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PubMed2026

Refining the link between REM sleep behavior disorder and neurodegeneration: Genetic correlation, Mendelian randomization, and colocalization evidence.

Observational studies have proposed a link between isolated rapid eye movement sleep behavior disorder (iRBD) and several neurodegenerative diseases. We employed genome-wide linkage disequilibrium score regression (LDSC), standard two-sample Mendelian randomization (MR), and colocalization analysis to assess the causal links between iRBD and these neurodegenerative conditions. iRBD demonstrated a positive causal association with Alzheimer disease (odds ratio [OR] = 1.02, 95% confidence interval [CI]: 1.00-1.03, P = 1.10E-02), Parkinson disease (OR = 1.10, 95% CI: 1.03-1.16, P = 2.96E-03), and multiple sclerosis (OR = 1.09, 95% CI: 1.02-1.17, P = 1.61E-02). A strong positive genetic correlation with dementia with Lewy bodies was observed (rg = 1.6313, P = .0002), along with a causal association (OR = 1.45, 95% CI: 1.03-2.06, P = 3.53E-02), further supported by colocalization analysis. No significant causal relationship was identified between iRBD and amyotrophic lateral sclerosis (all P > .05). Additionally, reverse Mendelian randomization analyses did not reveal any causal relationships between the neurodegenerative diseases studied and iRBD. Our findings provide robust genetic evidence supporting a causal relationship between iRBD and the risk of multiple neurodegenerative diseases, highlighting the potential for shared pathophysiological mechanisms.

Humans↗
PubMed1989

[Problem of typological differentiation of the defect in symptom-poor schizophrenia (clinico-genetic correlations)].

The clinico-genealogical method with the use of a genetic-mathematic analysis was applied to examine 85 probands with pure-symptoms schizophrenia (221 relations of grade I kinship). Schizophrenia with the defect of the simple deficiency type was established to be genetically, similar to schizophrenia with a psychopath-like defect characterized by veschroben. Different types of familial predisposition by the type of schizophrenia+ and by the spectrum of psychopathies were found to correspond to the studied variants of pure-symptoms schizophrenia. These correlations were confirmed by the data of the genetic-correlation analysis. It is assumed that determination of the typological differences in the defect structure in pure-symptoms schizophrenia is under the control of constitutional and genetic factors.

Adult↗
PubMed2004

Genetic correlation between melanization and antibacterial immune responses in a natural population of the malaria vector Anopheles gambiae.

The immune system of invertebrates can mount different responses, including melanotic encapsulation and several antibacterial defense mechanisms. Variation of the efficacies of these responses is generally considered to be a product of the evolutionary pressure on each response due to infection by parasites. However, potential interactions and trade-offs among the different responses of the immune system could constrain the evolutionary potential of each response. In a natural population of the mosquito Anopheles gambiae, we measured the genetic association between the melanization response and an antibacterial response in two environmental qualities (well-fed and undernourished larvae). In both environments the two immune responses were positively genetically correlated: in full-sib families that were most likely to melanize a bead, injected bacteria were most likely to be cleared. Thus, our data do not support the idea of a trade-off among different outcomes of the invertebrate immune system, but rather that some families are overall immunologically superior to others.

Analysis of Variance↗
PubMed2005

No detectable genetic correlation between male and female mating frequency in the stalk-eyed fly Cyrtodiopsis dalmanni.

There is much interest in explaining why female insects mate multiply. Females of the stalk-eyed fly Cyrtodiopsis dalmanni can mate several times each day in a lifetime which may span several months. There are many adaptive explanations, but one hypothesis that has received little rigorous empirical attention is that female multiple mating has evolved for non-adaptive reasons as a correlated response to selection for high male mating frequency rather than because of direct or indirect benefits accruing to females. We tested this hypothesis in stalk-eyed flies by measuring the mating frequency of females from lines that exhibited a direct response in males to artificial selection for increased ('high') and decreased ('low') male mating frequency. We found that the mating frequency of high-line females did not differ from that of low-line females. Hence, there was no support for a genetic correlation between male and female mating frequency in this species. Our study suggests that the genes which influence remating may not be the same in the sexes, and that females remate frequently in this species to gain as yet unidentified benefits.

