Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “polygenicity”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 667 records · Page 37Linked to original sources
PubMed2001

[Development and expression process of inheritance of resistance to cotton worm (Prodenia litura) in soybeans].

Cotton worm [Prodenia litura(Fabricius)] was one of the major leaf-feeders for soybeans in Southern China. Resistance to leaf-feeders has been recognized as one of the major breeding target traits in the National Soybean Breeding Program. This paper deals with the study of inheritance of resistance of soybeans to cotton worm [Prodenia litura(Fabricius)]. P1, P2, F1, F2, F2:3 of four susceptible x resistant crosses, i.e. N21297 x N1178-2-2, N21266 x N23860, N119-1 x N1178-2-2 and N21266 x N3039, were used in the study. The materials were planted in net room under artificial infestation in 1996-1998. The data of defoliation percentage of successive development stages, during cotton worm damage period were obtained and collected for genetic analysis. The segregation analysis methods for major genes plus polygene mixed inheritance model developed by Gai et al. were used to identify the genetic system of resistance. The results from joint analyses of multiple segregating generations as well as from analyses of single F2 or F2:3 generations of the four crosses showed a two major genes plus polygene mixed inheritance model at fully developed stages of resistance while one or two major genes with or without polygene were observed at other stages. Between the two major genes, the additive effect of one locus was from 1.56 to 9.89(%, defoliation), another from -3.79 to 3.75(%, defoliation). The heritability values of major genes were estimated as 70.40%-99.21%, greater than those of polygene which were only 0.00%-22.29%. Therefore, in the improvement of resistance to cotton worm, major gene resistance should be considered at first.

Animals↗
PubMed2002

[Genetics study on photo- and thermo-sensitive genic male sterility of indica rice (O. satival L.)].

The sterility segregation and its genetic patterns of indica P(T)GMS rice were analyzed mainly based on the investigation of bagged seed-set of individuals in reciprocal F2 population from the crosses between P(T)GMS lines of different origin and typical indica conventional varieties of different ecotype under long day-length and high temperature condition by using the software of the maximum likelihood method. The results showed that the sterility of Annong S-1, Hengnong S-1, and W6154S, of which the sterility alteration was mainly induced by temperature fluctuation, was controlled by one major recessive gene. But the sterility of W7415S was controlled by more than two major recessive genes. Apart from the major recessive gene, there was a group of polygenes in controlling of the sterility segregation in F2 population. Moreover, the polygenic variance was different from line to line. It implied that the polygenes of W6154S or W7415S was far more complicated than that of Annong S-1 and Hengnong S-1 according to the maximum likelihood method. All the conventional indica varieties of different ecotypes possessed the major dominant fertility genes. Meanwhile, the genetic background in different ecotype conventional varieties, the essentiality of which lies in the existence of polygenes, was different and influenced the major gene expression deeply. It was also indicated that genetic background of middle-season variety Nanjing 11 was more complicated than that of early-season variety Erjiuqing and late-season variety GER-1 as well. Finally, the differences of drift in critical temperature inducing male sterility of P(T)GMS lines (for short term DCT) and the strategy of breeding practically usable P(T)GMS line with slighter DCT were discussed in the paper.

Crosses, Genetic↗
PubMed2005

[Segregation analysis of genetic system of quantitative traits in plants].

Based on the traditional polygene inheritance model of quantitative traits, the mixed major gene and polygene inheritance model was raised and considered as the general model, while pure major gene or pure polygene inheritance model being only the specific case of the general model. From the proposed theory, the segregation analysis procedure was established for studying the genetic system of quantitative traits of plants. At present this procedure can be used to evaluate the genetic effects of individual major genes (up to 2-3 major genes) and the collective genetic effects of polygenes as well as their heritability values. The present paper introduces the process of the establishment of the procedure, main achievements and application results. An example was given to illustrate the steps, methods and effectiveness of the procedure.

Crosses, Genetic↗
PubMed1998

[Population dynamics of the response of the genomic pattern of the mobile genetic element Dm412 in Drosophila on selection for a quantitative trait].

