Relative Contribution Of Genetic Factors Research Articles

Association of Typhoid Fever Severity with Polymorphisms at Nucleotide Oligomerization Binding Domain 2 (NOD2) and Natural Resistance Associated Macrophage Protein 1 (NRAMP1) Genes in A Sample of Iraqi Patients

Background and aim: Typhoid fever is one of the major health problems facing humanity of all ages. This study was conducted to investigate the relative contribution of genetic factors to the severity of typhoid fever in a sample of the Iraqi population. Materials and Methods: Blood samples were collected from 52 patients suffering from typhoid fever that was previously diagnosed using conventional and genetic methods at Ibn Al-Baladi Hospital in Baghdad and 52 apparently healthy volunteers as a control group. DNA was extracted from peripheral blood and genotyped for NRAMP1 Intron 4 (469+14 G/C) / rs3731865 and NOD2 Exon 8 (2722 G/C) / rs2066845 single nucleotide polymorphism (SNP) using the Nested T-ARMS PCR method. Results: explained that patients with at least one copy of the NOD2 (C) allele, whether (homozygote or heterozygote) had a high risk of severity of Typhoid fever with highly significant (P≤0.01), as well as results found that there was no association between the occurrence of NRAMP1 rs3731865 Intron 4 (469+14 G/C) with severity of Typhoid fever. Conclusion: The incidence of NOD2 Exon 8 (2722 G/C) rs2066845 SNP plus the C allele could be related to the severity of Typhoid fever in this particular Iraqi population.

Dietary Oncopharmacognosy as a Crosswalk between Precision Oncology and Precision Nutrition

While diet and nutrition are modifiable risk factors for many chronic and infectious diseases, their role in cancer prevention and control remains under investigation. The lack of clarity of some diet–cancer relationships reflects the ongoing debate about the relative contribution of genetic factors, environmental exposures, and replicative errors in stem cell division as determinate drivers of cancer risk. In addition, dietary guidance has often been based upon research assuming that the effects of diet and nutrition on carcinogenesis would be uniform across populations and for various tumor types arising in a specific organ, i.e., that one size fits all. Herein, we present a paradigm for investigating precision dietary patterns that leverages the approaches that led to successful small-molecule inhibitors in cancer treatment, namely understanding the pharmacokinetics and pharmacodynamics of small molecules for targeting carcinogenic mechanisms. We challenge the scientific community to refine the paradigm presented and to conduct proof-in-concept experiments that integrate existing knowledge (drug development, natural products, and the food metabolome) with developments in artificial intelligence to design and then test dietary patterns predicted to elicit drug-like effects on target tissues for cancer prevention and control. We refer to this precision approach as dietary oncopharmacognosy and envision it as the crosswalk between the currently defined fields of precision oncology and precision nutrition with the goal of reducing cancer deaths.

Maternal depressive symptoms and children's cognitive school readiness: the role of gene-environment interplay.

Maternal depressive symptoms are a robust risk factor for poor cognitive outcomes in children, yet the role of gene-environment interplay in this association is not well understood. The objective of this study was to evaluate gene-environment interaction in the association between maternal depressive symptoms and children's cognitive school readiness. Data come from a population-based birth cohort of 538 twin pairs. Maternal depressive symptoms were self-reported (Centre for Epidemiologic Studies Depression Scale) when children were aged 6 and 18 months (a mean score was used). Children's cognitive school readiness was assessed using the Lollipop Test when children were aged 5 years. Analyses were conducted with structural equation modeling. Maternal depressive symptoms were correlated with children's cognitive school readiness (r = -0.10). Shared environmental factors explained most of the variance in children's cognitive school readiness (52%). The remaining variance was accounted for by genetic (30%) and nonshared environmental factors (18%). As the level of maternal depressive symptoms increased, the relative contribution of nonshared environmental factors to the variance in children's cognitive school readiness increased (0.14 [95% CI: 0.04 to 0.24]), whereas the relative contribution of genetic factors decreased (-0.28 [-0.64 to 0.08]). In contexts of elevated maternal depressive symptoms, environmental - and potentially modifiable - factors may be especially important for shaping children's cognitive outcomes. This suggests that interventions to improve the early childhood environment of children exposed to maternal depressive symptoms may improve their cognitive outcomes.

