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PubMed1994

[Genetic analysis of a polygenic system of a quantitative character after negative and positive selection. I. General characteristics of the polygenic system].

Genetic analysis of phenotypic expression of the quantitative character controlled by an oligogenic mutation radius incompletus (ri) and a polygenic system in Drosophila melanogaster was carried out. Flies from the control line riC and two contrasting selection lines, riSR (positive selection) and riSN (negative selection) were crossed to the wild-type line riN. Proximal and distal segments of the longitudinal wing vein were measured in F2 ri/ri homozygotes. RiC and riN lines were shown to carry sets of polygenes with equivalent phenotypic contribution while selection lines (riSP and riSN) had an excess of polygenes of positive and negative effect, respectively. Striking similarity in some features of the polygenic system and localization of mobile genetic elements in the chromosomes of the lines was demonstrated.

Animals↗

PubMed2025

Robust pleiotropy-decomposed polygenic scores identify distinct contributions to elevated coronary artery disease polygenic risk.

BACKGROUND: Polygenic risk score (PRS) have proved to offer robust risk prediction for coronary artery disease (CAD). However, the global CAD PRS summarizes the joint effects of all the markers in the genome, masking potential genetic heterogeneity that may be important for disease interpretation and targeted interventions. METHODS: Using summary-level data, we identified 43 significant CAD-related traits based on genetic correlations, and further classified them into eight pleiotropy clusters based on their biological functions. We then partitioned the genome into 2,353 near-independent regions. Variants in each region were assigned to the trait most genetically similar to CAD, and then were labeled with the corresponding pleiotropy cluster. We grouped variants without labels into a ninth, non-specific cluster. The Pleiotropy Decomposed (PD) PRSs for each of the nine clusters were calculated using variants assigned to each cluster for 407,903 samples of European ancestry from the UK Biobank (UKBB). RESULTS: We decomposed the CAD PRS into nine PD-PRSs and further stratified individuals with high CAD-PRS into nine subgroups. Each PD-PRS accounted for a higher proportion of the global CAD-PRS within its corresponding subgroup than in the remaining subjects with high CAD-PRS (e.g., 25.2% (0.07) vs. 10.06% (0.07) for lipids-PD-PRS). Additionally, these subgroups showed distinct clinical features. For example, in the lipids-related subgroup, lipoprotein(a) and LDL-cholesterol levels were 67.5% and 18.3% higher, respectively, compared to the remaining high-risk individuals. Furthermore, significant interactions were observed between blood pressure and BP PD-PRS, and between current smoking and respiratory system PD-PRS. CONCLUSION: Our findings suggest that PD-PRSs may reveal substantial genetic and phenotypic heterogeneity among individuals with high CAD-PRS. The unique PD-PRS compositions of each individual can highlight the relative importance of different pleiotropic regions.

Humans↗

PubMed2026

Beyond Exons: Linking Noncoding Heritability and Polygenicity across Complex Human Traits and Disorders.

The genetic architecture of complex traits spans a continuum of polygenicity, yet it remains unclear how differences in polygenicity relate to the functional localization of SNP heritability across the genome. We use a MiXeR-based framework to partition heritability across exonic, intronic, and intergenic regions for 34 traits and introduce a likelihood-based annotation contribution score that quantifies annotation-specific impact on heritability. Exons explain a minority of heritability, and their contribution decreases with increasing polygenicity, from an average of 22% in less polygenic somatic diseases and biomarkers to 13% in highly polygenic psychiatric and cognitive phenotypes. Intergenic fractions show the opposite trend, whereas intronic fractions remain relatively stable. Analysis of a broader set of functional annotations reveals systematic differences along the polygenicity axis: highly polygenic traits show stronger contributions from comparative genomics and variant-effect scores, whereas less polygenic traits show stronger contributions in promoter, transcription, and chromatin annotations. Together, these results indicate that the functional partitioning of heritability systematically varies with polygenicity, pointing to a shift from gene-proximal regulatory architectures to architectures shaped by numerous dispersed regulatory effects as a key determinant of differences in polygenicity across traits.

