Discordant Monozygotic Twin Pairs Research Articles

Regional gray matter reductions are associated with genetic liability for anxiety and depression: An MRI twin study

BackgroundThe influence of genetic and/or environmental factors on the volumetric brain changes observed in subjects affected by anxiety and depression disorders remains unclear. The current study aimed to investigate whether genetic and environmental liabilities make different contributions to abnormalities in gray matter volume (GMV) in anxiety and depression using a concordant and discordant MZ twin pairs design. MethodsFifty-three magnetic resonance imaging (3T) brain scans were obtained from monozygotic (MZ) twins concordant (6 pairs) and discordant (10 pairs) for lifetime anxiety and depression disorders and from healthy twins (21 subjects). We applied voxel-based morphometry to analyse GMV differences. Concordant affected twins were compared to healthy twins and within-pairs comparisons were performed in the discordant group. ResultsGMV reductions in bilateral fusiform gyrus and amygdala were observed in concordant affected twins for anxiety and depression compared to healthy twins. No intrapair differences were found in GMV between discordant affected twins and their healthy co-twins. LimitationsThe sample size was modest. This might explain why no intrapair differences were found in the discordant MZ twin group. ConclusionsAs concordant affected MZ twins are believed to have a particularly high genetic liability for the disorder, our findings suggest that fusiform gyrus and amygdala gray matter reductions are related to a genetic risk for anxiety and depression. Discrepancies in regard to brain abnormalities in anxiety and depression may be related to the admixture of patients with GMV abnormalities mainly accounted for by genetic factors with patients presenting GMV mainly accounted for by environmental factors.

Regulation of the Pituitary-Thyroid Axis in Adulthood Is Not Related to Birth Weight: Evidence from Extremely Birth Weight–Discordant Monozygotic Danish Twin Pairs

Low birth weight has been linked with changes in thyroid function in adulthood, but it is unknown whether fetal programming or underlying genetic and environmental factors explains the association. We hypothesized that birth weight influences the pituitary-thyroid set point in adults. A total of 152 birth weight-discordant monozygotic twin pairs with a median age of 57 years (interquartile range: 33-63) were ascertained from the Danish Twin Registry in 2010. Serum thyroid-stimulating hormone (TSH), free thyroxine (FT4), and triiodothyronine (T3) levels were measured. Birth weights were retrieved from midwife records (individuals born before 1973) and the Danish Birth Record Registry (all other participants) Birth weight was inversely associated with serum levels of FT4 (β=-0.48 pmol/[L·kg], p=0.014) and serum T3 (β=-0.09 nmol/[L·kg], p=0.010), but not serum TSH after adjustment for age, sex, and current use of tobacco products, when the twins were investigated as singletons. Serum levels of TSH and T3 were similar in within twin-pair analyses, while serum FT4 was higher in twins with the lowest birth weight (median difference 0.3 mIU/L). When the analyses were repeated in twin pairs (n=46 pairs) characterized by extreme difference in birth weight (>0.5 kg), serum TSH, T3, and FT4 levels were similar in twins with high and low birth weight. The proportion of individuals with serum TSH level >4 mIU/L or <0.3 mIU/L was identical in both groups. No overall evidence of an association between birth weight and adult pituitary-thyroid axis set point, after control for genetic and environmental factors, could be demonstrated.

Regulation of the Pituitary-Thyroid Axis in Adulthood is Not Related to Birth Weight. Evidence From Extremely Birth Weight Discordant Monozygotic Danish Twin Pairs

Regulation of the Pituitary-Thyroid Axis in Adulthood is Not Related to Birth Weight. Evidence From Extremely Birth Weight Discordant Monozygotic Danish Twin Pairs

FMRI and corpus callosum relationships in monozygotic twins discordant for handedness

