Contribution Of Additive Genetic Effects Research Articles

Genome-wide Association Meta-analysis of Childhood and Adolescent Internalizing Symptoms.

To investigate the genetic architecture of internalizing symptoms in childhood and adolescence. In 22 cohorts, multiple univariate genome-wide association studies (GWASs) were performed using repeated assessments of internalizing symptoms, in a total of 64,561 children and adolescents between 3 and 18 years of age. Results were aggregated in meta-analyses that accounted for sample overlap, first using all available data, and then using subsets of measurements grouped by rater, age, and instrument. The meta-analysis of overall internalizing symptoms (INToverall) detected no genome-wide significant hits and showed low single nucleotide polymorphism (SNP) heritability (1.66%, 95% CI= 0.84-2.48%, neffective= 132,260). Stratified analyses indicated rater-based heterogeneity in genetic effects, with self-reported internalizing symptoms showing the highest heritability (5.63%, 95% CI= 3.08%-8.18%). The contribution of additive genetic effects on internalizing symptoms appeared to be stable over age, with overlapping estimates of SNP heritability from early childhood to adolescence. Genetic correlations were observed with adult anxiety, depression, and the well-being spectrum (|rg| > 0.70), as well as with insomnia, loneliness, attention-deficit/hyperactivity disorder, autism, and childhood aggression (range |rg|= 0.42-0.60), whereas there were no robust associations with schizophrenia, bipolar disorder, obsessive-compulsive disorder, or anorexia nervosa. Genetic correlations indicate that childhood and adolescent internalizing symptoms share substantial genetic vulnerabilities with adult internalizing disorders and other childhood psychiatric traits, which could partially explain both the persistence of internalizing symptoms over time and the high comorbidity among childhood psychiatric traits. Reducing phenotypic heterogeneity in childhood samples will be key in paving the way to future GWAS success.

Actigraphic sleep and cortisol in middle childhood: A multivariate behavioral genetics model

To date, behavioral genetic studies investigated either sleep or cortisol levels in middle childhood, but not both simultaneously. Therefore, a pertinent question is the degree to which genetic factors and environmental factor contribute to the correlation between sleep and cortisol levels. To address this question, we employed the classical twin design. We measured sleep in 6-9-year-old twins (N = 436 twin pairs, “Together Unique” study) over four consecutive nights using actigraphy, and we measured morning cortisol on two consecutive days. Sleep duration, sleep efficiency, and wake episodes were used as indicators of sleep. Morning cortisol level was used as cortisol indicator. A structural equation model was fitted to estimate the contribution of additive genetic effects (A), shared (common) environmental effects, (C) and unique environmental effects (E) to phenotypic variances and covariances. Age, cohort, and sex were included as covariates. The heritability of sleep duration, sleep efficiency, and wake episodes were 52%, 45%, and 55%, respectively. Common environmental factors played no significant role. High genetic correlations between sleep duration and sleep efficiency and high genetic correlations between sleep efficiency and wake episodes were found. Shared environmental (29%) and unique environmental factors (53%) explained the variance in morning cortisol levels. Because the sleep and cortisol measures were found to be uncorrelated, we did not consider genetic and environmental contributions to the association between the sleep and cortisol measures. Our findings indicate that sleep duration, sleep efficiency, and wake episodes in children are mostly impacted by genetic factors and by unique environmental factors (including measurement error).

Inheritance of pre-emergent metribuzin tolerance and putative gene discovery through high-throughput SNP array in wheat (Triticum aestivum L.)