Analysis of Variance↗
PubMed2002

A genetic correlation between age at pupation and melanization immune response of the yellow fever mosquito Aedes aegypti.

To investigate the evolutionary cost of an immune response, we selected six lines of the mosquito Aedes aegypti for earlier or later pupation and measured the extent to which this selection procedure changed the mosquito's ability to encapsulate and melanize a negatively charged Sephadex bead. After 10 generations of selection, the age at pupation in the two selection regimes differed by about 0.7 days, accompanied by an increase of wing length of the mosquitoes selected for late pupation. Among the mosquitoes that had been selected for early pupation, only 6% had strongly or completely melanized the bead, while among the individuals that had been selected for late pupation, 32% had melanized the bead. Thus, our results suggest a genetic correlation between age at pupation and immunocompetence. As a consequence, mosquitoes that respond to increased intense parasite pressure with more effective immunity are predicted to pay for the increased defense with slower development.

Aedes↗
PubMed2003

Genetic correlates of gene expression in recombinant inbred strains: a relational model system to explore neurobehavioral phenotypes.

Full genome sequencing, high-density genotyping, expanding sets of microarray assays, and systematic phenotyping of neuroanatomical and behavioral traits are producing a wealth of data on the mouse central nervous system (CNS). These disparate resources are still poorly integrated. One solution is to acquire these data using a common reference population of isogenic lines of mice, providing a point of integration between the data types. Recombinant inbred (RI) mice, derived through inbreeding of progeny from an inbred cross, are a powerful tool for complex trait mapping and analysis of the challenging phenotypes of neuroscientific interest. These isogenic RI lines are a retrievable genetic resource that can be repeatedly studied using a wide variety of assays. Diverse data sets can be related through fixed and known genomes, using tools such as the interactive web-based system for complex trait analysis, www.WebQTL.org. In this report, we demonstrate the use of WebQTL to explore complex interactions among a wide variety of traits--from mRNA transcripts to the impressive behavioral and pharmacological variation among RI strains. The relational approach exploiting a common set of strains facilitates study of multiple effects of single genes (pleiotropy) without a priori hypotheses required. Here we demonstrate the power of this technique through genetic correlation of gene expression with a database of neurobehavioral phenotypes collected in these strains of mice through more than 20 years of experimentation. By repeatedly studying the same panel of mice, early data can be re-examined in light of technological advances unforeseen at the time of their initial collection.

Animals↗
PubMed1989

Heritabilities of and genetic correlations among six health problems in Holstein cows.

Information from 7712 lactations of Holstein dairy cows was collected from 33 commercial herds around Ithaca, NY in the 3 yr from 1981 to 1983. The data were divided into subsets corresponding to lactation 1, lactation 2, and lactation 3 or greater. To estimate heritabilities of dystocia, retained placenta, metritis, ovarian cysts, milk fever, and mastitis, a mixed linear model (herd-year fixed and sire random effects) with 0 or 1 as the observed response was used. Variance components were estimated using Henderson's Method 3. The results show moderate heritabilities (.15 to .40) for dystocia, metritis, milk fever, and mastitis and low heritability (less than .12) for retained placenta and cystic ovaries. Genetic correlations between dystocia, retained placenta, metritis, and mastitis were moderate in size and positive, whereas cystic ovaries were correlated negatively with dystocia and retained placenta. A general reproductive health trait (dystocia, retained placenta, metritis, cystic ovaries, and milk fever combined in one trait) also was analyzed. The estimated heritability of this trait was .21, .11, and .00 for first calf heifers, second lactation cows, and older cows, respectively.

Animals↗
PubMed2001

Negative genetic correlation for adult fitness between sexes reveals ontogenetic conflict in Drosophila.

