Specific Genetic Effects Research Articles

Mixed Linear Model Approaches of Association Mapping for Complex Traits Based on Omics Variants.

Precise prediction for genetic architecture of complex traits is impeded by the limited understanding on genetic effects of complex traits, especially on gene-by-gene (GxG) and gene-by-environment (GxE) interaction. In the past decades, an explosion of high throughput technologies enables omics studies at multiple levels (such as genomics, transcriptomics, proteomics, and metabolomics). The analyses of large omics data, especially two-loci interaction analysis, are very time intensive. Integrating the diverse omics data and environmental effects in the analyses also remain challenges. We proposed mixed linear model approaches using GPU (Graphic Processing Unit) computation to simultaneously dissect various genetic effects. Analyses can be performed for estimating genetic main effects, GxG epistasis effects, and GxE environment interaction effects on large-scale omics data for complex traits, and for estimating heritability of specific genetic effects. Both mouse data analyses and Monte Carlo simulations demonstrated that genetic effects and environment interaction effects could be unbiasedly estimated with high statistical power by using the proposed approaches.

Heritability of Biomarkers of Oxidized Lipoproteins: Twin Pair Study.

To determine whether biomarkers of oxidized lipoproteins are genetically determined. Lipoprotein(a) (Lp[a]) is a heritable risk factor and carrier of oxidized phospholipids (OxPL). We measured oxidized phospholipids on apolipoprotein B-containing lipoproteins (OxPL-apoB), Lp(a), IgG, and IgM autoantibodies to malondialdehyde-modified low-density lipoprotein, copper oxidized low-density lipoprotein, and apoB-immune complexes in 386 monozygotic and dizygotic twins to estimate trait heritability (h(2)) and determine specific genetic effects among traits. A genome-wide linkage study followed by genetic association was performed. The h(2) (scale: 0-1) for Lp(a) was 0.91±0.01 and for OxPL-apoB 0.87±0.02, which were higher than physiological, inflammatory, or lipid traits. h(2) of IgM malondialdehyde-modified low-density lipoprotein, copper oxidized low-density lipoprotein, and apoB-immune complexes were 0.69±0.04, 0.67±0.05, and 0.80±0.03, respectively, and for IgG malondialdehyde-modified low-density lipoprotein, copper oxidized low-density lipoprotein, and apoB-immune complexes 0.62±0.05, 0.52±0.06, and 0.53±0.06, respectively. There was an inverse correlation between the major apo(a) isoform and OxPL-apoB (R=-0.49; P<0.001) and Lp(a) (R=-0.48; P<0.001) and OxPL-apoB was modestly correlated with Lp(a) (ρ=0.57; P<0.0001). The correlation in major apo(a) isoform size was concordant (R=1.0; P<0.001) among monozygotic twins but not dizygotic twins (R=0.40; P=0.055). Lp(a) and OxPL-apoB shared genetic codetermination (genetic covariance, ρG=0.774±0.032; P=1.09×10(-38)), although not environmental determination (environmental covariance, ρE=0.081±0.15; P=0.15). In contrast, Lp(a) shared environmental but not genetic codetermination with autoantibodies to malondialdehyde-modified low-density lipoprotein and copper oxidized low-density lipoprotein, and apoB-immune complexes. Sib-pair genetic linkage of the Lp(a) trait revealed that single nucleotide polymorphism rs10455872 was significantly associated with OxPL-apoB after adjusting for Lp(a). OxPL-apoB and other biomarkers of oxidized lipoproteins are highly heritable cardiovascular risk factors that suggest novel genetic origins of atherothrombosis.