In an isogenic line of Drosophila melanogaster carrying the Mendelian mutation radius incompletus, selection for the total length of two segments of the disrupted longitudinal wing vein was conducted. After gamma-irradiation at a dose of 13 Gy, positive and negative truncation selection became highly effective and was completed in 50 generations. The pattern of mobile genetic element Dm412 was almost completely fixed in the course of selection. In the positive direction of selection, fixations of mobile genetic element (MGE) sites exceeded losses; in the negative direction, this relationship was reversed. The number of MGE sites in the pattern increased from 23 to 33 and to 26 in the positive and negative directions, respectively. The mean heterozygosity of MGE sites decreased respectively ten and six times. The dynamics of some sites (6F, 43B, 66A, 69E, and others) corresponded to that expected with an adaptive response to selection. Two out of these sites (43B and 66A) were previously assigned to hot sites of Dm412 transposition induced by heat shock. Fixation and loss of sites continued on average for tens of generations. Four hypotheses describe the relationship between patterns of polygenes and MGE in the context of explanation of the above facts: (1) genetic drift; (2) the linkage of MGE and polygenes without modification of the latter (hitchhiking); (3) the linkage and modifying effect of MGE on polygenes linked with them; (4) the selection of the "champion" pattern of polygenes and a random or adaptive MGE pattern linked with it. Hypotheses 1 and 2 are unlikely, hypothesis 3 is possible in the case of other selection modes, whereas hypothesis 4 seems to be most plausible.

Animals↗
PubMed2025

Prematurity and Genetic Liability for Autism Spectrum Disorder.

BACKGROUND: Autism Spectrum Disorder (ASD) is a neurodevelopmental condition characterized by diverse presentations and a strong genetic component. Environmental factors, such as prematurity, have also been linked to increased liability for ASD, though the interaction between genetic predisposition and prematurity remains unclear. This study aims to investigate the impact of genetic liability and preterm birth on ASD conditions. METHODS: We analyzed phenotype and genetic data from two large ASD cohorts, the Simons Foundation Powering Autism Research for Knowledge (SPARK) and Simons Simplex Collection (SSC), encompassing 78,559 individuals for phenotype analysis, 12,519 individuals with genome sequencing data, and 8,104 individuals with exome sequencing data. Statistical significance of differences in clinical measures was evaluated between individuals with different ASD and preterm status. We assessed the rare variants burden using generalized estimating equations (GEE) models and polygenic load using ASD-associated polygenic risk score (PRS). Furthermore, we developed a machine learning model to predict ASD in preterm children using phenotype and genetic features available at birth. RESULTS: Individuals with both preterm birth and ASD exhibit more severe phenotypic outcomes despite similar levels of genetic liability for ASD across the term and preterm groups. Notably, preterm ASD individuals showed an elevated rate of de novo variants identified in exome sequencing (GEE model, p=0.005) in comparison to the non-ASD preterm group. Additionally, a GEE model showed that a higher ASD PRS, preterm birth, and male sex were positively associated with a higher predicted probability for ASD, reaching a probability close to 90% in SPARK. Lastly, we developed a machine learning model using phenotype and genetic features available at birth with limited predictive power (AUROC = 0.65). CONCLUSIONS: Preterm birth may exacerbate the multimorbidity present in ASD, which was not due to the ASD genetic factors. However, increased genetic factors may elevate the likelihood of a preterm child being diagnosed with ASD. Additionally, a polygenic load of ASD-associated variants had an additive role with preterm birth in the predicted probability for ASD, especially for boys. We propose that incorporating genetic assessment into neonatal care could benefit early ASD identification and intervention for preterm infants.

Autism Spectrum Disorder↗
PubMed2026

Arrhythmia and cardiomyopathy risk in Taiwan with complementary biobank evidence on thyroid genetic susceptibility: an integrative population-based framework.