Because of their distinctive roles in reproduction, females and males are selected toward different optimal phenotypes. Ontogenetic conflict between the sexes arises when homologous traits are selected in different directions. The evolution of sexual dimorphism by sex-limited gene expression alleviates this problem. However, because the majority of genes are not sex-limited, the potential for substantial conflict may remain. Here we assess the degree of ontogenetic conflict in the fruit-fly, Drosophila melanogaster, by cloning 40 haploid genomes and measuring their Darwinian fitness in both sexes. The intersexual genetic correlations for juvenile viability, adult reproductive success, and total fitness were used to gauge potential conflict during development. First, as juveniles, where the fitness objectives of the two sexes appear to be similar, survival was strongly positively correlated across sexes. Second, after adult maturation, where gender roles diverge, a significant negative correlation for reproductive success was found. Finally, because of counterbalancing correlations in the juvenile and adult components, no intersexual correlation for total fitness was found. Highly significant genotype-by-gender interaction variance was measured for both adult and total fitness. These results demonstrate strong intersexual discord during development because of the expression of sexually antagonistic variation.

Adaptation, Physiological↗
PubMed1994

Heritabilities and phenotypic and genetic correlations for bovine postrigor calpastatin activity, intramuscular fat content, Warner-Bratzler shear force, retail product yield, and growth rate.

To estimate the heritability (h2) of postrigor calpastatin activity (CA), 555 steers were reared and processed conventionally. Breed-types included purebreds (Angus [A], Braunvieh [B], Charolais [C], Gelbvieh [G], Hereford [H], Limousin [L], Pinzgauer [P], Red Poll [RP], and Simmental [S]), composite populations (MARC I [1/4 C, 1/4 B, 1/4 L, 1/8 H, 1/8 A], MARC II [1/4 S, 1/4 G, 1/4 H, 1/4 A], and MARC III [1/4 RP, 1/4 H, 1/4 P, 1/4 A]), and F1 crosses (H, A, C, G, P, Shorthorn, Galloway, Longhorn, Nellore, Piedmontese, or Salers x H or A). Steers were serially slaughtered on an age-constant (across breed groups) basis. Heritability estimates for CA, i.m. fat content (IMF), Warner-Bratzler shear (WBS) force, retail product yield (RPY), and ADG were .65 +/- .19, .93 +/- .02, .53 +/- .15, .45 +/- .18, and .32 +/- .26, respectively. The genetic correlations (rg) of CA with WBS, RPY, and ADG were .50 +/- .22, .44 +/- .25, and -.52 +/- .37, respectively. The rg of IMF with WBS, RPY, and ADG were -.57 +/- .16, -.63 +/- .15, and -.04 +/- .11, respectively. These h2 and rg estimates indicate that it should be possible to select for improvements in CA, IMF, and WBS. However, selection against CA may be a more suitable approach for improving meat tenderness than selection for increased IMF because the level of genetic antagonism between CA and RPY was not as great as that between IMF and RPY.

Adipose Tissue↗
PubMed1992

Estimation of direct and maternal heritability and genetic correlation for backfat and growth rate in swine using data from centrally tested Yorkshire boars.

The purpose of this study was to estimate components of variance and covariance for backfat and growth rate in swine tested in central test stations in the United States. Data were collected from 26 central boar test stations from 1984 through 1990. The traits analyzed were backfat adjusted to a 104.5-kg basis and ADG adjusted to a 36-kg on-test weight. Records from 7,951 purebred Yorkshire boars were analyzed. Contemporary groups were defined as boars of a breed that were tested and sold as a common group in a test station. Variance components were estimated using a pseudo-expectation method with a multiple-trait, sire-maternal grandsire model. Direct heritabilities for backfat and ADG were estimated to be .56 and .24, respectively. Direct maternal effects were significant for both backfat and ADG; they accounted for 11 and 23% of the variance, respectively. The additive genetic correlation between backfat and ADG was approximately zero. Within this population of centrally tested Yorkshire boars, heritability seems to be high for backfat and moderate for ADG, with a significant maternal effect on each trait.

Adipose Tissue↗
PubMed2005

Changing definition of productive life in US Holsteins: effect on genetic correlations.

