scholarly journals Evaluating the genetic effects of sex hormone traits on the development of mental traits: a polygenic score analysis and genome-wide genetic interaction analysis in UK Biobank cohort

2020 ◽  
Author(s):  
Xiao Liang ◽  
ShiQiang Cheng ◽  
Jing Ye ◽  
XiaoMeng Chu ◽  
Yan Wen ◽  
...  
Keyword(s):  
Alcohol Consumption ◽  
Fluid Intelligence ◽  
Genetic Interaction ◽  
Genetic Effects ◽  
Sex Hormone ◽  
Polygenic Risk Score ◽  
Uk Biobank ◽  
Middle Aged ◽  
Genome Wide ◽  
Middle Aged Adults

Abstract Objective: To evaluate the genetic effects of sex hormone traits on the development of mental traits in middle-aged adults.Methods: The SNPs associated with sex hormone traits were derived from a two-stage genome-wide association study (GWAS). Four sex hormone traits were selected in the current study, including sex hormone-binding globulin (SHBG), testosterone, bioavailable testosterone and estradiol. The polygenic risk score (PRS) of sex hormone traits were calculated from individual-level genotype data of the United Kingdom (UK) Biobank cohort. We then used logistic and linear regression models to assess the associations between individual PRS of sex hormone traits and the frequency of alcohol consumption, anxiety, intelligence and so on. Finally, genome-wide genetic interaction study (GWGIS) was performed to detect novel candidate genes interacting with the sex hormone traits on the development of fluid intelligence and the frequency of smoking and alcohol consumption by PLINK2.0.Results: We observed positive association between SHBG and the frequency of alcohol consumption (b=0.0101, p=3.84×10–11) in middle-aged males and females. In addition, estradiol was positively associated with the frequency of alcohol consumption (b=0.0128, p=1,96×10–8) in middle-aged males. Moreover, SHBG was associated with the frequency of alcohol consumption (b=0.0067, p=2.60×10–3) in middle-aged females. Finally, GWGIS identified one significant loci, Tenascin R (TNR) (rs34633780, p=3.45×10–8) interacting with total testosterone for fluid intelligence.Conclusion: Our study results support the genetic effects of sex hormone traits on the development of intelligence and the frequency of alcohol consumption in middle-aged adults in UK.

scholarly journals Evaluating the genetic effects of sex hormone traits on the development of mental traits: a polygenic score analysis and genome-wide genetic interaction analysis in UK Biobank cohort

2020 ◽  
Author(s):  
Xiao Liang ◽  
ShiQiang Cheng ◽  
Jing Ye ◽  
XiaoMeng Chu ◽  
Yan Wen ◽  
...  
Keyword(s):  
Alcohol Consumption ◽  
Fluid Intelligence ◽  
Genetic Interaction ◽  
Genetic Effects ◽  
Sex Hormone ◽  
Polygenic Risk Score ◽  
Uk Biobank ◽  
Middle Aged ◽  
Genome Wide ◽  
Middle Aged Adults

Abstract Objective: To evaluate the genetic effects of sex hormone traits on the development of mental traits in middle-aged adults.Methods: The SNPs associated with sex hormone traits were derived from a two-stage genome-wide association study (GWAS). Four sex hormone traits were selected in the current study, including sex hormone-binding globulin (SHBG), testosterone, bioavailable testosterone and estradiol. The polygenic risk score (PRS) of sex hormone traits were calculated from individual-level genotype data of the United Kingdom (UK) Biobank cohort. We then used logistic and linear regression models to assess the associations between individual PRS of sex hormone traits and the frequency of alcohol consumption, anxiety, intelligence and so on. Finally, genome-wide genetic interaction study (GWGIS) was performed to detect novel candidate genes interacting with the sex hormone traits on the development of fluid intelligence and the frequency of smoking and alcohol consumption by PLINK2.0.Results: We observed positive association between SHBG and the frequency of alcohol consumption (b=0.0101, p=3.84×10–11) in middle-aged males and females. In addition, estradiol was positively associated with the frequency of alcohol consumption (b=0.0128, p=1,96×10–8), fluid intelligence (b=0.0084, p=1.90×10–2) and the frequency of smoking (b=0.0054, p=1.77×10–2) in middle-aged males. Moreover, SHBG was associated with the frequency of alcohol consumption (b=0.0067, p=2.60×10–3), fluid intelligence (b=0.0067, p=4.25×10–2) and anxiety (b=-0.0071, p=3.79×10–2) in middle-aged females. Finally, GWGIS identified one significant loci, Tenascin R (TNR) (rs34633780, p=3.45×10–8) interacting with total testosterone for fluid intelligence.Conclusion: Our study results support the genetic effects of sex hormone traits on the development of intelligence and the frequency of alcohol consumption in middle-aged adults in UK.

