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Investigative Ophthalmology & Visual... Jul 2023The relative importance of genetic factors in common vitreomacular interface (VMI) abnormalities is unknown. The aim of this classical twin study is to determine the...
PURPOSE
The relative importance of genetic factors in common vitreomacular interface (VMI) abnormalities is unknown. The aim of this classical twin study is to determine the prevalence case wise concordance between monozygotic and dizygotic twin pairs, and heritability of common VMI abnormalities, including epiretinal membrane (ERM), posterior vitreous detachment (PVD), vitreomacular adhesion (VMA), vitreomacular traction (VMT), lamellar macular holes (LMHs), and full-thickness macular holes (FTMHs).
METHODS
This is a single-center, cross-sectional classical twin study of 3406 TwinsUK participants over the age of 40 years who underwent spectral domain macular optical coherence tomography (SD-OCT) scans which were graded for signs of VMI abnormalities. Case wise concordance was calculated and the heritability of each VMI abnormality was estimated using OpenMx structural equation modeling.
RESULTS
In this population (mean age = 62.0 years [SD = 10.4 years], range = 40-89 years) the overall prevalence of ERM was 15.6% (95% confidence interval [CI] = 14.4-16.9) and increased with age, posterior vitreous detachment affected 21.3% (20.0-22.7), and VMA was diagnosed in 11.8% (10.8-13.0). Monozygotic twins were more concordant for all traits than dizygotic twins, and age, spherical equivalent refraction (SER), and lens status-adjusted heritability was estimated at 38.9% (95% CI = 33.6-52.8) for ERM, 53.2% (95% CI = 41.8-63.2) for PVD, and 48.1% (95% CI = 33.6-58) for VMA.
CONCLUSIONS
Common VMI abnormalities are heritable and therefore have an underlying genetic component. Given the sight-threatening potential of VMI abnormalities, further genetic studies, such as genomewide association studies, would be useful to identify genes and pathways implicated in their pathogenesis.
Topics: Humans; Adult; Middle Aged; Aged; Aged, 80 and over; Vitreous Detachment; Retinal Perforations; Vitreous Body; Prevalence; Cross-Sectional Studies; Retinal Diseases; Epiretinal Membrane; Orbital Diseases; Tomography, Optical Coherence; Retrospective Studies
PubMed: 37428499
DOI: 10.1167/iovs.64.10.9 -
Indian Heart Journal 2023Rheumatic fever and RHD constitutes an important public health problem in India. The relatively low attack rate of RF, the high concordance rate for RF in monozygotic...
INTRODUCTION
Rheumatic fever and RHD constitutes an important public health problem in India. The relatively low attack rate of RF, the high concordance rate for RF in monozygotic twins (19%) compared to dizygotic twins (2.5%), and the high familial incidence of RF suggest the involvement of host genetic factors in susceptibility to RF with consequential progression to RHD.
OBJECTIVE
To study the association of HLA CLASS II DR/DQ alleles in children and adolescents with RHD from a tertiary care center in North India.
METHODS
30 RHD patients and 30 age and sex-matched controls were included in our study and blood samples for HLA typing were processed through LAB Type™ reverse SSO DNA typing method. The assignment of the HLA typing was based on a comparison with already published HLA gene sequences.
RESULTS
The mean age of RHD patients and matched control groups were 12.97 ± 2.95 and 11.93 ± 3.23, respectively. In the cases and control group, males accounted for 63.3% and 50% of the patients respectively. A significant difference was found between the cases and controls for HLA DR∗ 15 (p-value 0.002), HLA DR∗ B4 (p-value 0.045), HLA DR∗ B5 (p-value 0.017), and HLA DQB1∗ 02 (p-value 0.005).
CONCLUSION
Our study suggests that HLA class II haplotypes may provide insight into the molecular mechanism of RHD and be a useful tool in predicting the clinical outcome in RF patients, thereby affording new means of intervention or vaccine design. Larger studies are needed to address this in our population.
Topics: Male; Humans; Child; Adolescent; Rheumatic Heart Disease; Tertiary Care Centers; Alleles; Genetic Predisposition to Disease; Gene Frequency; HLA-DR Antigens; India
PubMed: 37406855
DOI: 10.1016/j.ihj.2023.06.008 -
Journal of the American Academy of... Jan 2024White matter alterations are frequently reported in autism spectrum disorder (ASD), yet the etiology is currently unknown. The objective of this investigation was to...