Data included 392,800 records for cows born between 1995 and 1997. Traits analyzed were milk, fat, and protein yields, somatic cell score, days open (DO), 18 linear type traits, final score, and several measures of longevity. Productive life (PL) was defined as the total number of days in milk up to 84 mo of age with a restriction of 305, 500, or 999 d per lactation (PL(305), PL(500), or PL(999), respectively). Herd life was defined as the total number of days from the first calving date to the last (culling) date. A multiple-trait sire model including the effects of registration status, herd-year, age group, month of calving and stage of lactation, sire, and residual was used for parameter estimation. The average duration of the first lactation was 365 d for survivors and 386 d for culled cows. Lactation lengths for the survivors in the next 3 parities all exceeded 330 d. Heritability estimates of between 0.08 and 0.10 were obtained for all definitions of longevity. As maximum recordable PL was increased from 305 to 999 d per lactation, the genetic correlations with milk production increased (from -0.11 to +0.14) and with DO decreased (-0.62 to -0.27). Formulas for an indirect prediction of PL from correlated traits were developed. As maximum PL per lactation was increased, little change in the weights used to predict the various measures of PL, with the exception of DO was found. As the currently used value of PL(305) does not properly account for the longer lactation lengths that are routinely occurring with today's cows, PL with longer lactations may be preferable in routine evaluation.

Animals↗
PubMed1991

Age adjustment factors, heritabilities and genetic correlations for scrotal circumference and related growth traits in Hereford and Brangus bulls.

Field data records on 10,511 Hereford and 2,522 Brangus bulls between 330 and 430 d of age were analyzed to find age of calf and age of dam adjustment factors for yearling scrotal circumference. Age of calf adjustment factors were .024 cm/d for Hereford bulls and .041 cm/d for Brangus bulls. Sons of Hereford dams were adjusted to a 6- to 8-yr dam age basis by adding .7, .3, .2, .2 or .3 cm for dams 2, 3, 4, 5 or 8 or more years old, respectively. Age of dam adjustment factors for Brangus bulls were .8, .4, .3 and .2 for dams 2, 3, 4 or 8 or more years old, respectively. Variance and covariance components for yearling scrotal circumference and several growth traits were estimated within breed using multiple-trait models and pseudo expectations involving the solutions and the right-hand sides of the mixed-model equations. Additive heritability estimates for yearling scrotal circumference of .53 and .16 were found for Hereford and Brangus bulls, respectively. Maternal heritability estimates of .12 and .10 were found for Hereford and Brangus bulls, respectively. Genetic correlations between yearling scrotal circumference and other growth traits were positive for both sets of data indicating that selection for yearling scrotal circumference should not adversely affect other growth traits in either breed. Environmental correlation estimates between yearling scrotal circumference and adjusted birth weight and between yearling scrotal circumference and adjusted 205-d weight and adjusted 365-d height were positive and moderate in magnitude for both breeds.

Age Factors↗
PubMed1987

Estimates of heritability for plasma very low density lipoprotein concentration and genetic correlations with lipid content, body volume, and density in Coturnix coturnix japonica.

Genetic parameters associated with very low density lipoprotein concentration (VLDL) in a randombred population of Coturnix were estimated. Associated traits were: body density, volume, and weight of the live bird, and lipid content of the whole carcass. A total of 739 progeny by 50 sires and 126 dams was the basis of the data. The VLDL was highly heritable (.52) and highly correlated with lipid content (greater than .50) but correlated to lesser degrees with body density (.24) and body volume (.20). The genetic correlation estimates between VLDL and body weight were small relative to their standard errors.

Adipose Tissue↗
PubMed1991

Heritabilities and genetic correlations for postweaning growth and feed intake of beef bulls and steers.

