam Auton ◽  
Keyword(s):  
Genome Wide Association Study ◽  
Genome Wide Association ◽  
European Ancestry ◽  
P Value ◽  
Biological Mechanisms ◽  
Genome Wide ◽  
Characteristic Symptom ◽  
Demographic Patterns ◽  
Test Result ◽  
Shed Light

Loss of sense of smell is a characteristic symptom of infection with SARS-CoV-2. However, specific mechanisms linking infection with loss of smell are poorly understood. Using self-reported symptom data from the 23andMe COVID-19 study, we describe the demographic patterns associated with COVID-19 related anosmia, and find the symptom is more often reported in women and younger respondents, and less often by those of East Asian and African American ancestry compared to those of European ancestry. We ran a trans-ethnic genome-wide association study (GWAS) comparing loss of smell or taste (n=47,298) with no loss of smell or taste (n=22,543) among those with a positive SARS-CoV-2 test result. We identified an association (rs7688383) in the vicinity of the UGT2A1 and UGT2A2 genes (OR=1.115, p-value=4x10-15), which have been linked to olfactory function. These results may shed light on the biological mechanisms underlying COVID-19 related anosmia.

scholarly journals Genome-Wide Association Study Identifies Loci Associated with Sensitive Skin

Cosmetics ◽  
2020 ◽  
Vol 7 (2) ◽  
pp. 49
Author(s):  
Miranda A. Farage ◽  
Yunxuan Jiang ◽  
Jay P. Tiesman ◽  
Pierre Fontanillas ◽  
Rosemarie Osborne
Keyword(s):  
Genome Wide Association Study ◽  
Association Studies ◽  
Genome Wide Association ◽  
European Ancestry ◽  
P Value ◽  
Genome Wide Association Studies ◽  
Online Questionnaire ◽  
Sensitive Skin ◽  
Genome Wide ◽  
Skin Conditions

Individuals suffering from sensitive skin often have other skin conditions and/or diseases, such as fair skin, freckles, rosacea, or atopic dermatitis. Genome-wide association studies (GWAS) have been performed for some of these conditions, but not for sensitive skin. In this study, a total of 23,426 unrelated participants of European ancestry from the 23andMe database were evaluated for self-declared sensitive skin, other skin conditions, and diseases using an online questionnaire format. Responders were separated into two groups: those who declared they had sensitive skin (n = 8971) and those who declared their skin was not sensitive (controls, n = 14,455). A GWAS of sensitive skin individuals identified three genome-wide significance loci (p-value < 5 × 10−8) and seven suggestive loci (p-value < 1 × 10−6). Of the three most significant loci, all have been associated with pigmentation and two have been associated with acne.

scholarly journals Assessment of rosacea symptom severity by genome-wide association study and expression analysis highlights immuno-inflammatory and skin pigmentation genes

2018 ◽  
Vol 27 (15) ◽  
pp. 2762-2772 ◽  
Author(s):  
Jennifer L Aponte ◽  
Mathias N Chiano ◽  
Laura M Yerges-Armstrong ◽  
David A Hinds ◽  
Chao Tian ◽  
...  
Keyword(s):  
Association Study ◽  
Symptom Severity ◽  
Genome Wide Association Study ◽  
Skin Pigmentation ◽  
Genome Wide Association ◽  
European Ancestry ◽  
P Value ◽  
Significance Level ◽  
Genome Wide ◽  
A Genome

Abstract Rosacea is a common, chronic skin disease of variable severity with limited treatment options. The cause of rosacea is unknown, but it is believed to be due to a combination of hereditary and environmental factors. Little is known about the genetics of the disease. We performed a genome-wide association study (GWAS) of rosacea symptom severity with data from 73 265 research participants of European ancestry from the 23andMe customer base. Seven loci had variants associated with rosacea at the genome-wide significance level (P < 5 × 10−8). Further analyses highlighted likely gene regions or effector genes including IRF4 (P = 1.5 × 10−17), a human leukocyte antigen (HLA) region flanked by PSMB9 and HLA-DMB (P = 2.2 × 10−15), HERC2-OCA2 (P = 4.2 × 10−12), SLC45A2 (P = 1.7 × 10−10), IL13 (P = 2.8 × 10−9), a region flanked by NRXN3 and DIO2 (P = 4.1 × 10−9), and a region flanked by OVOL1and SNX32 (P = 1.2 × 10−8). All associations with rosacea were novel except for the HLA locus. Two of these loci (HERC-OCA2 and SLC45A2) and another precedented variant (rs1805007 in melanocortin 1 receptor) with an association P value just below the significance threshold (P = 1.3 × 10−7) have been previously associated with skin phenotypes and pigmentation, two of these loci are linked to immuno-inflammation phenotypes (IL13 and PSMB9-HLA-DMA) and one has been associated with both categories (IRF4). Genes within three loci (PSMB9-HLA-DMA, HERC-OCA2 and NRX3-DIO2) were differentially expressed in a previously published clinical rosacea transcriptomics study that compared lesional to non-lesional samples. The identified loci provide specificity of inflammatory mechanisms in rosacea, and identify potential pathways for therapeutic intervention.