OBJECTIVE
White matter alterations are frequently reported in autism spectrum disorder (ASD), yet the etiology is currently unknown. The objective of this investigation was to examine, for the first time, the impact of genetic and environmental factors on white matter microstructure in twins with ASD compared to control twins without ASD.
METHOD
Diffusion-weighted MRIs were obtained from same-sex twin pairs (6-15 years of age) in which at least 1 twin was diagnosed with ASD or neither twin exhibited a history of neurological or psychiatric disorders. Fractional anisotropy (FA) and mean diffusivity (MD) were examined across different white matter tracts in the brain, and statistical and twin modeling were completed to assess the proportion of variation associated with additive genetic (A) and common/shared (C) or unique (E) environmental factors. We also developed a novel Twin-Pair Difference Score analysis method that produces quantitative estimates of the genetic and environmental contributions to shared covariance between different brain and behavioral traits.
RESULTS
Good-quality data were available from 84 twin pairs, 50 ASD pairs (32 concordant for ASD [16 monozygotic; 16 dizygotic], 16 discordant for ASD [3 monozygotic; 13 dizygotic], and 2 pairs in which 1 twin had ASD and the other exhibited some subthreshold symptoms [1 monozygotic; 1 dizygotic]) and 34 control pairs (20 monozygotic; 14 dizygotic). Average FA and MD across the brain, respectively, were primarily genetically mediated in both control twins (A = 0.80, 95% CI [0.57, 1.02]; A = 0.80 [0.55, 1.04]) and twins concordant for having ASD (A = 0.71 [0.33, 1.09]; A = 0.84 [0.32,1.36]). However, there were also significant tract-specific differences between groups. For instance, genetic effects on commissural fibers were primarily associated with differences in general cognitive abilities and perhaps some diagnostic differences for ASD because Twin-Pair Difference-Score analysis indicated that genetic factors may have contributed to ∼40% to 50% of the covariation between IQ scores and FA of the corpus callosum. Conversely, the increased impact of environmental factors on some projection and association fibers were primarily associated with differences in symptom severity in twins with ASD; for example, our analyses suggested that unique environmental factors may have contributed to ∼10% to 20% of the covariation between autism-related symptom severity and FA of the cerebellar peduncles and external capsule.
CONCLUSION
White matter alterations in youth with ASD are associated with both genetic contributions and potentially increased vulnerability or responsivity to environmental influences.
DIVERSITY & INCLUSION STATEMENT
We worked to ensure sex and gender balance in the recruitment of human participants. We worked to ensure race, ethnic, and/or other types of diversity in the recruitment of human participants. We worked to ensure that the study questionnaires were prepared in an inclusive way. One or more of the authors of this paper self-identifies as a member of one or more historically underrepresented racial and/or ethnic groups in science. One or more of the authors of this paper self-identifies as a member of one or more historically underrepresented sexual and/or gender groups in science. One or more of the authors of this paper self-identifies as living with a disability. The author list of this paper includes contributors from the location and/or community where the research was conducted and they participated in the data collection, design, analysis, and/or interpretation of the work.
Topics: Male; Female; Humans; Adolescent; Autism Spectrum Disorder; White Matter; Twins, Monozygotic; Brain; Autistic Disorder
PubMed: 37406770
DOI: 10.1016/j.jaac.2023.05.030 -
Frontiers in Genetics 2023Assortative mating refers describes a phenomenon in which individuals with similar phenotypic traits are more likely to mate and reproduce with each other; i.e....
Assortative mating refers describes a phenomenon in which individuals with similar phenotypic traits are more likely to mate and reproduce with each other; i.e. assortative mating occurs when individuals choose partners based on their similarity or dissimilarity in certain traits.to patterns of non-random mating of spouses leading to phenotypic resemblance. There are various theories about the its underlying mechanisms, which have different genetic consequences. We analyzed examined two possible mechanisms underlying assortative mating - phenotypic assortment and social homogamy - for educational attainment in two countries utilizing data of mono- and dizygotic twins and their spouses (1,451 Finnish and 1,616 Dutch twin-spouse pairs). The spousal correlations were 0.51 in Finland and 0.45 in the Netherlands, to which phenotypic assortment contributed 0.35 and 0.30, and social homogamy 0.16 and 0.15, respectively. Both social homogamy and phenotypic assortment are important processes in spouse selection in Finland and the Netherlands. In both countries, phenotypic assortment contributes to a greater degree to the similarity of spouses than social homogamy.