BACKGROUND: Arrhythmia-induced cardiomyopathy (AiCM) is a potentially reversible cause of ventricular dysfunction; however, only a subset of patients with arrhythmia develop cardiomyopathy. Emerging evidence suggests that endocrine factors, particularly thyroid dysfunction with genetic susceptibility, may contribute to inter-individual variability in arrhythmia-related myocardial outcomes. METHODS: We performed a dual-cohort population-based study using the National Health Insurance Research Database (NHIRD, 2000-2015) and the Taiwan Biobank (TWB). In NHIRD, we examined the association between newly diagnosed arrhythmia and incident cardiomyopathy using Cox proportional hazards models. In TWB, genome-wide data, thyroid-stimulating hormone (TSH), polygenic risk scores (PRSs), lifestyle factors, and metabolic comorbidities were analyzed using multivariable regression and interaction models to assess determinants of thyroid dysfunction. RESULTS: In the NHIRD cohort, arrhythmia was associated with a significantly increased risk of incident cardiomyopathy (adjusted hazard ratio (aHR): 2.49, 95% CI: 1.94-2.96), with atrial fibrillation showing the strongest association among arrhythmia subtypes. In the TWB cohort, a higher thyroid polygenic risk score was strongly associated with thyroid dysfunction (adjusted odds ratio (aOR): 6.64, 95% CI: 5.86-7.52). The association between genetic susceptibility and thyroid dysfunction was further modified by metabolic and lifestyle factors, including diabetes, hyperlipidemia, and dietary patterns. Genome-wide analysis identified multiple loci associated with thyroid-stimulating hormone regulation, consistent with a polygenic architecture of thyroid endocrine traits. CONCLUSION: Arrhythmia was associated with an increased risk of cardiomyopathy in a nationwide cohort, while thyroid genetic susceptibility was strongly associated with thyroid dysfunction in a biobank cohort and modified by metabolic and lifestyle factors. These findings provide complementary population-level evidence of parallel cardiovascular and endocrine-genetic associations. Because the two cohorts were not individually linked, causal inference cannot be established. The results support a systems-level framework of endocrine-cardiac interaction and suggest that integrated clinical and genetic risk assessment may help identify individuals who warrant closer monitoring.

arrhythmia↗
PubMed2025

Genomic and Developmental Models to Predict Cognitive and Adaptive Outcomes in Autistic Children.

IMPORTANCE: Although early signs of autism are often observed between 18 and 36 months of age, there is considerable uncertainty regarding future development. Clinicians lack predictive tools to identify those who will later be diagnosed with co-occurring intellectual disability (ID). OBJECTIVE: To predict ID in children diagnosed with autism. DESIGN, SETTING, AND PARTICIPANTS: This prognostic study involved the development and validation of models integrating genetic variants and developmental milestones to predict ID. Models were trained, cross-validated, and tested for generalizability across 3 autism cohorts: Simons Foundation Powering Autism Research (SPARK), Simons Simplex Collection, and MSSNG. Autistic participants were assessed older than 6 years of age for ID. Study data were analyzed from January 2023 to July 2024. EXPOSURES: Ages at attaining early developmental milestones, occurrence of language regression, polygenic scores for cognitive ability and autism, rare copy number variants, de novo loss-of-function and missense variants impacting constrained genes. MAIN OUTCOMES AND MEASURES: The out-of-sample performance of predictive models was assessed using the area under the receiver operating characteristic curve (AUROC), positive predictive values (PPVs), and negative predictive values (NPVs). RESULTS: A total of 5633 autistic participants (4574 male [81.2%]) were included in this analysis. On average, participants were diagnosed with autism at 4 (IQR, 3-7) years of age and assessed for ID at 11 (8-14) years of age, with 1159 participants (20.6%) being diagnosed with ID. The model integrating all predictors yielded an AUROC of 0.653 (95% CI, 0.625-0.681), and this predictive performance was cross-validated and generalized across cohorts. This modest performance reflected that only a subset of individuals carried large-effect variants, high polygenic scores, or presented delayed milestones. However, combinations of genetic variants that are typically not considered clinically relevant by diagnostic laboratories achieved PPVs of 55% and correctly identified 10% of individuals developing ID. The addition of polygenic scores to developmental milestones specifically improved NPVs rather than PPVs. Notably, the ability to stratify ID probabilities using genetic variants was up to 2-fold higher in individuals with delayed milestones compared with those with typical development. CONCLUSIONS AND RELEVANCE: Results of this prognostic study suggest that the growing number of neurodevelopmental condition-associated variants cannot, in most cases, be used alone for predicting ID. However, models combining different classes of variants with developmental milestones provide clinically relevant individual-level predictions that could be useful for targeting early interventions.

Humans↗
PubMed1981

Genetic transmission of serum IgE Levels.

Genetic aspects of IgE levels were studied in three large pedigrees, many of whose members had atopic sensitivities to ragweed. Data on 184 persons (80 M, 104 F) were analyzed by the methods of Elston and Stewart after logarithmic transformation and appropriate adjustment for sex and age effects. Several modes of transmission were fitted to the data. The environmental model (of equal transmission frequency for all genotypes) clearly did not fit the data (chi 2 23.03, df 3); this suggested a strong hereditary involvement in IgE distribution. High IgE levels being determined by a dominant allele gave the best fit among the hypotheses examined in pooled data. Under a pure polygenic model, the estimated heritability was 49.5%. Using a mixed model of major gene and polygenic transmission (in an analysis which approximates, but is biased toward inflating the major gene component) polygenic inheritance was found to be 11%, but has no significant improvement over the major gene model. When families are analyzed separately, there was evidence of significant heterogeneity among families. The genetic picture was blurred, with one family favoring recessive inheritance of high IgE levels, one with no clear mode, and the third leaning slightly in favor of dominant inheritance. This suggests that the mechanism is not as simple as was thought and that there may be either two alleles or one gene involved in the determination of IgE levels. The findings are consistent with IgE levels being genetically determined with heritability estimated to be about 50%.