BackgroundHerbicide tolerance is an important trait that allows effective weed management in wheat crops in dryland farming. Genetic knowledge of metribuzin tolerance in wheat is needed to develop new cultivars for the industry. Here, we investigated gene effects for metribuzin tolerance in nine crosses of wheat by partitioning the means and variances of six basic generations from each cross into their genetic components to assess the gene action governing the inheritance of this trait. Metribuzin tolerance was measured by a visual senescence score 21 days after treatment. The wheat 90 K iSelect SNP genotyping assay was used to identify the distribution of alleles at SNP sites in tolerant and susceptible groups.ResultsThe scaling and joint-scaling tests indicated that the inheritance of metribuzin tolerance in wheat was adequately described by the additive-dominance model, with additive gene action the most significant factor for tolerance. The potence ratio for all the crosses ranged between − 1 and + 1 for senescence under metribuzin-treated conditions indicating a semi-dominant gene action in the inheritance of metribuzin tolerance in wheat. The number of segregating genes governing metribuzin tolerance was estimated between 3 and 15. The consistent high heritability range (0.82 to 0.92) in F5–7 generations of Chuan Mai 25 (tolerant) × Ritchie (susceptible) cross indicated a significant contribution of additive genetic effects to metribuzin tolerance in wheat. Several genes related to photosynthesis (e.g. photosynthesis system II assembly factor YCF48), metabolic detoxification of xenobiotics and cell growth and development (cytochrome P450, glutathione S-transferase, glycosyltransferase, ATP-binding cassette transporters and glutathione peroxidase) were identified on different chromosomes (2A, 2D, 3B, 4A, 4B, 7A, 7B, 7D) governing metribuzin tolerance.ConclusionsThe simple additive–dominance gene effects for metribuzin tolerance will help breeders to select tolerant lines in early generations and the identified genes may guide the development of functional markers for metribuzin tolerance.

Inheritance and combining ability studies for yield and yield-attributing traits of crossing big and curly fruit lines in chili (Capsicum annuum L.)

Big and curly fruit lines of Capsicum annuum L. were crossed according to Griffing’s Method (Diallel) Method 1. The objectives of this paper were to show the assessment of the general combining ability (GCA) and specific combining ability (SCA) of C. annuum L. lines through diallelic crosses providing information about the genetic effect, heritability and heterosis on expression of yield and yield component traits. Thirty cross combination and six parents were evaluated in a randomized complete block design with three replications. The experiment was conducted at Leuwikopo experiment field, Department of Agronomy and Horticulture, Faculty of Agriculture, Bogor Agricultural University on October 2012 to April 2013. The GCA and SCA means square were significant for all traits. The higher values of mean squares associated to GCA indicates a strong contribution of additive genetic effects to the expression of some traits. C5 scored highly for GCA in some traits and can be used to develop an open pollinated variety. Estimates of heritability showed that some of the traits were highly heritable, and weight per plant trait should readily be improved by selection. The SCA of cross C2 × C5, C5 × C120, C19 × C120, C120 × C159 were found to be high, with progeny showing high positive heterosis for some traits, thereby indicating that those crosses have the potential to function as a superior cultivar within commercial breeding programmes.

Genetic architecture underlying host choice differentiation in the sympatric host races of Lochmaea capreae leaf beetles.

Speciation in herbivorous insects has received considerable attention during the last few decades. Much of this group's diversity originates from adaptive population divergence onto different host plants, which often involves the evolution of specialized patterns of host choice behaviour. Differences in host choice often translates directly into divergence in mating sites, and therefore positive assortative mating will be created which will act as a strong barrier to gene flow. In this study, we first explored whether host choice is a genetically determined trait in the sympatric willow and birch host races of the leaf feeding beetle Lochmaea capreae, or whether larval experience influences adult host choice. Once we had established that host choice is a genetically based trait we determined its genetic architecture. To achieve this, we employed a reciprocal transplant design in which offspring from pure willow and birch cross-types, F1, F2 and backcrosses were raised on each host plant and their preference was determined upon reaching adulthood. We then applied joint-scaling analysis to uncover the genetic architecture of host preference. Our results suggest that rearing host does not have a pronounced effect on adult's host choice; rather the segregation pattern implies the existence of genetic loci affecting host choice in these host races. The joint-scaling analysis revealed that population differences in host choice are mainly influenced by the contribution of additive genetic effects and also maternally inherited cytoplasmic effects. We explore the implications of our findings for evolutionary dynamics of sympatric host race formation and speciation.