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

scholarly journals Genome-wide association studies on endometriosis and endometriosis-related infertility

2018 ◽  
Author(s):  
Geneviève Galarneau ◽  
Pierre Fontanillas ◽  
Caterina Clementi ◽  
Tina Hu-Seliger ◽  
David-Emlyn Parfitt ◽  
...  
Keyword(s):  
Genome Wide Association Study ◽  
Association Studies ◽  
Reproductive Age ◽  
Genome Wide Association ◽  
European Ancestry ◽  
Model Organisms ◽  
Genome Wide Association Studies ◽  
Gwas Study ◽  
Genome Wide ◽  
Genome Wide Significance

AbstractEndometriosis affects ∼10% of women of reproductive age. It is characterized by the growth of endometrial-like tissue outside the uterus and is frequently associated with severe pain and infertility. We performed the largest endometriosis genome-wide association study (GWAS) to date, with 37,183 cases and 251,258 controls. All women were of European ancestry. We also performed the first GWAS of endometriosis-related infertility, including 2,969 cases and 3,770 controls. Our endometriosis GWAS study replicated, at genome-wide significance, seven loci identified in previous endometriosis GWASs (CELA3A-CDC42, SYNE1, KDR, FSHB-ARL14EP, GREB1, ID4, and CEP112) and identified seven new candidate loci with genome-wide significance (NGF, ATP1B1-F5, CD109, HEY2, OSR2-VPS13B, WT1, and TEX11-SLC7A3). No loci demonstrated genome-wide significance for endometriosis-related infertility, however, the three most strongly associated loci (MCTP1, EPS8L3-CSF1, and LPIN1) were in or near genes associated with female fertility or embryonic lethality in model organisms. These results reveal new candidate genes with potential involvement in the pathophysiology of endometriosis and endometriosis-related infertility.

scholarly journals Genome-wide association study of susceptibility to hospitalised respiratory infections

2021 ◽  
Vol 6 ◽  
pp. 290
Author(s):  
Alexander T. Williams ◽  
Nick Shrine ◽  
Hardeep Naghra-van Gijzel ◽  
Joanna C. Betts ◽  
Edith M. Hessel ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Association Study ◽  
Respiratory Infection ◽  
Genome Wide Association Study ◽  
Respiratory Infections ◽  
Genome Wide Association ◽  
Uk Biobank ◽  
Biological Mechanisms ◽  
Genome Wide ◽  
Infection Susceptibility

Background: Globally, respiratory infections contribute to significant morbidity and mortality. However, genetic determinants of respiratory infections are understudied and remain poorly understood. Methods: We conducted a genome-wide association study in 19,459 hospitalised respiratory infection cases and 101,438 controls from UK Biobank. We followed-up well-imputed top signals from the UK Biobank discovery analysis in 50,912 respiratory infection cases and 150,442 controls from 11 cohorts. We aggregated effect estimates across studies using inverse variance-weighted meta-analyses. Additionally, we investigated the function of the top signals in order to gain understanding of the underlying biological mechanisms. Results: In the discovery analysis, we report 56 signals at P<5×10-6, one of which was genome-wide significant (P<5×10-8). The genome-wide significant signal was in an intron of PBX3, a gene that encodes pre-B-cell leukaemia transcription factor 3, a homeodomain-containing transcription factor. Further, the genome-wide significant signal was found to colocalise with gene-specific expression quantitative trait loci (eQTLs) affecting expression of PBX3 in lung tissue, where the respiratory infection risk alleles were associated with decreased PBX3 expression in lung tissue, highlighting a possible biological mechanism. Of the 56 signals, 40 were well-imputed in UK Biobank and were investigated in the 11 follow-up cohorts. None of the 40 signals replicated, with effect estimates attenuated. Conclusions: Our discovery analysis implicated PBX3 as a candidate causal gene and suggests a possible role of transcription factor binding activity in respiratory infection susceptibility. However, the PBX3 signal, and the other well-imputed signals, did not replicate when aggregating effect estimates across 11 independent cohorts. Significant phenotypic heterogeneity and differences in study ascertainment may have contributed to this lack of statistical replication. Overall, our study highlighted putative associations and possible biological mechanisms that may provide insight into respiratory infection susceptibility.

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