Nature and Nurture: Brain Region-Specific Inheritance of Sleep Neurophysiology in Adolescence.

Sleep-specific oscillations of spindles and slow waves are generated through thalamocortical and corticocortical loops, respectively, and provide a unique opportunity to measure the integrity of these neuronal systems. Understanding the relative contribution of genetic factors to sleep oscillations is important for determining whether they constitute useful endophenotypes that mark vulnerability to psychiatric illness. Using high-density sleep EEG recordings in human adolescent twin pairs (n = 60; 28 females), we find that over posterior regions 80-90% of the variance in slow oscillations, slow wave, and spindle activity is due to genes. Surprisingly, slow (10-12 Hz) and fast (12-16 Hz) anterior spindle amplitude and σ power are largely driven by environmental factors shared among the twins. To our knowledge this is the first example of a neural phenotype that exhibits a strong influence of nature in one brain region, and nurture in another. Overall, our findings highlight the utility of the sleep EEG as a reliable and easy to measure endophenotype during adolescence. This measure may be used to measure disease risk in development before the onset of a psychiatric disorder; the location within the brain of deficits in sleep neurophysiology may suggest whether the ultimate cause is genetic or environmental.SIGNIFICANCE STATEMENT Two cardinal oscillations of sleep, slow waves and sleep spindles, play an important role in the core functions of sleep including memory consolidation, synaptic plasticity, and the recuperative function of sleep. In this study, we use a behavioral genetics approach to examine the heritability of sleep neurophysiology using high-density EEG in a sample of early adolescent twins. Our findings reveal a strong influence of both environmental and genetic factors in shaping these oscillations, dependent on brain region. Thus, during a developmental period when brain structure and function is in flux, we find that the sleep EEG is among the most heritable of human traits over circumscribed brain regions.

Heritability of siesta and night-time sleep as continuously assessed by a circadian-related integrated measure

Siesta is a relevant aspect of sleep due to its posited relationship with health or cognitive function. However, unlike night-time sleep, studies about daytime-sleep determinants and characteristics are scarce, and the genetic/environmental structure of siesta is still unknown. Our aim was to explore the relative contribution of genetic and environmental factors to variation in sleep-wake rhythm, measured by a continuous assessment of temperature-activity-position (TAP), which allows for diurnal sleep analysis. The sample comprised 53 pairs of female twins (28 MZ and 25 DZ), selected from the Murcia Twin Register. Mean age of participants was 52 (SD: 6.03). Zygosity was determined by DNA. We conducted separate univariate analyses to study the sources of variance of daytime and night-time sleep parameters. About 60% of the sample reported to take siesta at least once a week. Heritability of taking siesta and daytime sleep duration was 65 and 61% respectively. Other sleep parameters obtained by TAP showed heritability estimates between 36 and 69%, suggesting a relevant impact of genetic factors on sleep rhythm. This is the first study to investigate the relative contribution of genetic factors to siesta. By using TAP, we introduce a novel approach to the study of diurnal sleep characteristics.

Childhood Trauma and Two Stages of Alcohol Use in African American and European American Women: Findings from a Female Twin Sample.

The current investigation assessed for moderating effects of childhood trauma on genetic and environmental contributions to timing of alcohol use initiation and alcohol use disorder in African American (AA) and European American (EA) women. Data were drawn from diagnostic telephone interviews conducted with 3786 participants (14.6% AA) in a longitudinal female twin study. Childhood trauma was defined alternately as child maltreatment and more broadly to include other events (e.g., witnessing violence). Phenotypic associations between childhood trauma and alcohol outcomes were estimated using logistic regression analyses. Twin modeling was conducted to test for moderating effects of childhood trauma on the contributions of genetic and environmental factors to timing of initiation and alcohol use disorder. Under both definitions, childhood trauma was associated with early initiation (relative risk ratios: 1.90, 1.72) and alcohol use disorder (odds ratios: 1.92, 1.76). Yet gene by environment effects were observed only for child maltreatment and timing of initiation in EA women, with heritable influences less prominent in those who had experienced child maltreatment (0.35, 95% CI: 0.05-0.66 vs. 0.52, 95% CI: 0.30-0.73). We found more similarities than differences in the association of childhood trauma with alcohol outcomes across racial/ethnic groups, trauma type, and stages of alcohol use. However, findings suggest that the relative contribution of genetic factors to alcohol outcomes differs by childhood maltreatment history in EA women specifically in the earliest stage of alcohol use.