Prevalence of and familial influences on purging disorder in a community sample of female twins.

Purging disorder (PD) was recently included as an otherwise specified feeding or eating disorder (OSFED) in the DSM-5; however, limited information is available on its prevalence, and its etiology is unknown. Data from 1,790 monozygotic and 1,440 dizygotic European American female twins (age range = 18-29 years) from the Missouri Adolescent Female Twin Study were used to investigate prevalence and familial influences for PD. A structured clinical interview assessed lifetime DSM-IV criteria for eating disorders and PD. After adjustment for age, twin correlations and biometrical twin models were used to estimate familial (i.e., genetic plus shared environmental) influences on PD. One hundred and twenty one (3.77%; 95% CI: 3.14, 4.49) women met criteria for lifetime PD. Twin correlations suggested that genetic, shared environmental, and nonshared environmental factors influenced liability to PD. Nonshared environmental factors accounted for 56% [35%, 79%] of the variance in PD. Although familial effects accounted for a significant proportion of variance (44% [21%, 65%]), it was not possible to disentangle the independent contributions of additive genetic effects (20% [0%, 65%]) and shared environmental effects (24% [0%, 57%]). PD is a prevalent form of eating pathology. Familial factors are relevant to the development of PD but do not demonstrate the magnitude of heritable factors found for other eating disorders.

Half‐Sib Matting and Genetic Analysis of Agronomic, Morphological, and Physiological Traits in Sainfoin under Nonstressed versus Water‐Deficit Conditions

ABSTRACTHalf‐sib matting, including polycross and openpollination, are powerful methods to obtain quantitative genetic information in breeding of forage plants. In sainfoin (Onobrychis viciifolia Scop).no prior efforts have been made to estimate the genetic parameters of traits and comparing these methods. Thirty half‐sib families (16 polycross and 14 open‐pollinated families) were evaluated under two moisture environments (nonstressed and water deficit) during 2010 to 2012. Water deficit decreased plant height (20.3%), plant density (51.8%), dry matter yield (45–53%), relative water content (RWC) (18.9%) and increased carotenoid content (23.9%), proline content (65.7%), specific catalase (74.4%) and ascorbate peroxidase activity (52.7%). High genotypic variation was observed for most of the measured traits. Narrow‐sense heritability (h2PFM) estimates for agro‐morphological traits ranged from 0.42 (leaf to stem ratio) to 0.95 (flowering date). The highest and lowest h2PFM among physiological traits were estimated for carotenoid content (0.50) and RWC (0.83), respectively. Moderate to high heritability for most traits showed the contribution of additive genetic effects suggesting phenotypic selection could be successful. The best agromorphological and physiological traits (such as plant height, plant density, dry matter yield, and RWC) under water deficit belonged to families 16 and 27. Dry matter yield had significant and positive correlation with plant height and plant density indicating indirect selection would also be effective to improve forage yield. Principal component analysis separated polycross and open‐pollinated families into distinct groups. Open‐pollinated families had higher mean values and general combining ability for most of the traits while polycross families had higher heritability and genetic gain from selection. This may indicate a more effective selection and a higher genetic advance in polycross families.

Intracortical Bone Remodeling Variation Shows Strong Genetic Effects

Intracortical microstructure influences crack propagation and arrest within bone cortex. Genetic variation in intracortical remodeling may contribute to mechanical integrity and, therefore, fracture risk. Our aim was to determine the degree to which normal population-level variation in intracortical microstructure is due to genetic variation. We examined right femurs from 101 baboons (74 females, 27 males; aged 7–33 years) from a single, extended pedigree to determine osteon number, osteon area (On.Ar), haversian canal area, osteon population density, percent osteonal bone (%On.B), wall thickness (W.Th), and cortical porosity (Ct.Po). Through evaluation of the covariance in intracortical properties between pairs of relatives, we quantified the contribution of additive genetic effects (heritability [h 2]) to variation in these traits using a variance decomposition approach. Significant age and sex effects account for 9 % (Ct.Po) to 21 % (W.Th) of intracortical microstructural variation. After accounting for age and sex, significant genetic effects are evident for On.Ar (h 2 = 0.79, p = 0.002), %On.B (h 2 = 0.82, p = 0.003), and W.Th (h 2 = 0.61, p = 0.013), indicating that 61–82 % of the residual variation (after accounting for age and sex effects) is due to additive genetic effects. This corresponds to 48–75 % of the total phenotypic variance. Our results demonstrate that normal, population-level variation in cortical microstructure is significantly influenced by genes. As a critical mediator of crack behavior in bone cortex, intracortical microstructural variation provides another mechanism through which genetic variation may affect fracture risk.