Journal Article↗

PubMed2026

Beyond exons: Linking noncoding heritability and polygenicity across complex human traits and disorders.

The genetic architecture of complex traits spans a continuum of polygenicity, yet it remains unclear how differences in polygenicity relate to the functional localization of SNP heritability across the genome. We use a MiXeR-based framework to partition heritability across 74 functional annotations covering exonic, intronic, and intergenic regions for 34 complex traits and introduce a likelihood-based annotation contribution score that quantifies annotation-specific impact on heritability. Exons account for a minority of heritability, and their contribution decreases with increasing polygenicity, from an average of 22% in less-polygenic somatic diseases and biomarkers to 13% in highly polygenic psychiatric and cognitive phenotypes. Intergenic fractions show the opposite trend, whereas intronic fractions remain relatively stable. Analysis of the broader set of functional annotations also reveals systematic differences along the polygenicity axis: highly polygenic traits show stronger contributions from comparative genomics and variant-effect scores, whereas less-polygenic traits show stronger contributions from promoter, transcription, and chromatin annotations. Together, these results indicate that the functional partitioning of heritability systematically varies with polygenicity, shifting from gene-proximal regulatory architectures to architectures shaped by numerous dispersed regulatory effects.

MiXeR↗

PubMed2025

Polygenic Susceptibility in Peripartum, Alcohol-Induced, and Cancer Therapy-Related Cardiomyopathies.

IMPORTANCE: Rare monogenic variants linked to nonischemic dilated cardiomyopathy (DCM) are enriched among individuals with secondary cardiomyopathies, such as peripartum (PPCM), alcohol-induced (ACM), and cancer therapy-related (CCM) cardiomyopathies. However, it remains unclear whether a polygenic predisposition to DCM also contributes to these conditions. OBJECTIVE: To assess the association of a DCM polygenic score with PPCM, ACM, and CCM, and to evaluate the contributions of monogenic and polygenic susceptibilities to these secondary cardiomyopathies. DESIGN, SETTING, AND PARTICIPANTS: This was a retrospective genetic association analysis of data from the Mass General Brigham (MGB) Biobank (n = 42 137, 2008-2025), with replication in the UK Biobank (n = 295 160, 2005-2010), FinnGen (n = 417 950, 2017-2025), and the Veterans Affairs Million Veteran Program (n = 516 066, 2011-2025). In MGB Biobank, medical records were reviewed to ascertain secondary cardiomyopathy cases and antecedent clinical risk factors. EXPOSURES: DCM polygenic risk score and DCM monogenic variants. MAIN OUTCOMES AND MEASURES: The primary outcomes were the association of the DCM polygenic risk score with PPCM, ACM, and CCM and the prevalence of monogenic variants and a high polygenic score among individuals with cardiomyopathy. RESULTS: The mean (SD) age in the MGB Biobank was 55.7 (17.0) years at enrollment, and 24 551 (58.3%) were female. Across the 4 study cohorts, 3414 individuals with secondary cardiomyopathy were identified, including 70 with PPCM, 2281 with ACM, and 1063 with CCM. The DCM polygenic score was associated with PPCM (odds ratio [OR], 1.82 per SD; 95% CI, 1.43-2.30), ACM (OR, 1.56; 95% CI,1.34-1.82), and CCM (OR, 1.64; 95% CI,1.24-2.15) (all with P < .001). Monogenic variants were enriched but present in 7 of 113 individuals with medical record-reviewed cardiomyopathy in MGB, while 66 had a high polygenic score, which conferred an approximately 3-fold increased odds of cardiomyopathy. Most individuals with cardiomyopathy lacked antecedent clinical risk factors. CONCLUSIONS AND RELEVANCE: In this cohort study, individuals with PPCM, ACM, and CCM were enriched for monogenic DCM variants and a high DCM polygenic score, suggesting a shared genetic susceptibility influenced by distinct environmental precipitants. These findings support a shared genetic architecture between secondary cardiomyopathies and DCM, although additional work with larger numbers of individuals with cardiomyopathy is needed to confirm these findings.