PubMed: 37396041
DOI: 10.3389/fgene.2023.1150697 -
JAMA Network Open Jun 2023Low birth weight is associated with an increased likelihood of neurodivergence and neurodevelopmental conditions (NDCs) such as autism, attention-deficit/hyperactivity...
IMPORTANCE
Low birth weight is associated with an increased likelihood of neurodivergence and neurodevelopmental conditions (NDCs) such as autism, attention-deficit/hyperactivity disorder (ADHD), and intellectual disability. However, it is unclear whether birth weight contributes independently to NDCs or whether the association is predominantly driven by genetic predisposition.
OBJECTIVE
To estimate the associations between birth weight and dimensional (trait) and categorical (diagnoses) NDC outcomes, while adjusting for genetic risks.
DESIGN, SETTING, AND PARTICIPANTS
A co-twin design was applied to this case-control study conducted in Sweden. Diagnostic assessments were conducted between August 2011 and March 2022, within the Roots of Autism and ADHD Twin Study in Sweden (RATSS) during a 2.5-day participant visit to the clinic. The RATSS sample comprised phenotyped monozygotic and dizygotic twins enriched for NDCs. Data analysis was conducted in November 2022.
EXPOSURE
Birth weight.
MAIN OUTCOMES AND MEASURES
Categorical and dimensional operationalizations of autism, ADHD, and intellectual disability were assessed. Generalized estimating equation models were fitted across and within twin pairs.
RESULTS
The study sample included 393 twins: 230 were monozygotic and 159 were dizygotic (zygosity was unknown for 4). Their median age was 15 (range, 8-37) years. There were 185 female participants (47.1%) and 208 male participants (52.9%). Across twin pairs, higher birth weight was associated with fewer autistic traits (unstandardized β [B], -5.51 [95% CI, -10.09 to -0.94]) and lower odds of autism diagnosis (OR, 0.63 [95% CI, 0.45 to 0.88]) and intellectual disability (OR, 0.42 [95% CI, 0.19 to 0.92]). Within pairs, the association between birth weight and dimensional autism (B, -17.35 [95% CI, -28.66 to -6.04]) and categorical autism (OR, 0.02 [95% CI, 0.001 to 0.42]) remained among monozygotic pairs but not dizygotic pairs. In addition, higher birth weight was associated with lower odds of ADHD diagnosis (OR, 0.003 [95% CI, 0 to 0.70]), fewer ADHD traits (B, -0.25 [95% CI, -0.39 to -0.11]), and higher IQ ratings (B, 7.43 [95% CI, 1.05 to 13.82]) among monozygotic twins.
CONCLUSIONS AND RELEVANCE
The findings of this co-twin study suggest an association between low birth weight and NDCs, but they also acknowledge the importance of genetics because the associations observed were only statically significant among monozygotic twins. It is of pivotal importance to facilitate early identification of factors contributing to fetal growth restriction to minimize detrimental outcomes.
Topics: Adolescent; Female; Humans; Male; Birth Weight; Case-Control Studies; Intellectual Disability; Risk Factors; Twins, Dizygotic; Child; Young Adult; Adult
PubMed: 37389871
DOI: 10.1001/jamanetworkopen.2023.21165 -
Scientific Reports Jun 2023We aimed to investigate transitions to and from sickness absence, or disability pension among individuals with back, neck, or shoulder pain and/or with common mental...