Heritability variations of body linearity and obesity indicators during growth

Longitudinal as well as cross-sectional studies have shown variations with age in heritability estimates for body dimensions from infancy to adulthood, even though the patterns of variation are not completely clear. Further study on this subject is of great interest and may help obesity interventions for preventing or treating obesity in children. Therefore, the aim of the present study is to analyse the changes in the genetic and environmental architecture of 8 body linearity and obesity-related phenotypes during the growth process in a cross-sectional sample of 1018 nuclear families from the province of Biscay (Basque Country, Spain). The contribution of additive genetic effects to the variation of the analysed traits was estimated by a variance component analysis using the SOLAR program. Moderate to high heritability estimates were obtained for all 8 anthropometric phenotypes (38.23–65.98%). The heritability values show an increasing trend with age and in the course of the entire ontogenetic development two age periods were remarkable. At 7+–8+ years of age a strong increase in heritability estimates was found for all the anthropometric phenotypes, except for the sum of skinfolds (SF6), reflecting the biological significance of genes during mid-childhood. During puberty, most of the obesity related phenotypes showed their highest heritability values while linear measurements and weight presented a decrease in the genetic contributions. In conclusion, this study confirms that additive genetic influences have a considerable effect on body linearity and obesity-related traits throughout the growth period and that mid-childhood and puberty are very sensitive periods in human life cycle.

Combining ability for grain chemistry quality traits in a white oat diallelic cross

There has been a strong demand for oat genotypes that contain caryopsis with high chemical quality which can suit the different market niches. Therefore, the objectives of this study were to assess the general (GCA) and specific combining ability (SCA) of white oat cultivars through diallelic crosses providing information about the genetic effects on expression of grain chemical quality components. Also, it was aimed to estimate the heterosis on F1 and F2 generations and the vigor loss due to inbreeding. During 2008, 21 hybrid populations F1 and F2 were obtained from artificial crossing among seven Brazilian white oat cultivars, following the complete diallel design, without considering the reciprocals. These populations and their parents were evaluated in the 2009 season in the experimental field in Capao do Leao, RS, Brazil. The higher values of mean squares associated to GCA indicates a strong contribution of additive genetic effects to the expression of grain chemical components. The parents tested showed a tendency to develop progeny with negative heterosis regarding protein, lipid, β-glucan and soluble dietary fiber in the grain, and positive for the content of nitrogen-free extract, total and insoluble dietary fiber. IAC 7 features a potential parent for obtaining grains with high protein and dietary fiber content, and low caloric content, fit to human diet. Meanwhile, UPF 15 and FAPA Louise can represent donors of alleles to increase lipid contents, while FAPA Louise and URS Guapa can be used to raise the grain nitrogen-free extract contents of lines intended for animal feeding.

Genetic and Environmental Factors Shape Infant Sleep Patterns: A Study of 18-Month-Old Twins