Humans↗

PubMed2001

[Computer modeling of joint selection response of MGE patterns and a polygenic system].

Using computer simulation, selection response of three genome patterns--polygenes, mobile genetic elements (MGEs), and labels of identity by origin (LIOs)--were studied. In each generation of selection, variability of each pattern type was described by on UPGMA tree. Stringent positive truncation selection on an additive polygenic trait and recombination between segments of the genetic map were considered. MGEs were classified into three groups: modifiers (enhancers) of the polygenic expression, markers, and independent copies. It was shown that at generations 30 to 40, 95-96% and 70-80% of respectively enforced and non-enforced active polygenic alleles were fixed (2-3% and 16-17% lost). In all generations, Hkn < or = Dkn of the length of the maximal route along the tree. At the same time, modifier MGEs were fixed for 85-88% (lost for 11-12%); marker MGEs, for 60-70 (lost for 21-25%); and independent copies, for 30-40 (lost for 50-60%). The behavior of independent MGE copies was generally consistent with the predictions of the genetic drift theory, modifier MGEs behaved similarly to the modified polygenes, and marker MGEs exhibited intermediate properties. The LIO patterns showed rapid homozygotization: their variability dropped dramatically between generations 10 and 30. In F50, the final consensus pattern of polygenes included 16 out of 18 enforced and 18 out of 21 non-enforced polygenic alleles. The fixation/loss ratios were 16:3 for modifier MGEs, 15:6 for marker MGEs, and 25:28 (with 7 polymorphic) for independent copies. The LIO consensus pattern contained 13 out of 100 original markers, which formed 26 fragments of one to ten map segments in size; 21 fragments contained active polygenic alleles, and 14 of them had also modifier MGEs. Recombinational shuffling of patterns was not completed. In the course of selection, active polygenic alleles take along adjacent segments, including those containing modifier MGEs and markers. These constitute the conservative part of all consensus patterns while the remaining segments are random.

Computer Simulation↗

PubMed1997

An approximate model of polygenic inheritance.

The finite polygenic model approximates polygenic inheritance by postulating that a quantitative trait is determined by n independent, additive loci. The 3n possible genotypes for each person in this model limit its applicability. CANNINGS, THOMPSON, and SKOLNICK suggested a simplified, nongenetic version of the model involving only 2n + 1 genotypes per person. This article shows that this hypergeometric polygenic model also approximates polygenic inheritance well. In particular, for noninbred pedigrees, trait means, variances, covariances, and marginal distributions match those of the ordinary finite polygenic model. Furthermore as n --> infinity, the trait values within a pedigree collectively tend toward multivariate normality. The implications of these results for likelihood evaluation under the polygenic threshold and mixed models of inheritance are discussed. Finally, a simple numerical example illustrates the application of the hypergeometric polygenic model to risk prediction under the polygenic threshold model.

Female↗

PubMed1999

[Population dynamics of the additive polygenic system under truncation selection].

Common features of the equations describing dynamics of the additive polygenic system under truncation selection are summarized. A combination of parameters playing the role of the effective selective pressure on the ith polygenic locus was revealed. The product of mean relative fitnesses of the individual polygenic loci, [formula: see text], was shown to play the role of relative mean fitness of the polygenic population. This value depends on the measurable parameters of the character distribution in the population: [formula: see text]. It was shown that under the constant population number during truncation selection, the characteristic of the best genotype increases, [formula: see text]; which is also a product of the frequencies of preferable genotypes at individual polygenic loci. This value plays the role of the proportion of the number of the best ("champion") genotype in the population. In fact, this is the champion genotype polygene consensus pattern frequency, which a priori indicates the possibility of the champion pattern fixation. The analogue of Haldane's dilemma for the polygenic system which restrict the number of polygenes simultaneously subjected to adaptive evolution [formula: see text] was obtained for the case of constant effective population number (Ne = const).