To further investigate brain structure and function in 26 handedness discordant monozygotic twin pairs (MzHd), MRI and behavioural assessments were carried out. These showed significant correlation between language-specific functional laterality in inferior and middle frontal gyri, and anterior corpus callosum. Previous studies of handedness discordant monozygotic twins failed to resolve the issue concerning handedness and hemispheric laterality for language due to methodological disparities. The results would be relevant to genetic theories as well as to brain structure:function explanations. MzHd twins underwent MRI and fMRI scanning as well as behavioural assessment of motor performance and cognition. There were significant differences on MRI and fMRI laterality measures, as well as a significant correlation between anterior callosal widths and functional laterality. LH twins showed higher frequencies of atypical functional laterality. There was no significant within-twin pair correlation on fMRI verbal laterality, nor did results show within-twin pair differences on verbal fluency or IQ. Implications for the field of laterality research pertain to frontal hemispheric equipotentiality for verbal processes in healthy individuals. In particular, there can be an apparent lack of cognitive 'cost' to atypical laterality. An fMRI verbal laterality index correlated significantly with corpus callosum widths near Broca's area.

De novo and inherited CNVs in MZ twin pairs selected for discordance and concordance on Attention Problems

Copy number variations (CNVs) have been reported to be causal suspects in a variety of psychopathologic traits. We investigate whether de novo and/or inherited CNVs contribute to the risk for Attention Problems (APs) in children. Based on longitudinal phenotyping, 50 concordant and discordant monozygotic (MZ) twin pairs were selected from a sample of ∼3200 MZ pairs. Two types of de novo CNVs were investigated: (1) CNVs shared by both MZ twins, but not inherited (pre-twinning de novo CNVs), which were detected by comparing copy number (CN) calls between parents and twins and (2) CNVs not shared by co-twins (post-twinning de novo CNVs), which were investigated by comparing the CN calls within MZ pairs. The association between the overall CNV burden and AP was also investigated for CNVs genome-wide, CNVs within genes and CNVs outside of genes. Two de novo CNVs were identified and validated using quantitative PCR: a pre-twinning de novo duplication in a concordant-unaffected twin pair and a post-twinning deletion in the higher scoring twin from a concordant-affected pair. For the overall CNV burden analyses, affected individuals had significantly larger CNVs that overlapped with genes than unaffected individuals (P=0.008). This study suggests that the presence of larger CNVs may increase the risk for AP, because they are more likely to affect genes, and confirms that MZ twins are not always genetically identical.

Genome-wide peripheral blood leukocyte DNA methylation microarrays identified a single association with inflammatory bowel diseases

Crohn's disease (CD) and ulcerative colitis (UC) are common forms of inflammatory bowel disease (IBD). Monozygotic (MZ) twin discordance rates and epidemiologic data implicate that environmental changes and epigenetic factors may play a pathogenic role in IBD. DNA methylation (the methylation of cytosines within CpG dinucleotides) is an epigenetic modification, which can respond to environmental influences. We investigated whether DNA methylation might be connected with IBD in peripheral blood leukocyte (PBL) DNA by utilizing genome-wide microarrays. Two different high-throughput microarray-based methods for genome-wide DNA methylation analysis were employed. First, DNA isolated from MZ twin pairs concordant (CD: 4; UC: 3) and discordant (CD: 4; UC: 7) for IBD was interrogated by a custom-made methylation-specific amplification microarray (MSAM). Second, the recently developed Illumina Infinium HumanMethylation450 BeadChip arrays were used on 48 samples of PBL DNA from discordant MZ twin pairs (CD: 3; UC: 3) and treatment-naive pediatric cases of IBD (CD: 14; UC: 8), as well as controls (n = 14). The microarrays were validated with bisulfite pyrosequencing. The MSAMs did not yield significant IBD associations. The Methylation BeadChip approach identified a single DNA methylation association of IBD at TEPP (testis, prostate and placenta-expressed protein) when DNA isolated selectively from peripheral blood mononuclear cells was analyzed (8.6% increase in methylation between CD and control, FDR = 0.0065). Microarray interrogation of IBD-dependent DNA methylation from PBLs appears to have limited ability to detect significant disease associations. More detailed and/or selective approaches may be useful for the elucidation of connections between the DNA methylome and IBD in the future.