Between 25% and 30% of children and adolescents experience sleep disorders. These disorders are complex phenotypes that are regulated by many genes, the environment, and gene-environment interactions. The objective of this study was to evaluate the contribution of genetic and environmental factors to sleep behaviors in early childhood and to contribute to the knowledge on appropriate therapeutic approaches, using a twin design. Data on sleeping behavior were collected from 314 18-month-old twin pairs (127 monozygotic and 187 dizygotic)using a parent-rated questionnaire. We used structural equation modeling to estimate genetic and environmental variance components for different sleep behaviors (cosleeping, sleep duration, and night awakenings). Shared environment explained almost all (98.3%) of the total variance in cosleeping. Sleep duration was substantially influenced by shared environmental factors (64.1% nocturnal sleep and 61.2% diurnal sleep), with a moderate contribution of additive genetic effects (30.8% and 36.3% for nocturnal and diurnal sleep, respectively). For nocturnal waking episodes, we found a shared environmental contribution of 63.2% and a heritability estimate of 35.3%. Most sleep disturbances during early childhood are explained by common shared environmental factors, and behavioral interventions adopted by parents and focused on modifying sleep behavior could contribute to solving sleep disturbances in this age group. However, the influence of genetic factors should not be underestimated, and research in this area could clarify the physiologic architecture of sleeping and contribute to selecting appropriate personalized therapeutic approaches.

Twin Analyses of Fatigue

Prolonged fatigue equal to or greater than 1 month duration and chronic fatigue equal to or greater than 6 months duration are both commonly seen in clinical practice, yet little is known about the etiology or epidemiology of either symptom. Chronic fatigue syndrome (CFS), while rarer, presents similar challenges in determining cause and epidemiology. Twin studies can be useful in elucidating genetic and environmental influences on fatigue and CFS. The goal of this article was to use biometrical structural equation twin modeling to examine genetic and environmental influences on fatigue, and to investigate whether these influences varied by gender. A total of 1042 monozygotic (MZ) twin pairs and 828 dizygotic (DZ) twin pairs who had completed the University of Washington Twin Registry survey were assessed for three fatigue-related variables: prolonged fatigue, chronic fatigue, and CFS. Structural equation twin modeling was used to determine the relative contributions of additive genetic effects, shared environmental effects, and individual-specific environmental effects to the 3 fatigue conditions. In women, tetrachoric correlations were similar for MZ and DZ pairs for prolonged and chronic fatigue, but not for CFS. In men, however, the correlations for prolonged and chronic fatigue were higher in MZ pairs than in DZ pairs. About half the variance for both prolonged and chronic fatigue in males was due to genetic effects, and half due to individual-specific environmental effects. For females, most variance was due to individual environmental effects.

Genome‐wide Scan of Plasma Cholecystokinin in Baboons Shows Linkage to Human Chromosome 17

Cholecystokinin (CCK) is known to inhibit food intake and is an important signal for controlling meal volume, indicating a possible role in weight regulation. Our objective was to investigate genetic influences on plasma CCK in baboons. Subjects were 376 baboons (males = 113, females = 263) from the Southwest National Primate Research Center, housed at the Southwest Foundation for Biomedical Research, San Antonio, Texas. Anthropometric and biochemical parameters were analyzed. Genetic effects on plasma CCK were estimated by the maximum likelihood-based variance components method implemented in the software program SOLAR (Sequential Oligogenic Linkage Analysis Routines). Male baboons (32.7 +/- 6 kg) were much heavier than females (20.2 +/- 4 kg). Similarly, mean (+/- standard deviation) plasma CCK values were also higher in male baboons (13.8 +/- 6 pM) than female baboons (12.5 +/- 4 pM). Significant heritabilities were observed for plasma CCK (0.14 +/- 0.1, p < 0.05), body weight (h2 = 0.62 +/- 0.15, p < 10(-8)), and glucose (h2 = 0.68 +/- 0.17, p < 10(-7)). A genome-wide scan of plasma CCK detected a strong signal for a quantitative trait locus (QTL) on chromosome 17p12-13 [logarithm of the odds (LOD) = 3.1] near marker D17S804. Suggestive evidence of a second QTL was observed on chromosome 4q34-35 (LOD = 2.3) near marker D4S2374. A substantial contribution of additive genetic effects to the variation in plasma levels of CCK was demonstrated in baboons. The identification of a QTL for plasma CCK on chromosome 17p is significant, as several obesity-related traits such as BMI, leptin, adiponectin, and acylation stimulating protein have already been mapped to this region.