Phenotypic and familial associations between childhood maltreatment and cannabis initiation and problems in young adult European-American and African-American women

BackgroundChildhood maltreatment is a known risk factor for cannabis initiation and problem use, but the extent to which this association is attributable to shared familial influences is unknown. We estimate the magnitude of associations between childhood maltreatment, timing of cannabis initiation, and cannabis-related problems, in European-American (EA) and African-American (AA) women, and parse the relative influence of additive genetic (A), shared environmental (C), and individual-specific environmental (E) factors on these constructs and their covariation. MethodsData were from diagnostic telephone interviews conducted with 3786 participants (14.6% AA) in a population-based study of female twins. Logistic regression analyses and twin modeling were used to test for associations, and estimate the relative contributions of genetic and environmental influences to childhood maltreatment and cannabis outcomes and their covariation. ResultsMaltreatment was significantly associated with increased likelihood of cannabis initiation before age 15 among EAs (OR=6.33) and AAs (OR=3.93), but with increased likelihood of later initiation among EAs only (OR=1.68). Maltreatment was associated with cannabis problems among both groups (EA OR=2.32; AA OR=2.03). Among EA women, the covariation between maltreatment and cannabis outcomes was primarily attributable to familial environment (rC=0.67–0.70); among AAs, only individual-specific environment contributed (rE=0.37–0.40). ConclusionChildhood maltreatment is a major contributor to early initiation of cannabis as well as progression to cannabis problems in both AA and EA women. Distinctions by race/ethnicity are not in the relative contribution of genetic factors, but rather in the type of environmental influences that contribute to stages of cannabis involvement.

Search for risk genes in schizophrenia

Schizophrenia is asevere psychiatric disease affecting approximately 0.5-1% of the general population. The relative contribution of genetic factors has been estimated to be 64-81%. This review summarizes recent efforts to identify genetic variants associated with schizophrenia. Relevant linkage and candidate genes as well as genome wide association studies, studies on copy number variants and next generation sequencing are presented and discussed. The latest and worldwide largest study on the genetics of schizophrenia found 128 genome wide significant single nucleotide polymorphisms (SNP) and 108 genome wide loci. The most obvious association is with genetic variations in the major histocompatibility complex (MHC). Besides polymorphisms, structural variants in the form of copy number variants (CNV), such as microdeletions and microduplications have a very high impact in asubgroup of patients. These CNVs are mainly microdeletions on 1q21.1, 2p16.3, 3q29, 15q13.3 and 16p11.2 as well as alarge deletion on 22q11.21 and amicroduplication on 16p11.2. Alarge new body of evidence on the genetics of schizophrenia is expected through next generation sequencing approaches. Future studies will particularly address the functional characterization of genetic variants.

Heritability of the shape of subcortical brain structures in the general population.

The volumes of subcortical brain structures are highly heritable, but genetic underpinnings of their shape remain relatively obscure. Here we determine the relative contribution of genetic factors to individual variation in the shape of seven bilateral subcortical structures: the nucleus accumbens, amygdala, caudate, hippocampus, pallidum, putamen and thalamus. In 3,686 unrelated individuals aged between 45 and 98 years, brain magnetic resonance imaging and genotyping was performed. The maximal heritability of shape varies from 32.7 to 53.3% across the subcortical structures. Genetic contributions to shape extend beyond influences on intracranial volume and the gross volume of the respective structure. The regional variance in heritability was related to the reliability of the measurements, but could not be accounted for by technical factors only. These findings could be replicated in an independent sample of 1,040 twins. Differences in genetic contributions within a single region reveal the value of refined brain maps to appreciate the genetic complexity of brain structures.