Genotype↗

PubMed2026

Genome-wide association, polygenic risk scores, and machine learning for chronic post-surgical pain risk stratification: A UK biobank study.

Chronic post-surgical pain is a prevalent and debilitating complication following surgery, representing a clinical challenge. Despite the established heritability of pain phenotypes, large-scale genetic studies remain limited. This study aimed to identify genetic variants associated with chronic post-surgical pain, develop polygenic risk scores, and integrate these with clinical features for risk prediction. UK Biobank data from 47,836 participants (2490 cases and 45,346 controls) were split into training (80%; n = 38,268) and validation (20%; n = 9568) sets prior to analysis. A genome-wide association study was conducted on the training set only, across 19 million variants, and polygenic risk scores were constructed and integrated with clinical features in a logistic regression framework. Two close, rare, imputed signals crossed the genome-wide significance threshold but lacked local linkage-disequilibrium support, while 220 variants crossed the suggestive threshold. In the held-out validation set, cases had higher mean polygenic risk scores than controls (0.138 vs. -0.021; Cohen's d = 0.16, p < 0.001). A logistic regression model integrating clinical features and polygenic risk scores achieved an area under the curve of 0.639 (95% CI: 0.583-0.693), higher than models using either feature set alone. The polygenic risk score for chronic post-surgical pain was among the most important predictors. Risk stratification revealed the top quartile had 3.84-fold higher odds of chronic post-surgical pain than the bottom quartile (95% CI: 2.00-7.37). These findings suggest a possible modest genetic contribution to chronic post-surgical pain. Polygenic risk scores may complement clinical factors in surgical risk stratification. PERSPECTIVE: Chronic post-surgical pain may have a modest genetic contribution. This UK Biobank study identified over 220 variants at suggestive significance and constructed a polygenic risk score that was significantly elevated in cases. A combined clinical-genomic model achieved a 3.84-fold difference in odds across predicted-risk quartiles.

Chronic post-surgical pain↗

PubMed2001

Effect of polygenes on Xiong's transmission disequilibrium test of a QTL in nuclear families with multiple children.

The transmission disequilibrium test (TDT), originally developed for mapping disease genes, has recently been extended to identify quantitative trait loci (QTL). For quantitative traits important for human health, generally multiple QTLs are involved. In the investigation of the statistical properties of the TDT, background polygenes (QTLs other than the QTL under test) generally have not been explicitly considered. The effects of background polygenes on the statistical properties of the TDT are thus largely unknown. Investigation of these effects will provide more realistic analyses of the statistical properties of the TDT under biologically plausible situations, and thus provide more accurate guidelines on the application of the TDT in practice. A general TDT (TDT(G)) has been developed to test linkage of a QTL in nuclear families that may be composed of more than one heterozygous parent and multiple children. Using the TDT(G) as an example, we develop an analytical method to investigate the effects of background polygenes on the power of the TDT. The accuracy of our analytical method is validated by computation simulations. We found that the power of the TDT(G) is increased with background polygenes when more than one child is employed in nuclear families, and the effect is stronger with more children per family recruited for study. The power of the TDT(G) increases dramatically when the number of children recruited from each nuclear family increases from one to two or from two to three. The type one error rate is not affected by the presence of background polygenes. The results of this study should be of theoretical significance in generalizing the investigation of the TDT to biologically plausible situations with background polygenes. They should also be of practical values in providing guidance on the recruitment of nuclear families with multiple children with the TDT(G).

Computer Simulation↗

PubMed2000

Differing relationships of methylene tetrahydrofolate reductase genotypes with cardiovascular risk in familial and polygenic hypercholesterolaemia.