Gaining New Insights into How Genetic Factors Influence Human Dental Development by Studying Twins

Many previous attempts to quantify the contribution of genetic factors to human dental variation using the classical twin design have been based on untested assumptions that lead to unreliable estimates of heritability. We have applied structural equation modelling to several different dental phenotypes in a sample of over 600 pairs of Australian twins, enabling the goodness-of-fit of the data to be tested against genetic models incorporating different components of genetic and environmental variance. Our results indicate that the contribution of additive genetic effects to phenotypic variation differs considerably between different dental traits. Heritability estimates for intercuspal distances of molar teeth and for incisal overbite and overjet are low to moderate in magnitude, whereas heritabilities for overall molar crown size and arch dimensions are moderate to high. We propose that after formation of the enamel knots during odontogenesis, the emerging pattern of molar cusps results from a cascade of local epigenetic events, rather than being under direct genetic control. Variation in molar crown size is explained best by a model incorporating additive genetic effects, as well as environmental influences that are both unique and common to co-twins. These environmental influences presumably operate in utero during the early stages of molar odontogenesis prior to crown calcification. The relatively low heritabilities noted for occlusal traits are consistent with the importance of masticatory activity and muscle function in determining the interrelationships between teeth in opposing dental arches. We believe that well-designed studies of twins, coupled with modern genome-scanning approaches, offer great potential to identify key “dental” genes and to clarify how these genes interact with the environment during development.

Twin studies of eating disorders: A review

Objective Twin methodology has been used to delineate etiological factors in many medical disorders and behavioral traits including eating disorders. Although twin studies are powerful tools, their methodology can be arcane and their implications easily misinterpreted. Method The goals of this study are to (a) review the theoretical rationale for twin studies; (b) provide a framework for their interpretation and evaluation; (c) review extant twin studies on eating disorders; and (d) explore the implications for understanding etiological issues in eating disorders. Discussion On the basis of this review, it is not possible to draw firm conclusions regarding the precise contribution of genetic and environmental factors to anorexia nervosa. Twin studies confirm that bulimia nervosa is familial and reveal significant contributions of additive genetic effects and of unique environmental factors in liability to bulimia nervosa. The magnitude of the contribution of shared environment is less clear, but in the studies with the greatest statistical power, it appears to be less prominent than additive genetic factors. © 2000 by John Wiley & Sons, Inc. Int J Eat Disord 27: 1–20, 2000.

Twin studies of eating disorders: a review.

Twin methodology has been used to delineate etiological factors in many medical disorders and behavioral traits including eating disorders. Although twin studies are powerful tools, their methodology can be arcane and their implications easily misinterpreted. The goals of this study are to (a) review the theoretical rationale for twin studies; (b) provide a framework for their interpretation and evaluation; (c) review extant twin studies on eating disorders; and (d) explore the implications for understanding etiological issues in eating disorders. On the basis of this review, it is not possible to draw firm conclusions regarding the precise contribution of genetic and environmental factors to anorexia nervosa. Twin studies confirm that bulimia nervosa is familial and reveal significant contributions of additive genetic effects and of unique environmental factors in liability to bulimia nervosa. The magnitude of the contribution of shared environment is less clear, but in the studies with the greatest statistical power, it appears to be less prominent than additive genetic factors.

Body weight in the Finnish Twin Cohort

We estimated genetic and environmental variance of BMI among 7245 non-pregnant MZ and DZ pairs of the same sex from the population-based Finnish Twin Cohort. The contributions of additive genetic effects, shared and non-shared environmental effects on age-adjusted BMI-variance were estimated by LISREL structural equation models. Genetic effects contribute 72% in men and 66.4% in non-pregnant women of total variance, while 27.8% of variance among men and 33.6% among women is due to non-shared environmental effects. Shared environmental effects were nonsignificant (0% for women and 0.2% for men). Similar values were obtained for hereditary and non-shared environmental effects, when shared environmental effects were not included in the model. The inclusion of pregnant women did not substantially change heritability estimates.