P-705 - Copy number variants distribution in a pair of discordant monozygotic twins for the autism spectrum disorder

Introduction Autism is characterized by a broad spectrum of disorders of communication, language skills, social interaction and behaviour (Autism Spectrum Disorder, ASD). Studies of twins’ concordance indicate that 85–90% of the ASD variability can be attributed to a genetic basis with a strong genotype-environment interaction. It has been suggested that copy number variations (CNV) contribute significantly to the phenotypic variability of complex disorders such as autism. 10–15% of monozygotic twin pairs show discordance on ASD. Objectives To evaluate CNVs patterns in a pair of male monozygotic twins discordant for ASD. Aims To identify ASD candidate genomic regions and genes. Methods A pair of discordant monozygotic twins was diagnosed according to ADOS and ADI-R as Autistic Disorder (twin1) and Pervasive Developmental Disorder Not Otherwise Specified (twin2). DNA was obtained from blood and saliva and used to perform a comparative genome hybridization (CGH) analysis with the Agilent 2X400K CGH-array. DNA from each twin was compared with a DNA pool obtained from healthy controls. CGH results were analysed by Agilent Genomic Workbench using ADAM2 algorithm (threshold of 6 and a minimum of 4 probes) to identify CNVs. Results X-fragile and Angelman Syndrome aetiology were discarded. We identified common and private CNV in blood and saliva. Two CNV regions (CNVR) located at 16p11.2 and 1p36.13 were identified as private for twin1 and twin2, respectively. Conclusion CNVR differ among ASD discordant monozygotic twins. 16p11.2 microdeletion syndrome has been related to autism. An in deep characterization could allow us to identify candidate genes in ASD.

Differences in Copy Number Variation between Discordant Monozygotic Twins as a Model for Exploring Chromosomal Mosaicism in Congenital Heart Defects

Studies addressing the role of somatic copy number variation (CNV) in the genesis of congenital heart defects (CHDs) are scarce, as cardiac tissue is difficult to obtain, especially in non-affected individuals. We explored the occurrence of copy number differences in monozygotic (MZ) twins discordant for the presence of a CHD, as an illustrative model for chromosomal mosaicism in CHDs. Array comparative genomic hybridization was performed on peripheral blood-derived DNA obtained from 6 discordant MZ twin pairs and on sex-matched reference samples. To identify CNV differences between both twin members as well as potential CNVs in both twins contributing to the phenotype, DNA from each twin was hybridized against its co-twin, and against a normal control. Three copy number differences in 1 out of 6 MZ twin pairs were detected, confirming the occurrence of somatic CNV events in MZ twins. Further investigation by copy number and (epi)genome sequencing analyses in MZ twins, discordant for the presence of CHDs, is required to improve our knowledge on how postzygotic genetic, environmental and stochastic factors can affect human heart development.

Identification of Type 1 Diabetes–Associated DNA Methylation Variable Positions That Precede Disease Diagnosis

Monozygotic (MZ) twin pair discordance for childhood-onset Type 1 Diabetes (T1D) is ∼50%, implicating roles for genetic and non-genetic factors in the aetiology of this complex autoimmune disease. Although significant progress has been made in elucidating the genetics of T1D in recent years, the non-genetic component has remained poorly defined. We hypothesized that epigenetic variation could underlie some of the non-genetic component of T1D aetiology and, thus, performed an epigenome-wide association study (EWAS) for this disease. We generated genome-wide DNA methylation profiles of purified CD14+ monocytes (an immune effector cell type relevant to T1D pathogenesis) from 15 T1D–discordant MZ twin pairs. This identified 132 different CpG sites at which the direction of the intra-MZ pair DNA methylation difference significantly correlated with the diabetic state, i.e. T1D–associated methylation variable positions (T1D–MVPs). We confirmed these T1D–MVPs display statistically significant intra-MZ pair DNA methylation differences in the expected direction in an independent set of T1D–discordant MZ pairs (P = 0.035). Then, to establish the temporal origins of the T1D–MVPs, we generated two further genome-wide datasets and established that, when compared with controls, T1D–MVPs are enriched in singletons both before (P = 0.001) and at (P = 0.015) disease diagnosis, and also in singletons positive for diabetes-associated autoantibodies but disease-free even after 12 years follow-up (P = 0.0023). Combined, these results suggest that T1D–MVPs arise very early in the etiological process that leads to overt T1D. Our EWAS of T1D represents an important contribution toward understanding the etiological role of epigenetic variation in type 1 diabetes, and it is also the first systematic analysis of the temporal origins of disease-associated epigenetic variation for any human complex disease.

