scholarly journals Genome-wide association study of self-reported walking pace suggests beneficial effects of brisk walking on health and survival

2020 ◽  
Vol 3 (1) ◽  
Author(s):  
Iain R. Timmins ◽  
Francesco Zaccardi ◽  
Christopher P. Nelson ◽  
Paul W. Franks ◽  
Thomas Yates ◽  
...  
Keyword(s):  
Association Study ◽  
Genome Wide Association Study ◽  
Strong Predictor ◽  
Genetic Correlations ◽  
Causal Link ◽  
Genome Wide Association ◽  
European Ancestry ◽  
Beneficial Effects ◽  
Genome Wide ◽  
A Genome

AbstractWalking is a simple form of exercise, widely promoted for its health benefits. Self-reported walking pace has been associated with a range of cardiorespiratory and cancer outcomes, and is a strong predictor of mortality. Here we perform a genome-wide association study of self-reported walking pace in 450,967 European ancestry UK Biobank participants. We identify 70 independent associated loci (P < 5 × 10−8), 11 of which are novel. We estimate the SNP-based heritability as 13.2% (s.e. = 0.21%), reducing to 8.9% (s.e. = 0.17%) with adjustment for body mass index. Significant genetic correlations are observed with cardiometabolic, respiratory and psychiatric traits, educational attainment and all-cause mortality. Mendelian randomization analyses suggest a potential causal link of increasing walking pace with a lower cardiometabolic risk profile. Given its low heritability and simple measurement, these findings suggest that self-reported walking pace is a pragmatic target for interventions aiming for general benefits on health.

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.

Abstract 051: Genome-wide Association Study Identifies 12 Loci for Habitual Consumption of Bitter and Sweet Beverages

Circulation ◽  
2018 ◽  
Vol 137 (suppl_1) ◽  
Author(s):  
Victor W Zhong ◽  
Sandra Sanchez-Roige ◽  
Peter Kraft ◽  
Rob M Van Dam ◽  
Daniel I Chasman ◽  
...  
Keyword(s):  
Chronic Disease ◽  
Association Study ◽  
Genome Wide Association Study ◽  
Genetic Model ◽  
Taste Perception ◽  
Genome Wide Association ◽  
European Ancestry ◽  
Multiple Snps ◽  
Genome Wide ◽  
A Genome

Introduction: Widely consumed beverages (e.g., soft drinks, coffee, tea) are critical sources of energy, added sugar and phytochemicals and are associated with obesity and chronic disease. Taste perception and preferences are highly heritable and strong determinants of food and beverage choice. We aimed to identify novel loci underlying habitual bitter and sweet beverage intake. Methods: We performed a genome-wide association study (GWAS) of self-reported bitter and sweet beverage intake in participants of European ancestry in the UK Biobank. Diet was assessed via multiple 24-h diet recalls (n=84703, subset) or questionnaire (n=335909, all). Bitter beverage intake was the sum of coffee, tea and grapefruit juice. Sweet beverage intake was the sum of artificially and sugar sweetened beverages and other fruit juice. Multivariable linear regression under an additive genetic model was applied. GW-significant (P < 5х10 -8 ) SNPs were followed-up for replication in independent studies of European ancestry. Results: Multiple SNPs spanning 11 loci were associated with bitter beverage intake (P <5х10 -8 , Table 1), and at least 5 of them reflected the caffeine content of coffee and tea. Multiple SNPs in the obesity candidate gene FTO were associated with sweet beverage intake (P <5х10 -8 ). The effect size per allele ranged from 0.02 to 0.2 cup per day. Loci in/near AHR, CYP1A2, and FTO were associated with both bitter and sweet beverage intake but in opposite directions. Replication efforts are ongoing. So far, associations at all loci, except 1q25.2 and 2q36.2, were replicated (P range: 0.04 to 1.8x10 -8 ) in independent studies (n=17322) which provided 80% power for replicating 8 of these 12 loci at P=0.05. Conclusions: Loci linked to caffeine metabolism and obesity predisposition rather than taste are major determinants of beverage intake. These and other identified loci have been linked to chronic disease and risk factors, suggesting causal or pleiotropic effects. Our findings have potential public health and methodological implications.

scholarly journals THU0464 A genome-wide association study of gout in people of european ancestry

2017 ◽  
Author(s):  
TR Merriman ◽  
M Cadzow ◽  
M Merriman ◽  
A Phipps-Green ◽  
R Topless ◽  
...  
Keyword(s):  
Association Study ◽  
Genome Wide Association Study ◽  
Genome Wide Association ◽  
European Ancestry ◽  
Genome Wide ◽  
A Genome