BACKGROUND: Plasma homocysteine and the methylene tetrahydrofolate reductase C677T polymorphism have been suggested as being risk factors for cardiovascular disease. OBJECTIVE: To determine whether plasma homocysteine and the methylene tetrahydrofolate reductase C677T polymorphism are risk factors for coronary heart disease in patients with heterozygous familial hypercholesterolaemia as compared with those with polygenic hyperlipidaemia. METHODS: Plasma homocysteine and the methylene tetrahydrofolate reductase polymorphism were assessed with other risk factors in 112 patients with familial hypercholesterolaemia and 72 patients with polygenic hyperlipidaemia, of whom 29 (25.8%) and 30 (41%) respectively had established cardiovascular disease and in 100 healthy normal subjects. RESULTS: Plasma homocysteine was not significantly elevated in patients with and without coronary heart disease with familial hypercholesterolaemia or polygenic hyperlipidaemia compared with controls. The allele frequencies for C677T were significantly different in patients with coronary heart disease and with polygenic hyperlipidaemia (0.35 versus 0.29) (P = 0.02) as opposed to those with coronary heart disease and familial hypercholesterolaemia (0.25 versus 0.30) (P = 0.63). Methylene tetrahydrofolate reductase genotype but not homocysteine had a weak association with coronary heart disease in logistic regression analysis in patients with polygenic hyperlipidaemia (P = 0.05) but neither methylene tetrahydrofolate reductase genotype or plasma homocysteine was a risk factor in patients with familial hypercholesterolaemia. CONCLUSION: Whilst methylene tetrahydrofolate reductase genotype may be a weak risk factor for coronary heart disease in polygenic hyperlipidaemia as opposed to familial hypercholesterolaemia, homocysteine does not seem to be an important risk factor for coronary heart disease in patients in southern UK.

Adult↗

PubMed2026

Kv11.1 (hERG) Protein Interaction Networks Connect Endocytic Trafficking to Polygenic Influences on Cardiac Repolarization.

Polygenic scores (PGS) capture the combined effect of many common genetic variants on quantitative traits and disease risk, yet their functional consequences at the protein level remain poorly defined. Here, we integrated quantitative and interaction proteomics to resolve how polygenic liability for cardiac repolarization manifests in human cells. We studied human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) from donors with extreme PGS for QT interval duration, a clinically relevant electrophysiologic trait associated with arrhythmia risk. Global quantitative proteomics revealed increased abundance of mitochondrial proteins in high-PGS cardiomyocytes. To define protein network-level effects on a key repolarizing ion channel, we performed multiplexed affinity purification-mass spectrometry (AP-MS) of Kv11.1. While mitochondrial changes did not directly explain Kv11.1-associated complexes, interactome analysis revealed increased association of Kv11.1 with myosin motor proteins and endosomal recycling machinery in high-PGS cells. These findings suggest altered channel trafficking dynamics of Kv11.1, distinct from the trafficking defects observed in monogenic Kv11.1 variants. Together, these data show that integrating global and interaction proteomics can resolve how polygenic variation reshapes protein networks. Future work using these methods could connect genomic risk to subcellular remodeling and our work provides a generalizable framework to probe the proteomic basis of complex traits. SIGNIFICANCE STATEMENT: Polygenic scores (PGS) predict disease risk, but how biological pathways are influenced by these common variants remains difficult to define. We generated human induced pluripotent stem cells from individuals with extreme high- and low- PGS for QT interval, a key electrocardiographic measure linked to arrhythmia risk. By combining global proteomics and interactomics for a common ion channel involved in regulating the QT interval (Kv11.1) we found potential mechanisms that are influenced by common genetic traits in patients. Our work provides an approach to connect polygenic scores to pathway-level molecular mechanisms in human cells and a general framework for uncovering how complex genetic architecture drives disease-relevant biology.

AP-MS↗

PubMed2026

Polygenic and monogenic adaptation drive evolutionary rescue at different magnitudes of environmental change.