Epigenetic Discordance at Imprinting Control Regions in Twins

Imprinting control regions are differentially methylated in a parent-of-origin-dependent manner and this methylation state is inherited through the germline. These regions control parent-specific monoallelic expression of their target genes. Genetically identical organisms show considerable variation in their epigenomes owing to environmental and stochastic influences creating fluctuations in phenotype. Monozygotic twin pairs discordant for imprinting disorders due to epigenetic changes at imprinting control regions are an example of phenotypic variation caused by extreme variations of the epigenome. Here, we discuss the within-pair epigenetic discordance at imprinted loci, both in phenotypically concordant and discordant monozygotic twin pairs.

Parental depression and offspring psychopathology: a Children of Twins study

Associations between parental depression and offspring affective and disruptive disorders are well documented. Few genetically informed studies have explored the processes underlying intergenerational associations. A semi-structured interview assessing DSM-III-R psychiatric disorders was administered to twins (n=1296) from the Australian Twin Register (ATR), their spouses (n=1046) and offspring (n=2555). We used the Children of Twins (CoT) design to delineate the extent to which intergenerational associations were consistent with a causal influence or due to genetic confounds. In between-family analyses, parental depression was associated significantly with offspring depression [hazard ratio (HR) 1.52, 95% confidence interval (CI) 1.20-1.93] and conduct disorder (CD; HR 2.27, CI 1.31-3.93). Survival analysis indicated that the intergenerational transmission of depression is consistent with a causal (environmental) inference, with a significant intergenerational association in offspring of discordant monozygotic (MZ) twin pairs (HR 1.39, CI 1.00-1.94). Logistic regression analysis suggested that the parental depression-offspring CD association was due to shared genetic liability in the parents and offspring. No intergenerational association was found when comparing the offspring of discordant MZ twins [odds ratio (OR) 1.41, CI 0.63-3.14], but offspring of discordant dizygotic (DZ) twins differed in their rates of CD (OR 2.53, CI 0.95-6.76). All findings remained after controlling for several measured covariates, including history of depression and CD in the twins' spouses. The mechanisms underlying associations between parental depression and offspring psychopathology seem to differ depending on the outcome. The results are consistent with a causal environmental role of parental depression in offspring depression whereas common genetic factors account for the association of parental depression and offspring CD.

Identical but not the same: The value of discordant monozygotic twins in genetic research

Monozygotic (MZ) twins show remarkable resemblance in many aspects of behavior, health, and disease. Until recently, MZ twins were usually called "genetically identical"; however, evidence for genetic and epigenetic differences within rare MZ twin pairs has accumulated. Here, we summarize the literature on MZ twins discordant for Mendelian inherited disorders and chromosomal abnormalities. A systematic literature search for English articles on discordant MZ twin pairs was performed in Web of Science and PubMed. A total number of 2,016 publications were retrieved and reviewed and 439 reports were retained. Discordant MZ twin pairs are informative in respect to variability of phenotypic expression, pathogenetic mechanisms, epigenetics, and post-zygotic mutagenesis and may serve as a model for research on genetic defects. The analysis of single discordant MZ twin pairs may represent an elegant approach to identify genes in inherited disorders.

