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Genome-wide association study and Mendelian randomization analysis provide insights for improving rice yield potential.

ABSTRACT: Rice yield per plant has a complex genetic architecture, which is mainly determined by its three component traits: the number of grains per panicle (GPP), kilo-grain weight (KGW), and tillers per plant (TP). Exploring ideotype breeding based on selection for genetically less complex component traits is an alternative route for further improving rice production. To understand the genetic basis of the relationship between rice yield and component traits, we investigated the four traits of two rice hybrid populations (575 + 1495 F₁) in different environments and conducted meta-analyses of genome-wide association study (meta-GWAS). In total, 3589 significant loci for three components traits were detected, while only 3 loci for yield were detected. It indicated that rice yield is mainly controlled by minor-effect loci and hardly to be identified. Selecting quantitative trait locus/gene affected component traits to further enhance yield is recommended. Mendelian randomization design is adopted to investigate the genetic effects of loci on yield through component traits and estimate the genetic relationship between rice yield and its component traits by these loci. The loci for GPP or TP mainly had a positive genetic effect on yield, but the loci for KGW with different direction effects (positive effect or negative effect). Additionally, TP (Beta = 1.865) has a greater effect on yield than KGW (Beta = 1.016) and GPP (Beta = 0.086). Five significant loci for component traits that had an indirect effect on yield were identified. Pyramiding superior alleles of the five loci revealed improved yield. A combination of direct and indirect effects may better contribute to the yield potential of rice. Our findings provided a rationale for using component traits as indirect indices to enhanced rice yield, which will be helpful for further understanding the genetic basis of yield and provide valuable information for improving rice yield potential.

SUBMITTER: Su J

PROVIDER: S-EPMC7994632 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundAge at menarche has been associated with various health outcomes. We aimed to identify potential causal effects of age at menarche on health-related traits in a hypothesis-free manner.MethodsWe conducted a Mendelian randomization phenome-wide association study (MR-pheWAS) of age at menarche with 17,893 health-related traits in UK Biobank (n = 181,318) using PHESANT. The exposure of interest was the genetic risk score for age at menarche. We conducted a second MR-pheWAS after excluding SNPs associated with BMI from the genetic risk score, to examine whether results might be due to the genetic overlap between age at menarche and BMI. We followed up a subset of health-related traits to investigate MR assumptions and seek replication in independent study populations.ResultsOf the 17,893 tests performed in our MR-pheWAS, we identified 619 associations with the genetic risk score for age at menarche at a 5% false discovery rate threshold, of which 295 were below a Bonferroni-corrected P value threshold. These included potential effects of younger age at menarche on lower lung function, higher heel bone-mineral density, greater burden of psychosocial/mental health problems, younger age at first birth, higher risk of childhood sexual abuse, poorer cardiometabolic health, and lower physical activity. After exclusion of variants associated with BMI, the genetic risk score for age at menarche was related to 37 traits at a 5% false discovery rate, of which 29 were below a Bonferroni-corrected P value threshold. We attempted to replicate findings for bone-mineral density, lung function, neuroticism, and childhood sexual abuse using 5 independent cohorts/consortia. While estimates for lung function, higher bone-mineral density, neuroticism, and childhood sexual abuse in replication cohorts were consistent with UK Biobank estimates, confidence intervals were wide and often included the null.ConclusionsThe genetic risk score for age at menarche was related to a broad range of health-related traits. Follow-up analyses indicated imprecise evidence of an effect of younger age at menarche on greater bone-mineral density, lower lung function, higher neuroticism score, and greater risk of childhood sexual abuse in the smaller replication samples available; hence, these findings need further exploration when larger independent samples become available.