SLC6A4 markers modulate platelet 5-HT level and specific behaviors of autism: A study from an Indian population

Presence of platelet hyperserotonemia and effective amelioration of behavioral dysfunctions by selective serotonin reuptake inhibitors (SSRI) in autism spectrum disorders (ASD) indicate that irregularities in serotonin (5-HT) reuptake and its homeostasis could be the basis of behavioral impairments in ASD patients. SLC6A4, the gene encoding serotonin transporter (SERT) is considered as a potential susceptibility gene for ASD, since it is a quantitative trait locus for blood 5-HT levels. Three functional polymorphisms, 5-HTTLPR, STin2 and 3'UTR-SNP of SLC6A4 are extensively studied for possible association with the disorder, with inconclusive outcome. In the present study, we investigated association of these polymorphisms with platelet 5-HT content and symptoms severity as revealed by childhood autism rating scale in ASD children from an Indian population. Higher 5-HT level observed in ASD was highly significant in children with heterozygous and homozygous genotypes comprising of minor alleles of the markers. Quantitative transmission disequilibrium test demonstrated significant genetic effect of STin2 allele as well as STin2/3'UTR-SNP and 5-HTTLPR/3'UTR-SNP haplotypes on 5-HT levels, but no direct association with overall CARS score and ASD phenotype. Significant genetic effect of the markers on specific behavioral phenotypes was observed for various sub-phenotypes of CARS in quantitative trait analysis. Even though the 5-HT level was not associated with severity of behavioral CARS score, a significant negative relationship was observed for 5-HT levels and level and consistency of intellectual response and general impression in ASD children. Population-based study revealed higher distribution of the haplotype 10/G of STin2/3'UTR-SNP in male controls, suggesting protective effect of this haplotype in male cases. Overall results of the study suggest that SLC6A4 markers have specific genetic effect on individual ASD behavioral attributes, might be through the modulation of 5-HT content.

Contrast effects and sex influence maternal and self-report dimensional measures of attention-deficit hyperactivity disorder.

The heritability of attention-deficit/hyperactivity disorder (ADHD) is higher for children than adults. This may be due to increasing importance of environment in symptom variation, measurement inaccuracy when two raters report behavior of a twin-pair, a contrast effect resulting from parental comparison of siblings and/or dimensionality of measures. We examine rater contrast and sex effects in ADHD subtypes using a dimensional scale and compare the aetiology of self, versus maternal-report. Data were collected using the Strengths and Weaknesses of ADHD and Normal Behaviour Scale (SWAN): maternal-report for 3,223 twins and siblings (mean age 21.2, SD=6.3) and self-report for 1,617 twins and siblings (mean age 25.5, SD=3.2). Contrast effects and magnitude of genetic and environmental contributions to variance of ADHD phenotypes (inattention, hyperactivity-impulsivity, combined behaviours) were examined using structural equation modeling. Contrast effects were evident for maternal-report hyperactivity-impulsivity (b=-0.04) and self-report inattention (-0.09) and combined ADHD (-0.08). Dominant genetic effects were shared by raters for inattention, hyperactivity-impulsivity and combined ADHD. Broad-sense heritability was equal across sex for maternal-report inattention, hyperactivity-impulsivity and combined ADHD (0.72, 0.83, 0.80). Heritability for corresponding subtypes in self-reported data were best represented by sex (0.46, 0.30, 0.39 for males; 0.69, 0.41, 0.65 for females). Heritability difference between maternal and self-report ADHD was due to greater variance of male specific environment in self-report data. Self-reported ADHD differed across sex by magnitude of specific environment and genetic effects.

Epigenetics of multiple sclerosis

Multiple sclerosis (MS) is a complex disease characterized by autoimmune demyelination of the myelin sheath of the central nervous system. Varying degrees of disability result from disruptions in neural, physical, and psychological processes. No clear cause of MS has been identified, but specific genetic mutations and environmental effects have been established as factors in disease development. However, the low disease concordance rates and transmission disequilibrium observed in MS prevent genetic factors alone from explaining increased susceptibility. As a result, the involvement of epigenetics, or heritable changes in the genome that are not caused by alterations in the underlying DNA sequence, has been proposed to resolve these apparent discrepancies. This article focuses on recent research into three primary epigenetic mechanisms and their relation to MS susceptibility: DNA methylation, histone modifications, and post-transcriptional regulation of target genes by microRNA. These epigenetic phenomena interact with each other and environmental stimuli to produce disease. Promising experimental research has revealed that inhibitors of such epigenetic activity reduce disease phenotypes in animal models. In this article, ways in which epigenetic changes can induce MS development are described and prospective research avenues are proposed.&#x0D; &#x0D; Keywords: epigenetics; multiple sclerosis (MS); DNA methylation; histones; microRNA (miRNA)