Hereditary and environmental factors causing total joint replacement due to hip and knee osteoarthritis – a twin registry based prospective cohort study

The relative contribution of genetic factors and more modifiable environmental factors to a clinicallyrelevant osteoarthritis (OA) diagnosis is unkown. In this paper we present an ongoing study on the geneticcontribution to total joint replacement (TJR) due to hip and knee OA and effects of lifestyle and lifestylerelated conditions on TJR due to OA. We have linked data on incident OA from the Norwegian ArthroplastyRegistry were l with the Norwegian Twin Registry on the National ID number in 2014, thus obtaining apopulation based cohort of same-sex twins born 1915-60. Data on height, weight and lifestyle were selfreportededin questionnaires conducted between 1978 and 1992. The monozygotic (MZ) and dizygotic(DZ) concordances as well as the genetic contribution vs. contribution of more modifiable, environmentalfactors to arthroplasty will be examined in separate analyses for the hip and the knee joint. The samplecomprised N=18058 twins (N=3803 MZ and N=5226 DZ pairs) including N=9650 (53.4%) females and amean (SD) age of 38 (12.3) years at questionnaire response. Some preliminary analyses have been performedshowing a higher concordance for TJR due to hip OA among MZ (0.36) than DZ twins (0.16), which maybe consistent with a genetic contribution to hip OA. TJR due to hip OA may be determined by geneticfactors. Results for the knee joint as well as final results from hereditary analyses and co-twin controlanalyses of will be published consecutively from 2016.

Social inequalities in reception of social welfare support: A population based twin study

Social welfare support runs in families. Recent studies using Nordic registry data have found individualdifferences in genetic factors to be of substantial importance for medical benefits. However, to date there hasbeen no genetically informative studies on receiving social welfare support. To prevent young adults to notdrop out of the work life and become recipients of social welfare support, it is of substantial interest toclarify to what extent the familiarity of social welfare support is due to genetic or social differences betweenfamilies. We used data from the Historical-Event Database on 7,698 Norwegian twins born 1967-1979 toestimate the relative contribution of genetic factors, the effective familial environment (i.e. the “sharedenvironment”), and individual-specific environmental factors. We found that the two forms of familial risk,genetic and shared environmental, explained 39% and 45%, respectively, of the risk for receiving socialwelfare support among young Norwegian twins. Only 17% of the variance in risk factors could be explainedby individual-specific risk factors. It appears that risk for receiving social welfare support can to a greatextent be explained by environmental differences between families. Therefore prevention strategies targetingsocial inequalities between families would indeed be effective. Furthermore, genetic risk factors are alsoimportant in explaining risk for receiving social welfare support. These effects could be mediated throughheritable traits related to substance abuse, psychiatric disorders, and personality. Individual-specific risk factorswere of very little importance. Hence, with regard to receiving social welfare support, family matters.

Twin-sibling study and meta-analysis on the heritability of maximal oxygen consumption.

Large individual differences exist in aerobic fitness in childhood and adolescence, but the relative contribution of genetic factors to this variation remains to be established. In a sample of adolescent twins and siblings (n = 479), heart rate (HR) and maximal oxygen uptake (V̇o2max) were recorded during the climax of a graded maximal exercise test. In addition, V̇o2max was predicted in two graded submaximal exercise tests on the cycle ergometer and the treadmill, using extrapolation of the HR/V̇o2 curve to the predicted HRmax. Heritability estimates for measured V̇o2max were 60% in ml/min and 55% for V̇o2max in ml·min(-1)·kg(-1). Phenotypic correlations between measured V̇o2max and predicted V̇o2max from either submaximal treadmill or cycle ergometer tests were modest (0.57 < r < 0.70), in part because of the poor agreement between predicted and actual HRmax. The majority of this correlation was explained by genetic factors; therefore, the submaximal exercise tests still led to very comparable estimates of heritability of V̇o2max. To arrive at a robust estimate for the heritability of V̇o2max in children to young adults, a sample size weighted meta-analysis was performed on all extant twin and sibling studies in this age range. Eight studies, including the current study, were meta-analyzed and resulted in a weighted heritability estimate of 59% (ml/min) and 72% (ml·min(-1)·kg(-1)) for V̇o2max. Taken together, the twin-sibling study and meta-analyses showed that from childhood to early adulthood genetic factors determine more than half of the individual differences in V̇o2max.