Project description:BackgroundObservational studies have identified various associations between neuroimaging alterations and neuropsychiatric disorders. However, whether such associations could truly reflect causal relations remains still unknown.ResultsHere, we leveraged genome-wide association studies (GWAS) summary statistics for (1) 11 psychiatric disorders (sample sizes varied from n = 9,725 to 1,331,010); (2) 110 diffusion tensor imaging (DTI) measurement (sample size n = 17,706); (3) 101 region-of-interest (ROI) volumes, and investigate the causal relationship between brain structures and neuropsychiatric disorders by two-sample Mendelian randomization. Among all DTI-Disorder combinations, we observed a significant causal association between the superior longitudinal fasciculus (SLF) and the risk of Anorexia nervosa (AN) (Odds Ratio [OR] = 0.62, 95 % confidence interval: 0.50 ~ 0.76, P = 6.4 × 10- 6). Similar significant associations were also observed between the body of the corpus callosum (fractional anisotropy) and Alzheimer's disease (OR = 1.07, 95 % CI: 1.03 ~ 1.11, P = 4.1 × 10- 5). By combining all observations, we found that the overall p-value for DTI - Disorder associations was significantly elevated compared to the null distribution (Kolmogorov-Smirnov P = 0.009, inflation factor λ = 1.37), especially for DTI - Bipolar disorder (BP) (λ = 2.64) and DTI - AN (λ = 1.82). In contrast, for ROI-Disorder combinations, we only found a significant association between the brain region of pars triangularis and Schizophrenia (OR = 0.48, 95 % CI: 0.34 ~ 0.69, P = 5.9 × 10- 5) and no overall p-value elevation for ROI-Disorder analysis compared to the null expectation.ConclusionsAs a whole, we show that SLF degeneration may be a risk factor for AN, while DTI variations could be causally related to some neuropsychiatric disorders, such as BP and AN. Also, the white matter structure might have a larger impact on neuropsychiatric disorders than subregion volumes.

Project description:IntroductionThe causal association between modifiable risk factors and erectile dysfunction (ED) remains unclear, which hinders the early identification and intervention of patients with ED. The present study aimed to clarify the causal association between 42 predominant risk factors and ED.MethodsUnivariate Mendelian Randomization (MR), multivariate MR, and mediation MR analyses were used to investigate the causal association between 42 modifiable risk factors and ED. Combined results were pooled from two independent ED genome-wide association studies to verify the findings.ResultsGenetically predicted body mass index (BMI), waist circumference, trunk fat mass, whole body fat mass, poor overall health rating, type 2 diabetes, basal metabolic rate, adiponectin, cigarette consumption, insomnia, snoring, hypertension, stroke, ischemic stroke, coronary heart disease, myocardial infarction, heart failure, and major depressive disorder were found to increase the risk of ED (all P < 0.05). Additionally, genetic liability to higher body fat percentage and alcohol consumption were suggestively associated with an increased risk of ED (P < 0.05 and adjusted P > 0.05). Genetic predisposition to higher sex hormone-binding globulin (SHBG) levels could decrease the risk of ED (P < 0.05). No significant association was detected between lipid levels and ED. Multivariate MR identified type 2 diabetes, basal metabolic rate, cigarette consumption, hypertension, and coronary heart disease as risk factors for ED. The combined results confirmed that waist circumference, whole body fat mass, poor overall health rating, type 2 diabetes, basal metabolic rate, adiponectin, cigarette consumption, snoring, hypertension, ischemic stroke, coronary heart disease, myocardial infarction, heart failure, and major depressive disorder could increase the risk of ED (all P < 0.05), while higher SHBG decreased the risk of ED (P = 0.004). There were suggestive significances of BMI, insomnia, and stroke on ED (P < 0.05 and adjusted P > 0.05).ConclusionThis comprehensive MR study supported the causal role of obesity, type 2 diabetes, basal metabolic rate, poor self-health rating, cigarette and alcohol consumption, insomnia and snoring, depression, hypertension, stroke, ischemic stroke, coronary heart disease, myocardial infarction, heart failure, SHBG, and adiponectin in the onset and development of ED.

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Genome-wide association study and Mendelian randomization analysis provide insights for improving rice yield potential.

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