scholarly journals Evaluating the genetic effects of sex hormone traits on the development of mental traits: a polygenic score analysis and gene-environment-wide interaction study in UK Biobank cohort

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Xiao Liang ◽  
ShiQiang Cheng ◽  
Jing Ye ◽  
XiaoMeng Chu ◽  
Yan Wen ◽  
...  
Keyword(s):  
Alcohol Consumption ◽  
Fluid Intelligence ◽  
Genetic Effects ◽  
Sex Hormone ◽  
Uk Biobank ◽  
Interaction Study ◽  
Middle Aged ◽  
Bioavailable Testosterone ◽  
Gene Environment ◽  
Middle Aged Adults

Abstract Objective To evaluate the genetic effects of sex hormone traits on the development of mental traits in middle-aged adults. Methods The SNPs associated with sex hormone traits were derived from a two-stage genome-wide association study (GWAS). Four sex hormone traits were selected in the current study, including sex hormone-binding globulin (SHBG), testosterone, bioavailable testosterone and estradiol. The polygenic risk score (PRS) of sex hormone traits were calculated from individual-level genotype data of the United Kingdom (UK) Biobank cohort. We then used logistic and linear regression models to assess the associations between individual PRS of sex hormone traits and the frequency of alcohol consumption, anxiety, intelligence and so on. Finally, gene-environment-wide interaction study (GEWIS) was performed to detect novel candidate genes interacting with the sex hormone traits on the development of fluid intelligence and the frequency of smoking and alcohol consumption by PLINK2.0. Results We observed positive association between SHBG and the frequency of alcohol consumption (b = 0.0101, p = 3.84 × 10–11) in middle-aged males and females. In addition, estradiol was positively associated with the frequency of alcohol consumption (b = 0.0128, p = 1.96 × 10–8) in middle-aged males. Moreover, bioavailable testosterone was associated with the fluid intelligence (b = − 0.0136, p = 5.74 × 10–5) in middle-aged females. Finally, GEWIS identified one significant loci, Tenascin R (TNR) (rs34633780, p = 3.45 × 10–8) interacting with total testosterone for fluid intelligence. Conclusion Our study results support the genetic effects of sex hormone traits on the development of intelligence and the frequency of alcohol consumption in middle-aged adults in UK.

scholarly journals Evaluating the genetic effects of sex hormone on the development of mental traits: a polygenic score analysis and genome-wide genetic interaction analysis in the UK Biobank cohort

2020 ◽  
Author(s):  
Xiao Liang ◽  
ShiQiang Cheng ◽  
Jing Ye ◽  
XiaoMeng Chu ◽  
Yan Wen ◽  
...  
Keyword(s):  
Alcohol Consumption ◽  
Fluid Intelligence ◽  
Genetic Interaction ◽  
Interaction Analysis ◽  
Genetic Effects ◽  
Sex Hormone ◽  
Uk Biobank ◽  
Genome Wide ◽  
Study Results ◽  
The Uk