Variation of Vitamin D in Cow’s Milk and Interaction with β-Lactoglobulin

Vitamin D is the collective name for a group of closely related lipids, whose main biological function is to maintain serum calcium and phosphorus concentrations within the normal range by enhancing the efficiency of the small intestine to absorb these minerals from the diet. We used a commercially available ELISA method for the determination of vitamin D in bovine milk. Individual milk samples from two different Italian Friesian herds were analysed. The enzyme immunoassay method used was confirmed as a useful tool to measure the vitamin D in the milk as it greatly reduces the time required to perform the conventional HPLC analysis. An interesting variation was found among individual animals that may be associated with management factors and specific genetic effects. A relationship was highlighted between vitamin D and the genetic polymorphism of β-lactoglobulin, the main bovine whey protein which is involved in the transport of small hydrophobic molecules such as retinol and vitamin D. The relatively high content of vitamin D in most milk samples suggests an opportunity to improve the natural content of vitamin D in milk either by acting on the herd management or selecting individuals genetically predisposed to produce milk with a higher vitamin D content.

Abstract P157: Does Physical Activity Modify the Association of 15 Well-established Obesity Loci with BMI: The ARIC Study

This study investigates gene-by-physical activity interaction with 15 well-replicated body mass index (BMI) loci in the Atherosclerosis Risk in Communities (ARIC) Study, a prospective, multi-center, bi-racial population-based cohort of adults (N=15,792 at baseline (1987-1989), aged 45-64). Our analyses were restricted to subjects of self-reported European descent with complete genotype and phenotype data (n=8059, 53% female, mean age 54.3 (SD 5.7)). BMI was computed from measured height and weight. Physical activity (PA) was measured using a modified validated Baecke questionnaire, resulting in an ordinal score ranging from 1.00-10.00 for sport and leisure-time activity. Physical activity was dichotomized at the sex-specific median for high/low PA, with high PA as the referent. BMI was regressed on single nucleotide polymorphism (SNP), PA level, SNP*PA level, and study-specific covariates assuming an additive genetic model. To account for multiple testing, interaction p-values less than 0.006 (0.10/15) were considered statistically significant. Mean BMI was 27.0 (SD 4.8) kg/m2, and sports and leisure time physical activity was 5.00 (SD 1.13, range 1.75-9.25) units. We replicated the main effects of SNP on BMI for FTO (rs9939609, p=8.52E-11) and SEC16B/RASAL2 (rs10913469, p=0.001), and NEGR1 was borderline significant (rs2815752, p=0.006). MAF was the only SNP that displayed a directionally inconsistent effect estimate with earlier findings (Beta: -0.02, SE -0.16, 0.13). Four of the interactions had a p-value &lt;0.1, including SEC16B, PTER, NEGR1, and SH2B1. The largest magnitude effect estimates among the nominally significant interactions were observed for SNPs rs10913469 (locus SEC16B/RASAL2, frequency: 0.2024) and rs10508503 (locus PTER, frequency: 0.0871). For rs10913469, each additional copy of the risk allele resulted in an increased BMI of 0.58 kg/m2 for those in the low PA category, but an increase of only 0.07 kg/m2 for those in the high PA category (p-interaction=0.007). For rs10508503, each additional copy of the risk allele resulted in an increased BMI of 0.51 kg/m2 for those in the low PA category, and a decreased BMI of 0.14 kg/m2 for those in the high PA category (p-interaction=0.013). Mean BMIs for those in the low physical activity category increase with additional copies of the C (risk) allele (mean BMI for TT=25.6, TC=27.2, CC=27.6 kg/m2, p=0.04), while mean BMIs of those with high PA do not differ between genotypes (mean BMI for TT=26.7, TC=26.8, CC=26.6 kg/m2, p=0.51). While we found a significant main effect of the SEC16B/RASAL2 SNP on BMI (p=0.001), for the PTER SNP we did not (p=0.229). These novel findings demonstrate the importance of context specific genetic effects and contribute to the growing literature highlighting the possible importance of physical activity in the attenuation of underlying genetic risk.