The Role of Birth Weight in Myopia – The Genes in Myopia Twin Study

Objective: It was the aim of this study to assess the role of birth weight in the development of myopia using a large cohort of Caucasian monozygotic (MZ) and dizygotic (DZ) twins that took part in the Genes in Myopia (GEM) twin study. Methods: The recruitment of all twins in the GEM twin study was facilitated by the Australian Twin Registry. Each twin underwent a standard questionnaire and a comprehensive ocular examination, which included a dilated objective refraction through autorefraction. Myopia was defined as spherical equivalent equal to or worse than –0.50 diopters. Birth weight was determined through self-report as part of the standard questionnaire. Results: A total of 1,224 twins (690 MZ and 534 DZ twins) aged between 18 and 86 years (mean age 52.36 years) were recruited into the GEM study. The mean birth weight was similar between MZ (2.34 kg) and DZ twins (2.46 kg; p > 0.05). Logistic regression showed no significant association with birth weight and myopia for all twins (p = 0.26), as well as for MZ (p = 0.18) and DZ twins (p = 0.70) separately, with no gender effect (p = 0.23). Moreover, there was no significant difference in mean birth weight between discordant (presence/absence) MZ (myopes = 2.33 kg, non-myopes = 2.39 kg) and DZ twin pairs (myopes = 2.39 kg, non-myopes = 2.43 kg; p = 0.91 and 0.95, respectively). Conclusion: Birth weight appears to have little to no role in the development of myopia. In addition, birth weight was not a predictor of the discordance of myopia in MZ and DZ twin pairs.

Association of the Lipoprotein Lipase Gene T+495G Polymorphism With Central Obesity and Serum Lipids in a Twin Study

The lipoprotein lipase (LPL) gene polymorphism is possibly involved in the pathophysiology of central obesity and dyslipidemia. The aim of this study was to investigate the association of LPL gene T+495G polymorphism with central obesity and serum lipids. A total of 961 adult twin pairs were enrolled from the program of Chinese Twin Registry, between 2001 and 2002. We used 90 cm of waist circumference in male and 80 cm in female as cut-off values of central obesity. The LPL gene T+495G polymorphism was analyzed with the use of genomic polymerase chain reaction and HindIII-restriction fragment length polymorphism. Two statistical methods were performed to test the effect of T+495G polymorphism of LPL gene on the relation between central obesity and lipid levels: one was the generalized estimating equation model for all twin pairs and the other was co-twin matched case-control analysis in 82 central obesity discordant monozygotic twin pairs. In male twins, central obesity was significantly associated with serum lipids except for high-density lipoprotein (HDL). In female twins, obesity twins had significantly higher levels of triglyceride (TG) and TG/HDL than nonobesity twins. There was no significant association between T+495G polymorphism and lipid levels for all twins, although +495G allele carrier was related with 6.7% decrease of TG was observed only in female twins. The interactions of T+495G polymorphism and central obesity were not found for TG, HDL, and TG/HDL. In central obesity discordant monozygotic twin pairs, central obesity was significantly related with 24.2%, 26.1%, and 4.1% increase of TG ,TG/HDL, and TC, respectively, in +495T/T genotype. These results suggest no association and interaction of T+495G polymorphism with central obesity and serum lipids for all twin pairs. Meanwhile, a modest genetic-environmental effect of T+495G polymorphism and central obesity was found in discordant monozygotic twin pairs. Therefore, the +495T/T genotype may be an independent risk factor associated with central obesity and lipids level. However, the role of LPL gene T+195G polymorphism in central obesity and dyslipidemia is complex and remains controversial. This hypothesis needs further investigation.