Understanding the genetic basis of rapid adaptation is key to predicting species' evolutionary responses to environmental change. However, it is still debatable whether many small-effect mutations or a few large-effect mutations underlie rapid adaptation, and how this knowledge can predict population survival or extinction. To address this question, we performed a series of ecologically grounded forward-in-time genetic simulations to study rapid adaptation and extinction with increasing magnitudes of environmental change. These simulations were seeded with genomic variation of the plant Arabidopsis thaliana to have a realistic genomic structure, with one (monogenic) to 1,000 (polygenic) variants with varying heritabilities contributing to an environmental adaptive trait. Our results revealed two distinct scenarios of rapid adaptation and population rescue. Under small-to-moderate environmental shifts, high polygenic traits increased evolutionary rescue probability. Under extreme environmental shifts, high polygenic traits lead predictably to extinction, yet monogenic traits sometimes produce one-off winning adaptive genotypes. We interpret our rapid evolutionary rescue findings in terms of the fundamental theorem of natural selection, where trait polygenicity shapes the distribution of genetic variance in fitness across replicates and, in turn, the probability of population survival, with polygenic architectures producing more stable and predictable fitness variance and monogenic architectures generating highly skewed and variable outcomes. These results highlight the insights genomics gives us into the (un)predictability of species' evolutionary responses to global change, with management implications for assisted adaptation and conservation.

Arabidopsis↗

PubMed2006

Genetic analysis of oil content in Brassica napus L. using mixed model of major gene and polygene.

The joint segregation analysis of a mixed genetic model of major gene plus poly-gene was conducted to study the inheritance of oil content in Brassica napus L.. Five populations, i.e the populations of 2 parents (P1 and P2), F1, F2 and F2:3 (derived from F2) family, from each of the two crosses (1141B x Ken C-1, 32B x Ken C1-2) were investigated.The frequency distributions of oil content in F2 and F2:3 family populations show characteristics of a mixed normal distribution, which indicated that the inheritance of oil content followed a major gene plus poly-gene model. Twenty-one genetic models were established, which could be classified into five types: one and two major genes, polygenes, one and two major genes plus polygenes. The most suitable genetic model could be selected using Akaike's Information Criterion and the fitness of the selected one could be examined by a set of tests. Results show that genetic model D-2 is the most fitting genetic model for the trait. In other words, oil content in oilseed rape is controlled by one additive major gene plus additive and dominance polygenes. For cross 1 (1141B x Ken C1-1) the heritabilities of major gene and poly-genes in F2 are 68.21% and 27.17%, respectively, and in F2:3 are 81.70% and 16.80%, respectively. The additive effect of major gene is -1.74, which indicates that the locus of the allele in parent 1141B may decrease the oil content, but that in parent Ken C1-1 may increase it. The additive and dominance effects of the polygenes are 1.20 and -1.93, respectively. For cross 2 (32B x Ken C1-2) the heritabilities of major gene and polygenes in F2 are 66.20% and 28.10%, respectively, and in F2:3 were 81.00% and 14.90%, respectively. The additive effect of major gene was -3.74, which also indicates that the locus of the allele in parent 32B may decrease the oil content, but that in parent Ken C1-2 may increase it. The additive and dominance effects are -1.99 and 0.93, respectively. The heritability of the major gene in F2:3 is higher than that in F2 in both crosses, so it would be more efficent to conduct selection in F2:3 families for high oil content in breeding.

Brassica napus↗

PubMed1977

Spontaneous and ethyl methanesulfonate-induced mutations controlling viability in Drosophila melanogaster. II. Homozygous effect of polygenic mutations.

Polygenic mutations affecting viability were accumulated on the second chromosome of Drosophila melanogaster by treating flies with EMS in successive generations. The treated chromosomes were later made homozygous and tested for their effects on viability by comparison of the frequency of such homozygotes with that of other genotypes in the same culture. The treated wild-type chromosomes were kept heterozygous in Pm/+ males by mating individual males in successive generations to Cy/Pm females. The number of generations of accumulation was 1 to 30 generations, depending on the concentration of EMS. A similar experiment for spontaneous polygenic mutations was also conducted by accumulating mutations for 40 generations. The lower limit of the spontaneous mutation rate of viability polygenes is estimated to be 0.06 per second chromosome per generation, which is about 12 times as high as the spontaneous recessive lethal mutation rate, 0.005. EMS-induced polygenic mutations increase linearly with the number of treated generations and with the concentration of EMS. The minimum mutation rate of viability polygenes is about 0.017 per 10(-4)m, which is only slightly larger than the lethal rate of 0.013 per 10(-4) m. The maximum estimate of the viability reduction of a single mutant is about 6 to 10 percent of the normal viability. The data are consistent with a constant average effect per mutant at all concentrations, but this is about three times as high as that for spontaneous mutants. It is obvious that one can obtain only a lower limit for the mutation rate, since some mutants may have effects so near to zero that they cannot be detected. The possibility of measuring something other than the lower limit is discussed. The ratio of the load due to detrimental mutants to that caused by lethals, the D/L ratio, is about 0.2 to 0.3 for EMS-induced mutants, as compared to about 0.5 for spontaneous mutants. This is to be expected if EMS treatment produces a large fraction of small deletions and other chromosome rearrangements which are more likely to be lethal.