White Matter Lesion Progression: Genome-Wide Search for Genetic Influences.

White matter lesion (WML) progression on magnetic resonance imaging is related to cognitive decline and stroke, but its determinants besides baseline WML burden are largely unknown. Here, we estimated heritability of WML progression, and sought common genetic variants associated with WML progression in elderly participants from the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) consortium. Heritability of WML progression was calculated in the Framingham Heart Study. The genome-wide association study included 7773 elderly participants from 10 cohorts. To assess the relative contribution of genetic factors to progression of WML, we compared in 7 cohorts risk models including demographics, vascular risk factors plus single-nucleotide polymorphisms that have been shown to be associated cross-sectionally with WML in the current and previous association studies. A total of 1085 subjects showed WML progression. The heritability estimate for WML progression was low at 6.5%, and no single-nucleotide polymorphisms achieved genome-wide significance (P<5×10(-8)). Four loci were suggestive (P<1×10(-5)) of an association with WML progression: 10q24.32 (rs10883817, P=1.46×10(-6)); 12q13.13 (rs4761974, P=8.71×10(-7)); 20p12.1 (rs6135309, P=3.69×10(-6)); and 4p15.31 (rs7664442, P=2.26×10(-6)). Variants that have been previously related to WML explained only 0.8% to 11.7% more of the variance in WML progression than age, vascular risk factors, and baseline WML burden. Common genetic factors contribute little to the progression of age-related WML in middle-aged and older adults. Future research on determinants of WML progression should focus more on environmental, lifestyle, or host-related biological factors.

The heritability of prostate cancer in the Nordic Twin Study of Cancer.

Prostate cancer is thought to be the most heritable cancer, although little is known about how this genetic contribution varies across age. To address this question, we undertook the world's largest prospective study in the Nordic Twin Study of Cancer cohort, including 18,680 monozygotic (MZ) and 30,054 dizygotic (DZ) same-sex male twin pairs. We incorporated time-to-event analyses to estimate the risk concordance and heritability while accounting for censoring and competing risks of death, essential sources of biases that have not been accounted for in previous twin studies modeling cancer risk and liability. The cumulative risk of prostate cancer was similar to that of the background population. The cumulative risk for twins whose co-twin was diagnosed with prostate cancer was greater for MZ than for DZ twins across all ages. Among concordantly affected pairs, the time between diagnoses was significantly shorter for MZ than DZ pairs (median, 3.8 versus 6.5 years, respectively). Genetic differences contributed substantially to variation in both the risk and the liability [heritability = 58% (95% confidence interval, 52%-63%)] of developing prostate cancer. The relative contribution of genetic factors was constant across age through late life with substantial genetic heterogeneity even when diagnosis and screening procedures vary. Results from the population-based twin cohort indicate a greater genetic contribution to the risk of developing prostate cancer when addressing sources of bias. The role of genetic factors is consistently high across age. Findings affect the search for genetic and epigenetic markers and frame prevention efforts.