Adolescent↗
PubMed1983

The genetics of quantitative plasma Lp(a): analysis of a large pedigree.

Likelihood analysis using the mixed model of quantitative plasma Lp(a) measurements on members of a large pedigree provided evidence that high levels of Lp(a) are inherited as a dominant major gene with polygenic background. The dominant allele frequency was estimated as 0.10. The major gene and polygenic components together accounted for 95% of the variation seen in the measurements. The major gene index and OBP plots, methods that do not allow for the presence of both components, favored the polygenic model over the major gene model as the mode of inheritance. No association was found with any of the lipids, lipoproteins or apolipoproteins considered.

Female↗
PubMed1993

Complex segregation analysis of antibodies to thyroid peroxidase in Old Order Amish families.

Autoimmune thyroid disease (AITD) may be characterized by the measurement in serum of antibodies to thyroid peroxidase. A population of Old Order Amish individuals and families was investigated to determine the prevalence of these antibodies and to examine hypotheses about the mode of transmission of thyroid antibodies. Complex segregation analyses were performed on 4 large multigenerational Old Order Amish families composed of 26 nuclear families containing 199 first degree relatives. Several alternative hypotheses of genetic transmission were examined. Hypotheses of no transmission, polygenic inheritance, single locus transmission, and mixed inheritance were compared. The analyses incorporated population prevalences obtained from a random sample of individuals. Results suggest that the pattern of transmission of thyroid antibodies in these families is consistent with a mixed model in which the major gene is transmitted in an autosomal dominant pattern. The mixed model postulates that there is a single gene of major effect as well as a polygenic component that can act separately and/or together to confer susceptibility for this phenotype. The parameter estimates for the major locus are: gene frequency (q), 0.16 +/- 0.01; maximum male penetrance, 0.35; and maximum female penetrance, 0.70. The heritability of the polygenic background is estimated at 0.41.

Adolescent↗
PubMed1978

A family study of two skeletal variants: atlas bridging and clinoid bridging.

The frequency of two non-metric skeletal traits, atlas bridging and clinoid bridging, were examined serially in a randomly chosen sample of 147 families who participated in the Burlington Growth Study. The sample is representative of an Ontario white Anglo-Saxon population. Partial and complete atlas briging occurred in 29.2% of the sample, partial and complete clinoid bridging in 15.2%. Atlas bridging appears at an average age of 10.7 years, clinoid bridging at seven years, demonstrating that these characters are not simply expressions of soft tissue sclerosis in old age. Both traits show no strong associations with bone robusticity although atlas bridging is slightly more frequent in males. Both traits are more frequent in relatives of affected individuals than in the sample as a whole. Correlations between parents and offspring and between sibs are highly significant for atlas bridging, less so far clinoid bridging. These traits should fit either a single gene or quasi-continuous, polygenic model of inheritance. Several tests for polygenic inheritance such as the correlation between first and second born sibs' trait condition, the relationship between trait expression in offspring and total trait incidence in affected parents, and the correlation between trait frequency and expressivity on an intergroup basis were all positive for atlas bridging. The evidence for polygenic inheritance of clinoid bridging is weaker but suggestive. The results obtained in this study for atlas bridging are comparable to data from one earlier family study. The evidence suggests that these two traits should prove useful as genetic markers in skeletal population studies although there is still need for careful control over trait observation and description. Future research should attempt to measure non-metric traits continuously when their underlying distributions are known to be graded.

Adult↗
PubMed1987

A family study of dermatoglyphic traits in India: segregation analysis of accessory palmar triradii and the atd angle.