Statistical approaches in QTL mapping and molecular breeding for complex traits

Most of the important agronomic traits in crops, such as yield and quality, are complex traits affected by multiple genes with gene × gene interaction as well as gene × environment interaction. Understanding the genetic architecture of complex traits is a long-term task for quantitative geneticists and plant breeders who wish to design efficient breeding programs. Conventionally, the genetic properties of traits can be revealed by partitioning the total variation into variation components caused by specific genetic effects. With recent advances in molecular genotyping and high-throughput technology, the unraveling of the genetic architecture of complex traits by analyzing quantitative trait locus (QTL) has become possible. The improvement of complex traits has also been achieved by pyramiding individual QTL. In this review, we describe some statistical methods for QTL mapping that can be used to analyze QTL × QTL interaction and QTL × environment interaction, and discuss their applications in crop breeding for complex traits.

Increased familiarity of intellectual deficits in early-onset schizophrenia spectrum disorders

Objectives. Early-onset schizophrenia is considered to be neurobiologically similar to adult-onset forms, although it represents a more severe expression of the disorder. In the present study, we explored putative larger familial vulnerability of intellectual impairments in early-onset schizophrenia spectrum disorders (EOS) when compared to adult-onset (AOS) families. Methods. A sample of 340 subjects including schizophrenia spectrum disorder patients, their first degree relatives and age-matched healthy controls was assessed on intelligence quotient (IQ). We used linear regression analysis and intraclass correlation coefficients (ICC) to explore familial aggregation of IQ across age at onset groups. Results. The relationship between IQ level of patients and their first-degree relatives showed positive linear association (β = 0.43, P < 0.01). High significant familial aggregation was found for intelligence quotient in EOS families (ICC = 0.618, P < 0.01), while AOS families responded to lower estimates (ICC = 0.204, P = 0.26; between ICC comparison z = 1.993, P < 0.05). Conclusions. High aggregation of intellectual performance in the EOS group suggests larger familial vulnerability in early-onset forms of the disease when cognitive functions are considered. Within a continuum of psychopathology in schizophrenia spectrum disorders, specific genetic effects are discussed for distinct onset forms that might be in line with a neurodevelopmental model of the disease.

A Multivariate Twin Study of Obsessive-Compulsive Symptom Dimensions

Obsessive-compulsive disorder (OCD) is clinically heterogeneous, but it is unclear whether this phenotypic heterogeneity reflects distinct, or partially distinct, etiologic mechanisms. To clarify the structure of the genetic and environmental risk factors for the major symptom dimensions of OCD. Self-report questionnaires and multivariate twin model fitting. General community. A total of 4355 female members of the TwinsUK adult twin register. Scores on the Obsessive-Compulsive Inventory-Revised and 5 of its subscales (checking, hoarding, obsessing, ordering, and washing). A common pathway model did not fit the data well, indicating that no single latent factor can explain the heterogeneity of OCD. The best-fit multivariate twin model was an independent pathway model, whereby both common and unique genetic and/or environmental factors contribute to the etiology of each symptom dimension. The hoarding dimension had the lowest loading on the common factor and was more influenced by specific genetic effects (54.5% specific). With the exception of hoarding, most of the genetic variance was due to shared genetic factors (ranging from 62.5% to 100%), whereas most of the nonshared environmental variance was due to dimension-specific factors. Obsessive-compulsive disorder is unlikely to be an etiologically homogeneous condition. There is substantial etiologic overlap across the different OC symptom dimensions, but dimension-specific genetic, and particularly nonshared environmental, factors are at least as important. Hoarding shares the least amount of genetic liability with the remaining symptom dimensions. The results have implications for the current deliberations regarding OCD and the inclusion of a putative hoarding disorder in DSM-5.