Data from studies conducted at Miles City, MT and Lethbridge, AB were pooled to evaluate genetic and environmental variation in feed intake (MEI), growth rate (ADG), MEI-to-gain ratio (M/G), final weight (FWT), and fat thickness (FAT). A total of 124 sires with an average of 4.25 progeny each were represented in the data. Restricted maximum likelihood methods were used to estimate within and between paternal half-sib estimates of variance and covariance. Heritabilities and genetic, phenotypic, and environmental correlations with inference to populations at 365 d of age were calculated from the estimates. Heritabilities were as follows: ADG, .38 +/- .16; MEI, .45 +/- .17; M/G, .26 +/- .15; FWT .25 +/- .15; and FAT .52 +/- .17. The genetic correlation of MEI with ADG was large (.73 +/- .13) and antagonistic to genetic improvement of M/G through selection for ADG. Efficient genetic improvement in M/G was found to depend on using either MEI or an indicator of composition of gain as selection criteria in addition to ADG. Selection to improve M/G using an index that included FWT and FAT, in addition to MEI and ADG, resulted in greater predicted response in ADG and lesser predicted response in MEI than the index of ADG and MEI alone.

Adipose Tissue↗
PubMed1994

Heritabilities and genetic correlations of conformation and plumage characteristics in pheasant (Phasianus colchicus).

Data were obtained from 588 pedigreed pheasants of an unselected population. Body weight, shank length (SL), plumage measurements, and plumage score were analyzed to estimate heritabilities and genetic and phenotypic correlations. All measurements were made at 28 and 120 d of age. The h2 estimates (sire component) were the following: .27 and .30 for BW at 28 (BW28) and at 120 d (BW120), respectively; .34 and .79 for SL at 28 (SL28) and at 120 d (SL120), respectively; .30 and .13 for rectrices length (RL) at 28 (RL28) and at 120 d (RL120), respectively; .14 for primary remex at 28 d (PR); .21 for primary remex 1 at 28 d (PR1); .23 for secondary remiges length (SRL); .34 for body weight gain (BWG); .35 for shank length gain (SLG). Negative genetic correlations between BW and SL with plumage traits at 120 d were found. The magnitude of heritability indicates that selection for BW is possible but the negative association with plumage traits must be carefully considered. The improvement of housing conditions could lead to birds with a well-developed plumage, because environment influenced variability of plumage traits.

Analysis of Variance↗
PubMed1999

Heritability of nociception II. 'Types' of nociception revealed by genetic correlation analysis.

Clinical pain syndromes, and experimental assays of nociception, are differentially affected by manipulations such as drug administration and exposure to environmental stress. This suggests that there are different 'types' of pain. We exploited genetic differences among inbred strains of mice in an attempt to define these primary 'types'; that is, to identify the fundamental parameters of pain processing. Eleven randomly-chosen inbred mouse strains were tested for their basal sensitivity on 12 common measures of nociception. These measures provided for a range of different nociceptive dimensions including noxious stimulus modality, location, duration and etiology, among others. Since individual members of inbred strains are identical at all genetic loci, the observation of correlated strain means in any given pair of nociceptive assays is an index of genetic correlation between these assays, and hence an indication of common physiological mediation. Obtained correlation matrices were subjected to multivariate analyses to identify constellations of nociceptive assays with common genetic mediation. This analysis revealed three major clusters of nociception: (1) baseline thermal nociception, (2) spontaneously-emitted responses to chemical stimuli, and (3) baseline mechanical sensitivity and cutaneous hypersensitivity. Many other nociceptive parameters that might a priori have been considered closely related proved to be genetically divergent.

Animals↗
PubMedDate not supplied

MRI and genetic correlates of cognitive function in elders with memory impairment.

The present study investigated the relationship between genetic variation, MRI measurements and neuropsychological function in a sample of 58 elders exhibiting memory decline. In agreement with previous reports, we found that the epsilon4 allele of the apolipoprotein E (APOE) and the D allele of the angiotensin converting enzyme (ACE) polymorphisms negatively modulated the cognitive performance. Further, we found an association between the A allele of the apolipoprotein C1 (APOC1) polymorphism and poorer memory and frontal lobe function. No clear associations emerged between MRI measures of white matter lesions (WML) or hippocampal sulcal cavities (HSC) and the cognitive performance after controlling for age effects. Further, the degree of WML or HSC lesions was in general not predisposed genetically except for the presence of the A allele of the APOC1 polymorphism that was related to a higher severity of HSC scores. Our results suggest that WML or HSC do not represent important brain correlates of genetic influences on cognitive performance in memory impaired subjects.

Aged↗