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.

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 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 study reveals sex-specific genetic architecture of facial attractiveness

2018 ◽  
Author(s):  
Bowen Hu ◽  
Ning Shen ◽  
James J. Li ◽  
Hyunseung Kang ◽  
Jinkuk Hong ◽  
...  
Keyword(s):  
Association Study ◽  
Genetic Architecture ◽  
Genetic Basis ◽  
Genome Wide Association Study ◽  
Genetic Correlations ◽  
Facial Attractiveness ◽  
Genome Wide Association ◽  
Hormone Synthesis ◽  
Genome Wide ◽  
A Genome

AbstractFacial attractiveness is a complex human trait of great interest in both academia and industry. Literature on sociological and phenotypic factors associated with facial attractiveness is rich, but its genetic basis is poorly understood. In this paper, we conducted a genome-wide association study to discover genetic variants associated with facial attractiveness using 3,928 samples in the Wisconsin Longitudinal Study. We identified two genome-wide significant loci and highlighted a handful of candidate genes, many of which are specifically expressed in human tissues involved in reproduction and hormone synthesis. Additionally, facial attractiveness showed strong and negative genetic correlations with BMI in females and with blood lipids in males. Our analysis also suggested sex-specific selection pressure on variants associated with lower male attractiveness. These results revealed sex-specific genetic architecture of facial attractiveness and provided fundamental new insights into its genetic basis.

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

2017 ◽  
Author(s):  
Sandra Sanchez-Roige ◽  
Pierre Fontanillas ◽  
Sarah L. Elson ◽  
Anita Pandit ◽  
Ellen M. Schmidt ◽  
...  
Keyword(s):  
Body Weight ◽  
Association Study ◽  
Delay Discounting ◽  
Genome Wide Association Study ◽  
Genome Wide Association ◽  
European Ancestry ◽  
Research Participants ◽  
Hyperactivity Disorder ◽  
Genome Wide ◽  
A Genome

ABSTRACTDelay discounting (DD), which is the tendency to discount the value of delayed versus current rewards, is elevated in a constellation of diseases and behavioral conditions. We performed a genome-wide association study of DD using 23,127 research participants of European ancestry. The most significantly associated SNP was rs6528024 (P = 2.40 × 10−8), which is located in an intron of the gene GPM6B. We also showed that 12% of the variance in DD was accounted for by genotype, and that the genetic signature of DD overlapped with attention-deficit/hyperactivity disorder, schizophrenia, major depression, smoking, personality, cognition, and body weight.

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 of Opioid Cessation

2020 ◽  
Vol 9 (1) ◽  
pp. 180 ◽  
Author(s):  
Jiayi W. Cox ◽  
Richard M. Sherva ◽  
Kathryn L. Lunetta ◽  
Emma C. Johnson ◽  
Nicholas G. Martin ◽  
...  
Keyword(s):  
Association Study ◽  
Genome Wide Association Study ◽  
Chronic Back Pain ◽  
The United States ◽  
Genome Wide Association ◽  
European Ancestry ◽  
Risk Scores ◽  
Opioid Use ◽  
Genome Wide ◽  
A Genome

The United States is experiencing an epidemic of opioid use disorder (OUD) and overdose-related deaths. However, the genetic basis for the ability to discontinue opioid use has not been investigated. We performed a genome-wide association study (GWAS) of opioid cessation (defined as abstinence from illicit opioids for >1 year or <6 months before the interview date) in 1130 African American (AA) and 2919 European ancestry (EA) participants recruited for genetic studies of substance use disorders and who met lifetime Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM-5) criteria for OUD. Association tests performed separately within each ethnic group were combined by meta-analysis with results obtained from the Comorbidity and Trauma Study. Although there were no genome-wide significant associations, we found suggestive associations with nine independent loci, including three which are biologically relevant: rs4740988 in PTPRD (pAA + EA = 2.24 × 10−6), rs36098404 in MYOM2 (pEA = 2.24 × 10−6), and rs592026 in SNAP25-AS1 (pEA = 6.53 × 10−6). Significant pathways identified in persons of European ancestry (EA) are related to vitamin D metabolism (p = 3.79 × 10−2) and fibroblast growth factor (FGF) signaling (p = 2.39 × 10−2). UK Biobank traits including smoking and drinking cessation and chronic back pain were significantly associated with opioid cessation using GWAS-derived polygenic risk scores. These results provide evidence for genetic influences on opioid cessation, suggest genetic overlap with other relevant traits, and may indicate potential novel therapeutic targets for OUD.

scholarly journals Genome-Wide Association Study (GWAS) For Cold Tolerance at The Bud Burst Stage in Rice Using SNP Markers

2021 ◽  
Author(s):  
Caijing Li ◽  
Jindong Liu ◽  
Jianxin Bian ◽  
Tao Jin ◽  
Baoli Zou ◽  
...  
Keyword(s):  
Low Temperature ◽  
Association Study ◽  
Cold Tolerance ◽  
Genetic Basis ◽  
Genome Wide Association Study ◽  
Genome Wide Association ◽  
Bud Burst ◽  
Rice Varieties ◽  
Rice Landraces ◽  
Genome Wide

Abstract Background: Rice is a crop that is very sensitive to low temperature, and its morphological development and production are greatly affected by low temperature. Therefore, understanding the genetic basis of cold tolerance in rice is of great significance for mining favorable genes and cultivating excellent rice varieties. However, there were limited studies focusing on cold tolerance at the bud burst stage, therefore, considerable attention should be paid to the genetic basis of cold tolerance at the bud burst stage (CTBB).Results: In this study, a natural population consisting of 211 rice landraces collected from 15 provinces of China and other countries were firstly used to evaluate the cold tolerance at the bud burst stage. Population structure analysis showed that this population divided into three groups and was rich in genetic diversity. Our evaluation results confered that the japonica rice was more tolerance to cold at the bud burst stage than indica rice. Genome-wide association study (GWAS) were performed through the phenotypic data of 211 rice landraces and 36,727 SNPs dataset under a mixed linear model, and 12 QTLs (P < 0.0001) were identified according to the seedling survival rate (SSR) treated at 4 ℃, in which there are five QTLs (qSSR2-2, qSSR3-1, qSSR3-2, qSSR3-3 and qSSR9) which were co-located with previous studies, and seven QTLs (qSSR2-1, qSSR3-4, qSSR3-5, qSSR3-6, qSSR3-7, qSSR4 and qSSR7) which were reported for the first time. Among these QTLs, qSSR9, harboring the highest-peak SNP, explained biggest phenotypic variation. Through bioinformatics analysis, five genes (LOC_Os09g12440, LOC_Os09g12470, LOC_Os09g12520, LOC_Os09g12580 and LOC_Os09g12720) were nominated as candidates for qSSR9. Conclusion: This natural population consisting of 211 rice landraces with high density SNPs will serve as a better choice for identifying rice QTLs/genes in future, and the detected QTLs associated with cold tolerance in rice bud burst stage will be conducive to further mining favorable genes and breeding of rice varieties under cold stress.

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