The major histocompatibility complex and multiple sclerosis: a smoking gun?

There are many theories on the aetiology of multiple sclerosis but most lack much in the way of direct experimental support. Despite overwhelming evidence that the pathogenesis involves an interplay between genetic and environmental effects, progress in identifying the relevant risk factors has been painfully slow and there is practically no understanding about how these might interact and result in disease. In this issue, Hedstrom et al . (2011) present an integration of a specific genetic and environmental effect. In a case ( n = 843) control ( n = 1209) study carefully designed to reduce potential confounding, they consider established genetic factors (DRB1 and HLA-A) in the context of smoking; and find evidence that the effects on susceptibility attributable to these genetic loci are amplified by this lifestyle exposure. On the basis of this observation, and by analogy with established pathogenic mechanisms in rheumatoid arthritis (Karlson et al ., 2010), they argue that the post-translational modification of lung proteins caused by smoking might lead to multiple sclerosis in genetically susceptible individuals by priming circulating lymphocytes against cross-reacting CNS antigens. This is an intriguing hypothesis, which if confirmed would represent a major step forward in our understanding. Attempting to unravel the pathogenesis of any complex trait through association analysis is a perilous exercise, littered with traps for the unwary. Past experience has shown that researchers using this approach need to pay obsessional attention to detail if they are to avoid adding to the enormous literature confidently describing what turn out to be false positive associations (Ioannidis, 2005). At face value nothing could be simpler than establishing the relevance of an exposure by identifying a difference in its frequency between cases and controls. In this deceptively straightforward paradigm, establishing statistical significance appears to be the most challenging issue; and simultaneously avoiding confounding due to systematic …

Neurotransmitter and Neuromodulator Genes Associated With a History of Depressive Symptoms in Individuals With Alcohol Dependence

Depressive symptoms are common among individuals with alcohol use disorders and impact treatment outcome. Substantial overlap exists among the neurobiological systems proposed in the pathophysiology of depressive and alcohol use disorders; however, specific genetic effects contributing to risk for depressive comorbidity remain poorly understood. This study examines the association of depressive symptom scores for lifetime depression (the sum of DSM-IV major depression co-endorsed criteria for lifetime depression) with markers in 120 candidate genes in 554 alcohol-dependent individuals. The candidate genes code for molecules involved in dopamine, serotonin, glutamate, gamma-aminobutyric acid (GABA), and opioid neurotransmission, cell signaling, pharmacokinetics, stress biology, and behavioral control. Analyses were conducted at the single marker level with experimentwise permutation to control for multiple testing. Results revealed nominal associations for markers in 20 genes. Following experimentwise permutation, markers in the corticotropin-releasing hormone-binding protein (CRHBP) the μ-opioid receptor (OPRM1) and the β1 subunit of GABA A (GABA(A)) receptors (GABRB1) met or exceeded the significance threshold. None of the markers associated with depressive symptom scores were significantly associated with alcohol dependence symptom scores. These findings suggest potential risk genes for depressive symptoms in alcohol-dependent individuals.

A twin study of autism symptoms in Sweden

This study aimed to identify empirically the number of factors underlying autism symptoms-social impairments, communication impairments, and restricted repetitive behaviors and interests-when assessed in a general population sample. It also investigated to what extent these autism symptoms are caused by the same or different genetic and environmental influences. Autistic symptoms were assessed in a population-based twin cohort of >12,000 (9- and 12-year-old) children by parental interviews. Confirmatory factor analyses, principal component analyses and multivariate structural equation model fitting were carried out. A multiple factor solution was suggested, with nearly all analyses pointing to a three-factor model for both boys and girls and at both ages. A common pathway twin model fit the data best, which showed that there were some underlying common genetic and environmental influences across the different autism dimensions, but also significant specific genetic effects on each symptom type. These results suggest that the autism triad consists of three partly independent dimensions when assessed in the general population, and that these different autism symptoms, to a considerable extent, have partly separate genetic influences. These findings may explain the large number of children who do not meet current criteria for autism but who show some autism symptoms. Molecular genetic research may benefit from taking a symptom-specific approach to finding genes associated with autism.