We aimed to investigate transitions to and from sickness absence, or disability pension among individuals with back, neck, or shoulder pain and/or with common mental disorders (CMDs), and the role of familial (genetics and shared environment) influences on the transitions. Swedish twins born 1935-1985 who responded to pain and CMDs survey items (N = 41,516) were followed on average 8.7 years for sickness absence states in national registers. Multi-state Cox regression models were applied for three exposure groups: pain, CMDs, and presence of both, compared to unexposed. Exposure discordant twin pairs, stratified by zygosity, were analysed to assess the role of familial factors. Hazard Ratios (HR) with 95% confidence intervals and transition intensities were calculated. HRs were similar for transitions between states among those with pain or CMDs. The highest HRs were for transitions from entry to sickness absence and sickness absence to disability pension among those with both pain and CMDs (HRs: 1.61 and 1.43, respectively). Higher HRs for dizygotic compared to monozygotic twins for the first transition to sickness absence and for altering back to not being sickness absent indicate familial confounding. Back, neck, or shoulder pain and/or CMDs indicate a higher risk to become sickness absent and for repeated sickness absence episodes over time compared to unaffected.
Topics: Humans; Shoulder Pain; Sweden; Twins, Monozygotic; Neck; Mental Disorders
PubMed: 37386053
DOI: 10.1038/s41598-023-37572-5 -
Perspectives on Psychological Science :... Nov 2023What are the major sources of worldwide variability in subjective well-being (SWB)? Twin and family studies of SWB have found substantial heritability and strong effects...
What are the major sources of worldwide variability in subjective well-being (SWB)? Twin and family studies of SWB have found substantial heritability and strong effects from unique environments but virtually no effects from shared environments. However, extant findings are not necessarily valid at the global level. Prior studies have examined within-countries variability but did not take into account mean differences across nations. In this article, we aim to estimate the effects of genetic factors, individual environmental exposures, and shared environments for the global population. We combine a set of knowns from national well-being studies (means and standard deviations) and behavioral-genetic studies (heritability) to model a scenario of twin studies across 157 countries. For each country, we simulate data for a set of twin pairs and pool the data into a global sample. We find a worldwide heritability of 31% to 32% for SWB. Individual environmental factors explain 46% to 52% of the variance (including measurement error), and shared environments account for 16% to 23% of the global variance in SWB. Worldwide, well-being is somewhat less heritable than within nations. In contrast to previous within-countries studies, we find a notable effect of shared environments. This effect is not limited to within families but operates at a national level.
Topics: Humans; Twins, Dizygotic; Twins, Monozygotic; Environmental Exposure; Gene-Environment Interaction; Genetics
PubMed: 37384562
DOI: 10.1177/17456916231178716 -
Translational Psychiatry Jun 2023The first systematic review and meta-analysis of obsessive-compulsive disorder (OCD) genetic epidemiology was published approximately 20 years ago. Considering the... (Meta-Analysis)
Meta-Analysis
The first systematic review and meta-analysis of obsessive-compulsive disorder (OCD) genetic epidemiology was published approximately 20 years ago. Considering the relevance of all the studies published since 2001, the current study aimed to update the state-of-art knowledge on the field. All published data concerning the genetic epidemiology of OCD from the CENTRAL, MEDLINE, EMBASE, BVS, and OpenGrey databases were searched by two independent researchers until September 30, 2021. To be included, the articles had to fulfill the following criteria: OCD diagnosis provided by standardized and validated instruments; or medical records; inclusion of a control group for comparison and case-control, cohort or twin study designs. The analysis units were the first-degree relatives (FDRs) of OCD or control probands and the co-twins in twin pairs. The outcomes of interest were the familial recurrence rates of OCD and the correlations of OCS in monozygotic compared with dizygotic twins. Nineteen family, twenty-nine twin, and six population-based studies were included. The main findings were that OCD is a prevalent and highly familial disorder, especially among the relatives of children and adolescent probands, that OCD has a phenotypic heritability of around 50%; and that the higher OCS correlations between MZ twins were mainly due to additive genetic or to non-shared environmental components.
Topics: Adolescent; Child; Humans; Molecular Epidemiology; Twins, Dizygotic; Databases, Factual; Research Design
PubMed: 37380645
DOI: 10.1038/s41398-023-02433-2 -
Frontiers in Endocrinology 2023Pregnancy-associated plasma protein-A (PAPP-A) is an IGF-activating enzyme suggested to influence aging-related diseases. However, knowledge on serum PAPP-A...