P38 ‐ Nut allergy and patterns of specific IgE components in two identical twins

Peanut allergy currently affects 1-2% of children in the developed countries. The role of genetics in its aetiology is unknown. For complex genetic traits, twin studies provide information on the relative contribution of genetic factors, as they decrease the relative confounding effects of the environmenl. The significantly higher concordance rate of peanut allergy among monozygotes suggests strongly that there is a significant genetic influence. On the other hand component-resolved diagnostics (CRD) utilize purified native or recombinant allergens to detect IgE sensitivity to individual allergen molecules and have gained growing importance. CRD allows to some extent discrimination between clinically significant and irrelevant specific IgE results and establishing of sensitisation patterns with particular prognostic outcomes. Here is a case of identical male twins where the pattern of results, including that of distribution of IgE specific antibodies to individual molecules, is also identical. In the age of 4 yrs one had an ice cream with nut sprinkle and instantly developed lip swelling. They were both tested for nut and egg, as they had never had either before, were positive to both and avoided them ever since, although the other twin had once cooked egg accidentally and within few minutes developed abdominal pain and diarrhoea. They both have IgE antibodies to House Dust Mite, egg white and early and late tree pollens. Hazelnut is the predominant nut, followed by peanut and almond and all the rest negative. In Skin Prick Testing the strongest response was to peanut with moderate responses to almond and hazelnut and the rest negative. Analysis of the IgE antibody levels against individual nut components showed a predominance of Ara8, followed by Ara2 with Ara1 and Ara8 negative. The results arranged in a graph form two lines of identical shape. As far as we are concerned there is no similar report on identical twins and it would be useful to the geneticists as to what makes the same allergy not only manifested in both twins but also involving the same peanut molecules out of the 18 identified as being capable of binding allergen-specific IgE antibodies.

Maternal vitamin D predominates over genetic factors in determining neonatal circulating vitamin D concentrations

There are multiple potential regulators of neonatal vitamin D status of environmental, genetic, and epigenetic origins. The relation between these factors and circulating neonatal vitamin D has yet to be fully characterized. The aim of this study was to examine the relative contribution of genetic factors, maternal circulating 25-hydroxyvitamin D [25(OH)D] concentrations, and the placental methylation level of the gene that encodes the primary catabolic enzyme of active vitamin D [25(OH)D-24-hydroxylase encoded by CYP24A1] to neonatal 25(OH)D concentrations. We used the classical twin study design to determine the genetic contribution to neonatal 25(OH)D. A total of 86 twin pairs (32 monozygotic and 54 dizygotic twin pairs) were included in this study. Serum 25(OH)D was measured by using a 25(OH)D kit. CYP24A1 promoter DNA methylation was measured by means of matrix-assisted laser desorption time-of-flight mass spectrometry. Maternal and neonatal 25(OH)D showed a strong association (R² = 0.19). Monozygotic and dizygotic within-pair serum 25(OH)D correlations were similar (R² = 0.71 and 0.67, respectively), which suggested no genetic effect. Placental CYP24A1 methylation did not show an association with maternal or neonatal 25(OH)D concentrations. Our results suggest that maternal circulating 25(OH)D is the most significant regulator of neonatal circulating 25(OH)D concentrations, with underlying genetic factors playing a limited role. The placental methylation of the CYP24A1 promoter appears subject to a genetic influence, although no evidence of a relation between the methylation level of this gene and circulating maternal or neonatal 25(OH)D was apparent.

Proteinuria and Glomerular Damage in Rab3A Knockout Mice Chronically Fed a High-Glucose Diet

Background/Aims: The relative contribution of genetic factors and dietary patterns to glomerular damage in healthy individuals and prediabetic conditions is currently unclear. All Rab3A knockout (KO) mice spontaneously develop macroalbuminuria, but only male mice exhibit a glucose-intolerant phenotype, thus making the model suitable to examine the impact of a diet on preexisting podocyte damage. Methods: Male and female Rab3A KO and wild-type (WT) mice were chronically fed a high-glucose diet (HGD). Biochemical tests, histology and immunohistochemistry were periodically performed whilst primary podocytes served for in vitro analyses. Results: Chronic administration of an HGD did not induce de novo alterations in WT kidneys but caused progressive worsening of podocyte and glomerular damage in both male and female Rab3A KO. Though glomerular lesions, reminiscent of human diabetic nephropathy, were more severe in male mice, overt proteinuria and renal damage were also evident in female mice. The in vitro analysis of Rab3A WT and KO podocytes revealed diminished actin plasticity in the cell processes of KO podocytes. Furthermore, a modest increase in glucose concentration induced profound cytoskeletal changes only in Rab3A KO cells. Conclusions: Our data show that chronic administration of an HGD to Rab3A KO mice that have a genetic defect that impairs podocyte actin plasticity results in increased podocyte damage and leads to overt proteinuria. If the same diet is given to male Rab3A KO animals, with additionally altered glucose homeostasis, this results in renal lesions similar to those of human diabetic nephropathy.