Familial Transmission and Heritability of Childhood Disruptive Disorders

There is substantial evidence of a link between parental substance use disorders and antisocial behavior and childhood disruptive disorders in offspring, but it is unclear whether this transmission is specific to particular disorders or if a general liability accounts for familial resemblance. The authors examined whether the association between parental externalizing disorders and childhood disruptive disorders in preadolescent offspring is a result of the transmission of general or disorder-specific liabilities and estimated the genetic and environmental contributions to variation in these general and specific liability indicators. Participants were 1,069 families consisting of 11-year-old twins and their biological mother and father. Structural equation modeling was used to simultaneously estimate the general and specific transmission effects of four parental externalizing disorders (conduct disorder, adult antisocial behavior, alcohol dependence, and drug dependence) on childhood disruptive disorders (attention deficit hyperactivity disorder, conduct disorder, and oppositional defiant disorder). Parent-child resemblance was accounted for by the transmission of a general liability to externalizing disorders, and this general liability was highly heritable. Specific effects were also detected, but for sibling rather than parental transmission. Specific genetic and nonshared environmental effects were detected for each childhood disruptive disorder, but only conduct disorder exhibited a significant shared environmental effect. A highly heritable general liability accounts for the parent-child transmission of externalizing psychopathology from parents to their preadolescent offspring. This general liability should be a focus of research for both etiology and intervention.

A Common Genetic Fingerprint in Leprosy and Crohn's Disease?

The cause-and-effect relationship between severe infections and death suggests that microbial pathogens are evolutionary sculptors of the genome. However, the genetic component of susceptibility to infections in the general population is complex and heterogeneous and is modulated by environmental factors such as determinants of microbial virulence. Thus, it is a challenge to identify specific genetic effects in human populations. Availability of the human genome sequence, combined with knowledge of genetic variation, has facilitated the genomewide association study, a powerful approach to detecting genetic associations. In this issue of the Journal, Zhang and colleagues1 describe a genomewide association study of leprosy, . . .

Genetic Effects on Children’s Conversational Language Use

The present study examined the extent of genetic and environmental influences on individual differences in children's conversational language use. Behavioral genetic analyses focused on conversational measures and 2 standardized tests from 380 twins (M = 7.13 years) during the 2nd year of the Western Reserve Reading Project (S. A. Petrill, K. Deater-Deckard, L. A. Thompson, L. S. DeThorne, & C. Schatschneider, 2006) Multivariate analyses using latent factors were conducted to examine the extent of genetic overlap and specificity between conversational and formalized language. Multivariate analyses revealed a heritability of .70 for the conversational language factor and .45 for the formal language factor, with a significant genetic correlation of .37 between the two factors. Specific genetic effects were also significant for the conversational factor. The current study indicated that over half of the variance in children's conversational language skills can be accounted for by genetic effects with no evidence of significant shared environmental influence. This finding casts an alternative lens on past studies that have attributed differences in children's spontaneous language use to differences in environmental language exposure. In addition, multivariate results generally support the context-dependent construction of language knowledge, as suggested by the theory of activity and situated cognition (J. S. Brown, A. Collins, & P. Duguid, 1989; T. A. Ukrainetz, 1998), but also indicate some degree of overlap between language use in conversational and formalized assessment contexts.