Crossed cerebral lateralization for verbal and visuo‐spatial function in a pair of handedness discordant monozygotic twins: MRI and fMRI brain imaging

To examine the nature of hemispheric lateralization for neural processes underlying verbal fluency and visuo-spatial attention, we investigated a single pair of handedness discordant monozygotic (MzHd) twins. Imaging of the brain was undertaken using magnetic resonance imaging (MRI) and functional magnetic resonance imaging (fMRI) in combination with manual performance tasks. The twins were discordant for MRI anatomical asymmetries of the pars triangularis and planum temporale, whose asymmetry was consistent with verbal laterality on fMRI. Thus, the right-handed twin had left lateralized verbal with right lateralized visuo-spatial attention, while the left-handed twin had right lateralized verbal with left lateralized visuo-spatial activation; these data lend further support for to the conclusions of Sommer et al.

Selective Cerebral Volume Reduction in Rett Syndrome: A Multiple-Approach MR Imaging Study

Previous studies have examined volumetric abnormalities in Rett syndrome (RTT), using MR imaging and focusing on selective changes. However, these studies preceded the identification of MECP2 as the gene mutated in most RTT cases. We studied regional brain volume changes as noted by MR imaging in girls with RTT who had mutations in the MECP2 gene and more or less severe clinical outcomes to further characterize the neuroanatomy of RTT and its correlations with clinical severity. Complementary semiautomated Talairach- and voxel-based approaches were used to study spoiled gradient-recalled acquisition sequence MR imaging scans from 23 girls with MECP2 mutations/RTT, including a pair of discordant monozygotic twins and 25 age-matched control girls. Both absolute and relative volumetric changes were examined to account for the well-documented global reduction in brain volume seen in RTT. Absolute volumetric reductions were observed throughout the brain in RTT. Selective/relative decreases in parietal lobe gray matter, particularly in the dorsal parietal region, and mild, diffuse reductions in cortical white matter were observed in the RTT group compared with control subjects. In girls with RTT and a more severe phenotype, anterior frontal lobe volumes were relatively more reduced. Twin comparisons revealed selective preservation of the occipital cortex. Selective reductions of dorsal parietal gray matter and preservation of the occipital cortex seem to be basic neuroanatomic features of RTT, whereas preferential reduction of the anterior frontal lobe appears to be a correlate of clinical severity in this disorder. The most affected brain regions include those that may underlie key functional deficits observed in RTT.

Body mass index, alcohol, tobacco and symptomatic gallstone disease: a Swedish twin study

Both genetic and environmental factors are involved in the pathogenesis of gallstone disease (GD). We aimed to examine the association between symptomatic GD and overweight (body mass index, BMI, 25-30 kg m(-2)), obesity (BMI > 30 kg m(-2)), alcohol, smoking and smoke-free tobacco by analysing a large twin population. The Swedish Twin Registry (STR) was linked to the Swedish Hospital Discharge and Causes of Death Registries for GD and GD-surgery related diagnoses. Weight, height, use of alcohol, smoking and smoke-free tobacco were provided by STR and analysed for possible associations by conditional logistic regression. Overweight and obesity were associated with a significantly higher risk for symptomatic GD in the whole study population (OR 1.86 and OR 3.38; CI: 1.52-2.28 and 2.28-5.02 respectively). High alcohol consumption was associated with a lower risk for GD in the whole population (OR 0.62; CI: 0.51-0.74) with no difference between discordant monozygotic and dizygotic twins (OR 1.08 and OR 0.96; CI: 0.82-1.42 and 0.79-1.16). Smoking or smoke-free tobacco was not correlated with GD. Consistent with epidemiological studies, we found positive associations between BMI and the development of symptomatic GD. High alcohol consumption was associated with a decreased risk against GD. Tobacco use has no impact on GD.