Accessory triradii and the atd angle were examined via complex segregation analysis in order to evaluate possible genetic effects on these dermatoglyphic traits, measured in an endogamous Brahmin caste of peninsular India. The phenotypes considered included: presence of accessory palmar triradii a' and d', associated with the interdigital areas II and IV, respectively; presence of an accessory axial triradius tt' associated with the proximal margin of the palm; and an arctanh-transformation of the atd angle measurement. For all accessory triradii considered in the present investigation familial resemblance was evident. The most parsimonious model which could account for the observed resemblance was a multifactorial model that includes polygenic effects as well as transmissible environmental effects that are inherited in the same pattern as polygenes. Evidence of familial resemblance was also found for the arctanh-transformed atd angle, which could be attributed, initially, to both a major effect and a multifactorial component. Tests of transmission of a putative major gene were performed which yielded results consistent with Mendelian transmission, although an alternative test of no transmission of the major effect also fit the data. In light of these contrasting results we are precluded from accepting with confidence the notion of a major gene influence on the atd angle. We have concluded that the accessory triradii a', d', and tt', and the atd angle are influenced by multifactorial effects, including additive polygenes and possible environmental factors, such as intrauterine effects.

Dermatoglyphics↗
PubMed1989

Complex segregation analysis of dental morphological variants.

A set of 20 morphological variants of the dental crowns and four characteristics of the jaws are tested for probable mode of inheritance using the complex segregation analysis method of Morton et al. (Am. J. Hum. Genet. 23:602-611, 1971). Models tested include three two-allele single-locus models (dominant, codominant, and recessive) and a model employing the polychotomized normal distribution of liability (an additive polygenic model), with transmissibility estimated via maximum likelihood. Most of the traits studied are observed using ordinal scales with several grades, and many are tested using more than one dichotomy of their scale. These multiple analyses allow for an examination of such factors as trait incidence on the results of the statistical analysis. The results of the analysis yield propositions of major genes for 13 of the 24 traits examined. Two traits give good evidence of being polygenic in origin. The remaining nine characters present methodological problems that do not allow for a definite conclusion on their mode of inheritance at this time. The ability to test varying levels of transmissibility in the polygenic model allows for an estimation of the percentage of trait variance determined by familial factors. Estimates of transmissibility for all characters examined range from 0 to 1, with a mean of 0.36. These findings may suggest a large environmental role in the development of dental crown morphology. However, the possibility exists that difficulties in the ability to classify the expression of certain traits consistently result in overestimates of the environmental influences on the development of those characters.

Anthropology, Physical↗
PubMed1995

Segregation analysis of plasma lipoprotein(a) levels in pedigrees with molecularly defined familial hypercholesterolemia.

The role of genetic and environmental factors in determining the variability in plasma lipoprotein(a) [Lp(a)] levels was investigated in 220 members of 14 families with familial hypercholesterolemia (FH) whose plasma Lp(a) levels were previously reported [Leitersdorf et al. (1991) J Lipid Res 32:1513-1519]. One hundred four subjects harbored a mutant low density lipoprotein (LDL) receptor allele as confirmed by the identification of the specific mutations in addition to the haplotype analysis reported before. Four different mutant alleles were identified, each in a defined genetic group--Druze, Christian-Arabs, Ashkenazi, and Sepharidic Jews. Sex- and age-adjusted mean plasma Lp(a) levels were significantly higher in FH family members (34.0 mg/dl) than in non-FH family members (21.1 mg/dl). Lp(a) levels were further adjusted for lipid levels and apo(a) isoforms. A mixture of two normal distributions fitted the adjusted Lp(a) levels better than did a single normal distribution. Segregation analysis indicated that a major effect of a non-transmitted environmental factor explained the mixture of distributions in addition to polygenic loci which influenced Lp(a) levels within each distribution. The major environmental factor and the polygenic loci accounted for 45% and 20% of the adjusted Lp(a) variation, respectively. Furthermore, sex, age, lipid levels, apo(a) isoform, the major environmental effect, and the unmeasured polygenes could account for 80% of the unadjusted variation of plasma Lp(a) in these families.

Adolescent↗
PubMed1992

Familiality and partitioning the variability of femoral bone mineral density in women of child-bearing age.

The contributions of polygenic loci and environmental factors to femoral bone mineral density (BMD) in g/cm2) variability were estimated in modified family sets consisting of women of child-bearing age. Femoral BMDs were measured in 535 women who were members of 137 family sets consisting minimally of an index, her sister, and unrelated female control. The family set could also include multiple sisters and first cousins. Women included in these family sets were all between 20 and 40 years of age to minimize the cohort effects of maturation and menopause on measures of BMD. BMDs were measured at three femoral sites using dual photon densitometry. Values were regressed on age and Quetelet Index which explained 13-15% of the variability in BMD (dependent on site). Subsequent variance components analysis on the residuals indicated that unmeasured polygenic loci accounted for substantial additional variability: 67% for femoral neck, 58% for Wards triangle, and 45% for trochanter. These results suggest that polygenic loci account for approximately half of the variability in maximal femoral BMD.