Abstract Objective: To evaluate the genetic effects of sex hormone on the development of mental traits.Methods: The SNPs significantly associated with sex hormone traits were driven from a two-stage genome-wide association study (GWAS). Four sex hormone were selected in this study, including sex hormone-binding globulin (SHBG), testosterone, bioavailable testosterone and estradiol. The polygenic risk scores (PRS) of sex hormone traits were calculated from individual-level genotype data of the UK Biobank cohort. We then used logistic and linear regression models to assess the associations between individual PRS of sex hormone traits and the frequency of alcohol consumption, anxiety, intelligence and so on. Finally, genome-wide genetic interaction study (GWGIS) was performed to detect novel candidate genes interacting with the sex hormone on the development of fluid intelligence and the frequency of smoking and alcohol consumption by PLINK2.0.Results: We observed positive associations between SHBG and the frequency of alcohol consumption (b=0.01, p=3.84×10–11) in males and females. In addition, estradiol was positively associated with the frequency of alcohol consumption (b=0.01, p=1,96×10–8), fluid intelligence (b=0.01, p=1.90×10–2) and the frequency of smoking (b=0.01, p=1.77×10–2) in males. Moreover, SHBG was associated with the frequency of alcohol consumption (b=0.01, p=2.60×10–3), fluid intelligence (b=0.01, p=4.25×10–2) and anxiety (b=-0.01, p=3.79×10–2) in females. Finally, GWGIS identified one significant loci, Tenascin R (TNR) (rs34633780, p=3.45×10–8) interacting with total testosterone for fluid intelligence.Conclusion: Our study results support the genetic effects of sex hormone on the development of intelligence and the frequency of alcohol consumption.

scholarly journals Evaluating the genetic effects of sex hormone traits on the development of mental traits: a polygenic score analysis and gene-environment-wide interaction study in UK Biobank cohort

2020 ◽  
Author(s):  
Xiao Liang ◽  
ShiQiang Cheng ◽  
Jing Ye ◽  
XiaoMeng Chu ◽  
Yan Wen ◽  
...  
Keyword(s):  
Alcohol Consumption ◽  
Fluid Intelligence ◽  
Genetic Effects ◽  
Sex Hormone ◽  
Uk Biobank ◽  
Interaction Study ◽  
Middle Aged ◽  
Bioavailable Testosterone ◽  
Gene Environment ◽  
Middle Aged Adults

Abstract Objective: To evaluate the genetic effects of sex hormone traits on the development of mental traits in middle-aged adults.Methods: The SNPs associated with sex hormone traits were derived from a two-stage genome-wide association study (GWAS). Four sex hormone traits were selected in the current study, including sex hormone-binding globulin (SHBG), testosterone, bioavailable testosterone and estradiol. The polygenic risk score (PRS) of sex hormone traits were calculated from individual-level genotype data of the United Kingdom (UK) Biobank cohort. We then used logistic and linear regression models to assess the associations between individual PRS of sex hormone traits and the frequency of alcohol consumption, anxiety, intelligence and so on. Finally, gene-environment-wide interaction study (GEWIS) was performed to detect novel candidate genes interacting with the sex hormone traits on the development of fluid intelligence and the frequency of smoking and alcohol consumption by PLINK2.0.Results: We observed positive association between SHBG and the frequency of alcohol consumption (b=0.0101, p=3.84×10–11) in middle-aged males and females. In addition, estradiol was positively associated with the frequency of alcohol consumption (b=0.0128, p=1,96×10–8) in middle-aged males. Moreover, bioavailable testosterone was associated with the fluid intelligence (b=-0.0136, p=5.74×10-5) in middle-aged females. Finally, GEWIS identified one significant loci, Tenascin R (TNR) (rs34633780, p=3.45×10–8) interacting with total testosterone for fluid intelligence.Conclusion: Our study results support the genetic effects of sex hormone traits on the development of intelligence and the frequency of alcohol consumption in middle-aged adults in UK.