Animals↗

PubMed2026

Obesity Polygenic Risk and Healthy Lifestyle Interactions on Weight Trajectories in Women and Men.

BACKGROUND: Genetics and environmental factors contribute to obesity risk, but the extent to which healthy behaviors can offset genetic susceptibility remains unclear. We examined the interaction between obesity polygenic risk and a composite healthy lifestyle score on body mass index (BMI) trajectories in women and men. METHODS: We analyzed 13 780 women from the Nurses' Health Study and 8242 men from the Health Professionals Follow-Up Study, all of European ancestry and free of major chronic disease at baseline. The lifestyle score comprised American Heart Association Essential 8 components (nonsmoking, physical activity, healthy eating, adequate sleep) plus moderate alcohol intake, modeled as a time-varying variable. A genome-wide polygenic score for BMI was derived from genome-wide association study. Adjusted linear mixed-effects models estimated associations and interactions on biennial BMI measures over up to 26 years. RESULTS: Each SD increase in the polygenic score was associated with 1.80 kg/m2 (95% CI, 1.72-1.87) and 1.12 kg/m2 (95% CI, 1.06-1.19) higher BMI in women and men, respectively. Significant interactions between the polygenic score and healthy lifestyle score (both P<0.05) showed a dose-response attenuation of the genetic effects with healthier lifestyles. Comparing the healthiest with the least healthy lifestyle groups, genetic effects on BMI were 35% lower in women and 28% lower in men. In sensitivity analyses, higher diet quality and physical activity consistently attenuated genetic associations in both cohorts, whereas current smoking showed similar effects in women only. CONCLUSIONS: Adherence to a healthier lifestyle attenuated the association between obesity polygenic risk and BMI in a dose-response manner.

Humans↗

PubMed2000

[Major-polygene effect analysis of resistance to bacterial blight (Xanthomonas campestris pv. oryzae) in rice].

Five crosses between resistance and susceptible were analyzed to study major-polygene effect using major-polygene mixed mode. The result showed that 3 of 5 crosses were controlled by both major gene and polygene. In addition, there were large variation of additive effect, variance as well as heredity of major gene polygene in 3 crosses. Major gene was predominant in resistant variation, but durability should be considered. We suggested that construct major-polygene system be constructed in the long run in breeding program to ensure a durable and high level of resistance to constrain fluctuation of races of Xanthomonas campestris pv. oryzae population.

Oryza↗

PubMed1982

[Polygenic inheritance of familial malignant melanoma].

Familial occurrence of malignant melanoma is mostly due to a hereditary disposition which is phenotypically characterized by light complexion and multiple precursor nevi. The inheritance of this disposition is not monogenic but polygenic. The following arguments are in favor of polygenic inheritance: Lack of a uniform pattern of transmission, frequent sporadic occurrence of this phenotype, variable intensity of manifestation within the same family, evidence for polygenic inheritance of fair complexion, and demonstration of polygenic inheritance of melanoma in Xiphophorin fish. In melanoma families, children of affected women develop melanoma more frequently than children of affected men. The authors interpret this phenomenon as a manifestation of the Carter effect. This mechanism is proposed as a new argument in favor of a polygenic inheritance of familial malignant melanoma.

ABO Blood-Group System↗