The development of fears from early adolesence to young adulthood: a multivariate study

Common fears change over development. Genetic and environmental risk factors for fears are partly shared across fears and partly fear-specific. The nature of the changes in common and fear-specific genetic and environmental risk factors over time is unknown. Self-reported fears were obtained at ages 13-14, 16-17 and 19-20 from 2404 twins in the Swedish Twin Study of Child and Adolescent Development. A multivariate longitudinal twin analysis was conducted with Mx. Eighteen individual items formed four fear factors: animal, blood-injury, situational, and social. The best-fit model had no quantitative or qualitative sex effects or shared environmental effects, but included a strong common factor with a stable cross-time structure with highest loadings on situational and lowest loadings on social fears. New common and fear-specific genetic risk factors emerged over development. With increasing age, genetic effects declined in overall importance and became more fear-specific. Cross-time continuity in specific genetic effects was highest for animal and lowest for social fears. Social fears had a 'burst' of specific genetic effects in late adolescence. Individual-specific environmental factors impacted both on the general fear factor and on specific fears. Compared to genetic effects, the impact of the unique environment was more time-specific. Genetic and environmental risk factors for individual fears are partly mediated through a common fear factor and are partly fear-specific in their effect. The developmental pattern of these risk factors is complex and dynamic with new common and specific genetic effects arising in late adolescence and early adulthood.

Genetics of tension‐type headache: A population based twin study

The purpose was to investigate the importance of genetic and environmental factors in tension-type headache using a genetic modeling analysis. Twins age 12-41 years old from the population based Danish Twin Registry received a validated posted questionnaire about tension-type headache and migraine. Inclusion required that both twins in a pairs replied on the questionnaire and known zygosity. Twin pairs where one or both twins had co-occurrence of migraine were excluded. Migraine significantly increases the risk as well as the frequency of tension-type headache. The quantitative genetic modeling included 2,437 monozygotic (MZ), 2,720 same gender dizygotic (DZ), and 2,203 opposite gender DZ twin pairs without co-occurrence of migraine. Polychoric correlations were significantly higher in MZ than same gender DZ twin pairs analyzed separately by gender, while polychoric correlation were higher in same gender than opposite gender DZ twin pairs, although this was not significant in the comparison with male same gender DZ twin pairs. The best fitting model is based on gender specific prevalence and variance components without gender specific genetic effects. Heritability estimates of 48% in men and 44% in women were obtained. Genetic effects contribute to nearly half of variance in the liability to tension-type headache.

Covariance of Isometric and Dynamic Arm Contractions: Multivariate Genetic Analysis

The purpose of the present study was to examine genetic and environmental contributions to individual differences in maximal isometric, concentric and eccentric muscle strength and muscle cross-sectional area (MCSA) of the elbow flexors. A generality versus specificity hypothesis was explored to test whether the 4 strength variables share a genetic component or common factors in the environment or whether the genetic/environmental factors are specific for each strength variable. The 4 variables under study were measured in 25 monozygotic and 16 dizygotic male Caucasian twin pairs (22.4 +/- 3.7 years). The multivariate genetic analyses showed that all 4 variables shared a genetic and environmental component, which accounted for 43% and 6% in MCSA (h2 = 81%), 47% and 20% in eccentric (h2 = 65%), 58% and 4% in isometric (h2 = 70%) and 32% and 1% in concentric strength (h2 = 32%) respectively. The remaining variation was accounted for by contraction type specific and muscle cross-sectional area specific genetic and environmental effects, which accounted for 38% and 14% in MCSA, 18% and 15% in eccentric, 12% and 26% in isometric and 0% and 67% in concentric strength respectively. This exploratory multivariate study suggests shared pleiotropic gene action for MCSA, eccentric, isometric and concentric strength, with a moderate to high genetic contribution to the variability of these characteristics.

New Evidence on Variations of Human Body Burden of Methylmercury from Fish Consumption

Epidemiologic studies commonly use mercury (Hg) level in hair as a valid proxy to estimate human exposure to methylmercury (MeHg) through fish consumption. This study presents the results yielded by a complete data set on fish consumption habits, Hg levels in edible fish resources, and corresponding Hg accumulation in hair, gathered in three distinct communities of eastern Canada. For one of these communities, the average hair Hg concentration was 14 times less than the expected value based on calculated daily oral exposure and current knowledge of MeHg metabolism. This finding could be explained by differences in specific genetic characteristics and/or interactive effects of other dietary components.