Adult↗
PubMed2004

A large-sample QTL study in mice: I. Growth.

By use of long-term selection lines for high and low growth, a large-sample (n = approximately 1,000 F2) experiment was conducted in mice to further understand the genetic architecture of complex polygenic traits. In combination with previous work, we conclude that QTL analysis has reinforced classic polygenic paradigms put in place prior to molecular analysis. Composite interval mapping revealed large numbers of QTL for growth traits with an exponential distribution of magnitudes of effects and validated theoretical expectations regarding gene action. Of particular significance, large effects were detected on Chromosome (Chr) 2. Regions on Chrs 1, 3, 6, 10, 11, and 17 also harbor loci with significant contributions to phenotypic variation for growth. Despite the large sample size, average confidence intervals of approximately 20 cM exhibit the poor resolution for initial estimates of QTL location. Analysis with genome-wide and chromosomal polygenic models revealed that, under certain assumptions, large fractions of the genome may contribute little to phenotypic variation for growth. Only a few epistatic interactions among detected QTL, little statistical support for gender-specific QTL, and significant age effects on genetic architecture were other primary observations from this study.

Animals↗
PubMed1996

Production of congenic mouse strains carrying genomic intervals containing SLE-susceptibility genes derived from the SLE-prone NZM2410 strain.

Systemic lupus erythematosus is inherited as a complex polygenic trait. Four genomic intervals containing major SLE-susceptibility loci were previously identified by interval mapping in the NZM2410 mouse model. In this paper, we utilized a marker-assisted selection protocol to produce four congenic mouse strains, each carrying an NZM2410-derived SLE-susceptibility interval on a C57BL/6-resistant background. Each strain carries only one susceptibility allele derived from this polygenic model and consequently can be used to characterize the specific component phenotypes contributed by individual SLE-susceptibility genes. We illustrate the efficacy of this approach with phenotypic data for one of our congenic strains, B6.NZMH2(z). Our results indicate that this single genomic interval from Chromosome (Chr) 17 of NZM2410 can mediate increased levels of IgG autoantibodies specific for chromatin and that, similar to results obtained in our original genetic cross, B6.NZMH2(z/b) heterozygotes are more prone than B6.NZMH2(z) homozygotes to the development of humoral autoimmunity to nuclear antigens. These results illustrate the feasibility of using congenic strains to dissect the complex pathogenic mechanisms that mediate polygenic SLE. These congenic strains will be valuable tools in the genetic analysis of SLE susceptibility. In future studies, these congenic strains will be interbred to produce bi- and tri-congenic strains in order to assess the role of genetic interactions in the expression of specific components of SLE pathogenesis. They will also be instrumental to the positional cloning and identification of the genes responsible for SLE susceptibility, via the production of congenic recombinants.

Animals↗
PubMed1998

Familial clustering of rheumatoid arthritis with other autoimmune diseases.

Previous studies have shown that rheumatoid arthritis aggregates within families. However, no formal genetic analysis of rheumatoid arthritis in pedigrees together with other autoimmune diseases has been reported. We hypothesized that there are genetic factors in common in rheumatoid arthritis and other autoimmune diseases. Results of odds-ratio regression and complex segregation analysis in a sample of 43 Caucasian pedigrees ascertained through a rheumatoid arthritis proband or matched control proband, revealed a very strong genetic influence on the occurrence of both rheumatoid arthritis and other autoimmune diseases. In an analysis of rheumatoid arthritis alone, only one inter-class measure, parent-sibling, resulted in positive evidence of aggregation. However, three inter-class measures (parent-sibling, sibling-offspring, and parent-offspring pairs) showed significant evidence of familial aggregation with odds-ratio regression analysis of rheumatoid arthritis together with all other autoimmune diseases. Segregation analysis of rheumatoid arthritis alone revealed that the mixed model, including both polygenic and major gene components, was the most parsimonious. Similarly, segregation analysis of rheumatoid arthritis together with other autoimmune diseases revealed that a mixed model fitted the data significantly better than either major gene or polygenic models. These results were consistent with a previous study which concluded that several genes, including one with a major effect, is responsible for rheumatoid arthritis in families. Our data showed that this conclusion also held when the phenotype was defined as rheumatoid arthritis and/or other autoimmune diseases, suggesting that several major autoimmune diseases result from pleiotropic effects of a single major gene on a polygenic background.

Adult↗