Polygenic Risk Scores for Kidney Function and Their Associations with Circulating Proteome, and Incident Kidney Diseases

2021 ◽  
pp. ASN.2020111599
Author(s):  
Zhi Yu ◽  
Jin Jin ◽  
Adrienne Tin ◽  
Anna Köttgen ◽  
Bing Yu ◽  
...  
Keyword(s):  
Kidney Function ◽  
Kidney Diseases ◽  
Association Studies ◽  
Polygenic Risk Score ◽  
Genome Wide Association Studies ◽  
Plasma Proteome ◽  
Uk Biobank ◽  
Polygenic Risk ◽  
Genome Wide ◽  
A Genome

Background: Genome-wide association studies (GWAS) have revealed numerous loci for kidney function (estimated glomerular filtration rate, eGFR). The relationship of polygenic predictors of eGFR, risk of incident adverse kidney outcomes, and the plasma proteome is not known. Methods: We developed a genome-wide polygenic risk score (PRS) for eGFR by applying the LDpred algorithm to summary statistics generated from a multiethnic meta-analysis of CKDGen Consortium GWAS (N=765,348) and UK Biobank GWAS (90% of the cohort; N=451,508), followed by best parameter selection using the remaining 10% of UK Biobank (N=45,158). We then tested the association of the PRS in the Atherosclerosis Risk in Communities (ARIC) study (N=8,866) with incident chronic kidney disease, kidney failure, and acute kidney injury. We also examined associations between the PRS and 4,877 plasma proteins measured at at middle age and older adulthood and evaluated mediation of PRS associations by eGFR. Results: The developed PRS showed significant associations with all outcomes with hazard ratios (95% CI) per 1 SD lower PRS ranged from 1.06 (1.01, 1.11) to 1.33 (1.28, 1.37). The PRS was significantly associated with 132 proteins at both time points. The strongest associations were with cystatin-C, collagen alpha-1(XV) chain, and desmocollin-2. Most proteins were higher at lower kidney function, except for 5 proteins including testican-2. Most correlations of the genetic PRS with proteins were mediated by eGFR. Conclusions: A PRS for eGFR is now sufficiently strong to capture risk for a spectrum of incident kidney diseases and broadly influences the plasma proteome, primarily mediated by eGFR.

scholarly journals Genome-wide association study of alcohol consumption and genetic overlap with other health-related traits in UK Biobank (N=112,117)

2017 ◽  
Author(s):  
Toni-Kim Clarke ◽  
Mark J. Adams ◽  
Gail Davies ◽  
David M. Howard ◽  
Lynsey S. Hall ◽  
...  
Keyword(s):  
Alcohol Consumption ◽  
Association Study ◽  
Genome Wide Association Study ◽  
Hdl Cholesterol ◽  
Genome Wide Association ◽  
P Value ◽  
Uk Biobank ◽  
Genome Wide ◽  
A Genome ◽  
Genetic Overlap

AbstractAlcohol consumption has been linked to over 200 diseases and is responsible for over 5% of the global disease burden. Well known genetic variants in alcohol metabolizing genes, e.g. ALDH2, ADH1B, are strongly associated with alcohol consumption but have limited impact in European populations where they are found at low frequency. We performed a genome-wide association study (GWAS) of self-reported alcohol consumption in 112,117 individuals in the UK Biobank (UKB) sample of white British individuals. We report significant genome-wide associations at 8 independent loci. These include SNPs in alcohol metabolizing genes (ADH1B/ADH1C/ADH5) and 2 loci in KLB, a gene recently associated with alcohol consumption. We also identify SNPs at novel loci including GCKR, PXDN, CADM2 and TNFRSF11A. Gene-based analyses found significant associations with genes implicated in the neurobiology of substance use (CRHR1, DRD2), and genes previously associated with alcohol consumption (AUTS2). GCTA-GREML analyses found a significant SNP-based heritability of self-reported alcohol consumption of 13% (S.E.=0.01). Sex-specific analyses found largely overlapping GWAS loci and the genetic correlation between male and female alcohol consumption was 0.73 (S.E.=0.09, p-value = 1.37 x 10−16). Using LD score regression, genetic overlap was found between alcohol consumption and schizophrenia (rG=0.13, S.E=0.04), HDL cholesterol (rG=0.21, S.E=0.05), smoking (rG=0.49, S.E=0.06) and various anthropometric traits (e.g. Overweight, rG=-0.19, S.E.=0.05). This study replicates the association between alcohol consumption and alcohol metabolizing genes and KLB, and identifies 4 novel gene associations that should be the focus of future studies investigating the neurobiology of alcohol consumption.

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