A genome-wide association study of depressive symptoms in women of European ancestry

2010 ◽  
Vol 51 (6) ◽  
pp. e3
Author(s):  
M.C. Cornelis ◽  
J. Agnew-Blais ◽  
P. Kraft ◽  
D. Hunter ◽  
M. Jensen ◽  
...  
Keyword(s):  
Depressive Symptoms ◽  
Association Study ◽  
Genome Wide Association Study ◽  
Genome Wide Association ◽  
European Ancestry ◽  
Genome Wide ◽  
A Genome

scholarly journals Genome-wide association study identifies RNF123 locus as associated with chronic widespread musculoskeletal pain

2021 ◽  
pp. annrheumdis-2020-219624
Author(s):  
Md Shafiqur Rahman ◽  
Bendik S Winsvold ◽  
Sergio O Chavez Chavez ◽  
Sigrid Børte ◽  
Yakov A Tsepilov ◽  
...  
Keyword(s):  
Association Study ◽  
Musculoskeletal Pain ◽  
Tissue Specificity ◽  
Genome Wide Association Study ◽  
Genetic Correlations ◽  
The Body ◽  
Genome Wide Association ◽  
Suggestive Association ◽  
Genome Wide ◽  
A Genome

Background and objectivesChronic widespread musculoskeletal pain (CWP) is a symptom of fibromyalgia and a complex trait with poorly understood pathogenesis. CWP is heritable (48%–54%), but its genetic architecture is unknown and candidate gene studies have produced inconsistent results. We conducted a genome-wide association study to get insight into the genetic background of CWP.MethodsNorthern Europeans from UK Biobank comprising 6914 cases reporting pain all over the body lasting >3 months and 242 929 controls were studied. Replication of three independent genome-wide significant single nucleotide polymorphisms was attempted in six independent European cohorts (n=43 080; cases=14 177). Genetic correlations with risk factors, tissue specificity and colocalisation were examined.ResultsThree genome-wide significant loci were identified (rs1491985, rs10490825, rs165599) residing within the genes Ring Finger Protein 123 (RNF123), ATPase secretory pathway Ca2+transporting 1 (ATP2C1) and catechol-O-methyltransferase (COMT). The RNF123 locus was replicated (meta-analysis p=0.0002), the ATP2C1 locus showed suggestive association (p=0.0227) and the COMT locus was not replicated. Partial genetic correlation between CWP and depressive symptoms, body mass index, age of first birth and years of schooling were identified. Tissue specificity and colocalisation analysis highlight the relevance of skeletal muscle in CWP.ConclusionsWe report a novel association of RNF123 locus and a suggestive association of ATP2C1 locus with CWP. Both loci are consistent with a role of calcium regulation in CWP. The association with COMT, one of the most studied genes in chronic pain field, was not confirmed in the replication analysis.

scholarly journals Multiethnic genome-wide association study of differentiated thyroid cancer in the EPITHYR consortium

2020 ◽  
Author(s):  
Therese TRUONG ◽  
Fabienne Lesueur ◽  
Pierre-emmanuel Sugier ◽  
Julie Guibon ◽  
Constance Xhaard ◽  
...  
Keyword(s):  
Association Study ◽  
Genome Wide Association Study ◽  
Differentiated Thyroid Carcinoma ◽  
Incidence Rates ◽  
Genome Wide Association ◽  
European Ancestry ◽  
Risk Alleles ◽  
Genome Wide ◽  
A Genome ◽  
High Incidence

Incidence of differentiated thyroid carcinoma (DTC) varies considerably between ethnic groups, with particularly high incidence rates in Pacific Islanders. Here, we conducted a genome-wide association study (GWAS) involving 1,554 cases/1,973 controls of European ancestry and 301 cases/348 controls of Oceanian ancestry from the EPITHYR consortium. Our results confirmed the association with the known DTC susceptibility loci at 2q35, 8p12, 9q22.33 and 14q13.3 in the European ancestry population and suggested two novel signals at 1p31.3 (rs334729) and 16q23.2 (rs16950982), which were associated with TSH levels in previous GWAS. We additionally replicated an association with 5p15.33 reported previously in Chinese and European populations. Except at 1p31.3, all associations were in the same direction in the population of Oceanian ancestry. The frequency of risk alleles at 2q35, 5p15.33 and 16q23.2 were significantly higher in Oceanians than in Europeans and may explain part of the highest DTC incidence observed in Oceanians.