A structural MRI study in monozygotic twins concordant or discordant for attention/hyperactivity problems: Evidence for genetic and environmental heterogeneity in the developing brain

Several structural brain abnormalities have been reported in patients with Attention Deficit Hyperactivity Disorder (ADHD). However, the etiology of these brain changes is still unclear. To investigate genetic and environmental influences on ADHD related neurobiological changes, we performed Voxel-Based Morphometry on MRI scans from monozygotic (MZ) twins selected from a large longitudinal population database to be highly concordant or highly discordant for ratings on the Child Behavior Checklist Attention Problem scale (CBCL-AP). Children scoring low on the CBCL-AP are at low risk for ADHD, whereas children scoring high on this scale are at high-risk for ADHD. Brain differences between concordant high-risk twin pairs and concordant low-risk twin pairs likely reflect the genetic risk for ADHD; brain differences between the low-risk and high-risk twins from discordant MZ twin pairs reflect the environmental risk for ADHD. A major difference between comparisons of high and low-risk twins from concordant pairs and high/low twins from discordant pairs was found for the prefrontal lobes. The concordant high-risk pairs showed volume loss in orbitofrontal subdivisions. High-risk members from the discordant twin pairs exhibited volume reduction in the right inferior dorsolateral prefontal cortex. In addition, the posterior corpus callosum was compromised in concordant high-risk pairs, only. Our findings indicate that inattention and hyperactivity symptoms are associated with anatomical abnormalities of a distributed action-attentional network. Different brain areas of this network appear to be affected in inattention/hyperactivity caused by genetic (i.e., high concordant MZ pairs) vs. environmental (i.e., high-low discordant MZ pairs) risk factors. These results provide clues that further our understanding of brain alterations in ADHD.

Genetic overlap between bipolar illness and event-related potentials

Electrophysiological endophenotypes are far less explored in bipolar disorder as compared to schizophrenia. No previous twin study of event-related potentials (ERPs) in bipolar illness has been reported. This study uses a twin design and advanced genetic model fitting analyses aiming to (1) assess and quantify the relationship of a range of ERP components with bipolar disorder with psychotic features, and (2) examine the source of the relationship (due to genetic or environmental factors). P300, P50 suppression and mismatch negativity (MMN) were recorded in 10 discordant monozygotic (MZ) bipolar twin pairs, six concordant MZ bipolar twin pairs and 78 control twin pairs. Statistical analyses were based on structural equation modelling. Bipolar disorder was significantly associated with smaller P300 amplitude and decreased P50 suppression. Genetic correlations were the main source of the associations, estimated to be -0 x 33 for P300 amplitude and 0 x 46 for P50 ratio. Individual-specific environmental influences were not significant. MMN and P300 latency were not associated with the illness. The results provide supporting evidence that P300 amplitude and P50 suppression ratio are ERP endophenotypes for bipolar disorder.

Lipoprotein lipase gene S447X polymorphism modulates the relation between central obesity and serum lipids, a twin study

To investigate the impact of lipoprotein lipase (LPL) gene S447X polymorphism on the relation between central obesity and lipid levels. A total of 961 adult twin pairs were included from the program of Chinese Twin Registry, between 2001 and 2002. Central obesity was defined as waist circumference > or =90 cm for male and > or =80 cm for female. Two statistical methods were performed to test the modification effect of S447X polymorphism of LPL gene on the relation between central obesity and lipid levels: one was Generalized Estimating Equation (GEE) models for all twin pairs and the other was co-twin matched case-control analysis in 82 central obesity discordant monozygotic twin pairs. In GEE models for all twins, central obesity was significantly associated with serum lipids except for high-density lipoprotein (HDL), while X447 allele had favorable effects on the levels of triglyceride (TG), HDL and TG to HDL ratio (TG/HDL). The interactions of S447X polymorphism and central obesity were statistically significant for TG/HDL and HDL. In central obesity discordant monozygotic twin pairs, central obesity was significantly related with 26.2% increase of TG and 27.2% increase of TG/HDL in S/S447 genotype, while in 447X allele carrier, central obesity was significantly related with 13.7% increase of HDL. These results suggest that LPL gene S447X polymorphism modifies the relation between central obesity and serum lipids, which also stresses the importance of reducing waist circumference to improve serum lipids for people with central obesity, especially those with S/S447 genotype.