INTRODUCTION
Pregnancy-associated plasma protein-A (PAPP-A) is an IGF-activating enzyme suggested to influence aging-related diseases. However, knowledge on serum PAPP-A concentration and regulation in elderly subjects is limited. Therefore, we measured serum PAPP-A in elderly same-sex monozygotic (MZ) and dizygotic (DZ) twins, as this allowed us to describe the age-relationship of PAPP-A, and to test the hypothesis that serum PAPP-A concentrations are genetically determined. As PAPP-A is functionally related to stanniocalcin-2 (STC2), an endogenous PAPP-A inhibitor, we included measurements on STC2 as well as IGF-I and IGF-II.
METHODS
The twin cohort contained 596 subjects (250 MZ twins, 346 DZ twins), whereof 33% were males. The age ranged from 73.2 to 94.3 (mean 78.8) years. Serum was analyzed for PAPP-A, STC2, IGF-I, and IGF-II by commercial immunoassays.
RESULTS
In the twin cohort, PAPP-A increased with age (r=0.19; 0.05), whereas IGF-I decreased (r=-0.12; 0.05). Neither STC2 nor IGF-II showed any age relationship. When analyzed according to sex, PAPP-A correlated positively with age in males (r=0.18; 0.05) and females (r=0.25; 0.01), whereas IGF-I correlated inversely in females only (r=-0.15; 0.01). Males had higher levels of PAPP-A (29%), STC2 (18%) and IGF-I (19%), whereas serum IGF-II was 28% higher in females (all 0.001). For all four proteins, within-pair correlations were significantly higher for MZ twins than for DZ twins, and they demonstrated substantial and significant heritability, which after adjustment for age and sex averaged 59% for PAPP-A, 66% for STC2, 58% for IGF-I, and 52% for IGF-II.
DISCUSSION
This twin study confirms our hypothesis that the heritability of PAPP-A serum concentrations is substantial, and the same is true for STC2. As regards the age relationship, PAPP-A increases with age, whereas STC2 remains unchanged, thereby supporting the idea that the ability of STC2 to inhibit PAPP-A enzymatic activity decreases with increasing age.
Topics: Male; Female; Humans; Aged; Aged, 80 and over; Insulin-Like Growth Factor I; Insulin-Like Growth Factor II; Pregnancy-Associated Plasma Protein-A; Twins, Dizygotic; Peptide Hormones
PubMed: 37334305
DOI: 10.3389/fendo.2023.1193742 -
Psychological Medicine Apr 2023Recent well-powered genome-wide association studies have enhanced prediction of substance use outcomes via polygenic scores (PGSs). Here, we test (1) whether these...
Associations between polygenic risk of substance use and use disorder and alcohol, cannabis, and nicotine use in adolescence and young adulthood in a longitudinal twin study.
BACKGROUND
Recent well-powered genome-wide association studies have enhanced prediction of substance use outcomes via polygenic scores (PGSs). Here, we test (1) whether these scores contribute to prediction over-and-above family history, (2) the extent to which PGS prediction reflects inherited genetic variation demography (population stratification and assortative mating) and indirect genetic effects of parents (genetic nurture), and (3) whether PGS prediction is mediated by behavioral disinhibition prior to substance use onset.
METHODS
PGSs for alcohol, cannabis, and nicotine use/use disorder were calculated for Minnesota Twin Family Study participants ( = 2483, 1565 monozygotic/918 dizygotic). Twins' parents were assessed for histories of substance use disorder. Twins were assessed for behavioral disinhibition at age 11 and substance use from ages 14 to 24. PGS prediction of substance use was examined using linear mixed-effects, within-twin pair, and structural equation models.
RESULTS
Nearly all PGS measures were associated with multiple types of substance use independently of family history. However, most within-pair PGS prediction estimates were substantially smaller than the corresponding between-pair estimates, suggesting that prediction is driven in part by demography and indirect genetic effects of parents. Path analyses indicated the effects of both PGSs and family history on substance use were mediated via disinhibition in preadolescence.
CONCLUSIONS
PGSs capturing risk of substance use and use disorder can be combined with family history measures to augment prediction of substance use outcomes. Results highlight indirect sources of genetic associations and preadolescent elevations in behavioral disinhibition as two routes through which these scores may relate to substance use.
Topics: Child; Adolescent; Humans; Young Adult; Adult; Cannabis; Nicotine; Genome-Wide Association Study; Ethanol; Hallucinogens; Substance-Related Disorders; Cannabinoid Receptor Agonists
PubMed: 37310313
DOI: 10.1017/S0033291721004116