scholarly journals Genome-wide association study of problematic opioid prescription use in 132,113 23andMe research participants of European ancestry

2021 ◽  
Author(s):  
Sandra Sanchez-Roige ◽  
Pierre Fontanillas ◽  
Mariela V. Jennings ◽  
Sevim B. Bianchi ◽  
Yuye Huang ◽  
...  
Keyword(s):  
Association Study ◽  
Risk Taking ◽  
Genetic Basis ◽  
Genome Wide Association Study ◽  
Genetic Correlations ◽  
Genome Wide Association ◽  
European Ancestry ◽  
Opioid Use ◽  
Research Participants ◽  
Genome Wide

AbstractThe growing prevalence of opioid use disorder (OUD) constitutes an urgent health crisis. Ample evidence indicates that risk for OUD is heritable. As a surrogate (or proxy) for OUD, we explored the genetic basis of using prescription opioids ‘not as prescribed’. We hypothesized that misuse of opiates might be a heritable risk factor for OUD. To test this hypothesis, we performed a genome-wide association study (GWAS) of problematic opioid use (POU) in 23andMe research participants of European ancestry (N = 132,113; 21% cases). We identified two genome-wide significant loci (rs3791033, an intronic variant of KDM4A; rs640561, an intergenic variant near LRRIQ3). POU showed positive genetic correlations with the two largest available GWAS of OUD and opioid dependence (rg = 0.64, 0.80, respectively). We also identified numerous additional genetic correlations with POU, including alcohol dependence (rg = 0.74), smoking initiation (rg = 0.63), pain relief medication intake (rg = 0.49), major depressive disorder (rg = 0.44), chronic pain (rg = 0.42), insomnia (rg = 0.39), and loneliness (rg = 0.28). Although POU was positively genetically correlated with risk-taking (rg = 0.38), conditioning POU on risk-taking did not substantially alter the magnitude or direction of these genetic correlations, suggesting that POU does not simply reflect a genetic tendency towards risky behavior. Lastly, we performed phenome- and lab-wide association analyses, which uncovered additional phenotypes that were associated with POU, including respiratory failure, insomnia, ischemic heart disease, and metabolic and blood-related biomarkers. We conclude that opioid misuse can be measured in population-based cohorts and provides a cost-effective complementary strategy for understanding the genetic basis of OUD.

scholarly journals Genome-wide association study of problematic opioid prescription use in 132,113 23andMe research participants of European ancestry

2021 ◽  
Author(s):  
Sandra Sanchez-Roige ◽  
Pierre Fontanillas ◽  
Mariela V Jennings ◽  
Sevim Bianchi ◽  
Yuye Huang ◽  
...  
Keyword(s):  
Association Study ◽  
Risk Taking ◽  
Genetic Basis ◽  
Genome Wide Association Study ◽  
Genetic Correlations ◽  
Genome Wide Association ◽  
European Ancestry ◽  
Opioid Use ◽  
Research Participants ◽  
Genome Wide

Rates of opioid use disorder (OUD) constitute an urgent health crisis. Ample evidence indicates that risk for OUD is heritable. As a surrogate (or proxy) for OUD, we explored the genetic basis of using opioids "not as prescribed". We hypothesized that misuse of opiates might be a heritable risk factor for OUD. To test this hypothesis, we performed a genome-wide association study (GWAS) of problematic opioid use (POU; "ever taking opioid prescriptions not as prescribed") in 132,113 23andMe research participants of European ancestry (Ncases=27,805). Our GWAS identified two genome-wide significant loci (rs3791033, an intronic variant of KDM4A; rs640561, an intergenic variant near LRRIQ3). POU showed a positive genetic correlation with opioid dependence and OUD, as measured in the largest available GWAS (rg=0.57-0.80). We also identified numerous additional genetic correlations with POU, including alcohol dependence (rg=0.74), smoking initiation (rg=0.63), pain relief medication intake (rg=0.49), major depressive disorder (rg=0.44), chronic pain (rg=0.42), insomnia (rg=0.39), and loneliness (rg=0.28). Although POU was positively genetically correlated with risk-taking (rg=0.38), conditioning POU on risk-taking did not substantially alter the magnitude or direction of these genetic correlations, suggesting that POU does not simply reflect a general tendency for risky behavior. We conclude that opioid misuse can be measured in population-based cohorts and provides a cost-effective complementary strategy for understanding the genetic basis of OUD.

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