The Shared Genetics of Migraine and Anxious Depression

To investigate (1) whether shared genetic factors influence migraine and anxious depression; (2) whether the genetic architecture of migraine depends on anxious depression; (3) whether the association between migraine and anxious depression is causal. Migraine and anxious depression frequently occur together, but little is known about the mechanisms causing this association. A twin study was conducted to model the genetic architecture of migraine and anxious depression and the covariance between them. Anxious depression was also added to the model as a moderator variable to examine whether anxious depression affects the genetic architecture of migraine. Causal models were explored with the co-twin control method. Modest but significant phenotypic (rP=0.28), genetic (rG=0.30), and nonshared environmental (rE=0.26) correlations were found between the 2 traits. Interestingly, the heritability of migraine depended on the level of anxious depression: the higher the anxious depression score, the lower the relative contribution of genetic factors to the individual differences in migraine susceptibility. The observed risk patterns in discordant twins are most consistent with a bidirectional causal relationship. These findings confirm the genetic association between migraine and anxious depression and are consistent with a syndromic association between the 2 traits. This highlights the importance of taking comorbidity into account in genetic studies of migraine, especially in the context of selection for large-scale genotyping efforts. Genetic studies may be most effective when migraine with and without comorbid anxious depression are treated as separate phenotypes.

Genetic-environmental interactions in asthma and allergy: a study in a closed population exposed to different environments

Asthma and allergy are common chronic diseases caused by genetic and environmental factors. To study the effect of different environments on the prevalence of both diseases in an isolated founder population that resettled in different geographic and environmental areas (namely, the genetically homogeneous population that immigrated to Israel from Cochin, India, 50 years ago). Respiratory and allergy symptoms were recorded by a questionnaire. The relative contribution of genetic factors on asthma and allergy was established by comparing Cochin with non-Cochin Jews living in the Jerusalem mountains; the relative contribution of the environment was determined by comparing mountain Cochin Jews with those living in the desert. The study was conducted from January to October 2004. A total of 983 individuals (481 mountain Cochins, 353 desert Cochins, and 149 non-Cochins) were studied. The overall prevalence of asthma in Cochins was 23.7%; and of allergy, 29.5%. The rate of asthma and/or allergy in Cochins in the mountains was significantly higher than in control non-Cochins. The rates of both asthma and allergy among Cochin Jews in the mountains were significantly higher than those among Cochin Jews in the desert, the former because of a higher prevalence of allergic asthma. The rates of nonallergic asthma and allergy without asthma were similar in both environments. Two different asthma and allergy phenotypes were detected that share a distinct genetic background but differ in the environmental influences. Allergic asthma is strongly determined by both genetic and environmental factors, whereas nonallergic asthma or atopy without asthma is determined mainly by genetic factors and is less influenced by environmental factors.

Inheritance of Occlusal Topography: A Twin Study

This was to determine the relative contribution of genetic factors on the morphology of occlusal surfaces of mandibular primary first molars by employing the twin study model. The occlusal morphology of mandibular primary first molar teeth from dental casts of 9 monozygotic (MZ) twin pairs and 12 dizygotic (DZ) twin pairs 4 to 7 years old, were digitized by contact-type three-dimensional (3D) scanner. To compare the similarity of occlusal morphology between twin sets, each twin pair of occlusal surfaces was superimposed to establish the best fit by using computerized least squared techniques. Heritability was computed using a variance component model, adjusted for age and gender. DZ pairs demonstrated a greater degree of occlusal morphology variance. The total amount of difference in surface overlap was 0.0508 mm (0.0018 (inches) for the MZ (n=18) sample and 0.095 mm (0.0034 inches) for the DZ (n=24) sample and were not statistically significant (p=0.2203). The transformed mean differences were not statistically significantly different (p=0.2203). Heritability estimates of occlusal surface areas for right and left mandibular primary first molars were 97.5% and 98.2% (p<0.0001), respectively. Occlusal morphology of DZ twin pairs was more variable than that of MZ twin pairs. Heritability estimates revealed that genetic factors strongly influence occlusal morphology of mandibular primary first molars.