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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 -
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 -
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 -
Psychological Medicine Nov 2023Are genetic risk factors for current depressive symptoms good proxies for genetic risk factors for syndromal major depression (MD)?
BACKGROUND
Are genetic risk factors for current depressive symptoms good proxies for genetic risk factors for syndromal major depression (MD)?
METHODS
In over 9000 twins from the population-based Virginia Adult Twin Study of Psychiatric and Substance Use Disorders, the occurrence of all nine DSM symptomatic criteria for MD in the last year was assessed at personal interview and then grouped by their temporal co-occurrence. The DSM criteria which occurred outside (OUT) inside of (IN) MD episodes were then separated. We calculated tetrachoric correlations for OUT and IN depressive criteria in monozygotic (MZ) and dizygotic (DZ) pairs and fitted univariate and bivariate ACE twin models using OpenMx.
RESULTS
The mean twin correlations (±95% CIs) for IN depressive criteria were substantially higher than for OUT depressive criteria in both MZ [+0.35 (0.32-0.38) 0.20 (0.17-0.24)] and DZ pairs [0.20 (0.17-0.24) 0.10 (0.04-0.16]. The mean IN-OUT cross-correlation in MZ and DZ pairs was modest [+0.15 (0.07-0.24) and +0.07 (0.03-0.12)]. The mean heritability estimates for the nine In Out depressive criteria was 0.31 (0.22-0.41) and 0.15 (0.08-0.21), in MZ and DZ pairs, respectively. The mean genetic correlation between the nine IN and OUT depressive criteria was +0.07 (-0.07 to 0.21).
CONCLUSIONS
Depressive criteria occurring outside depressive episodes are less heritable than those occurring within. These two ways criteria can manifest are not closely genetically related. Current depressive symptoms - most of which are occurring outside of depressive episodes - are not, for genetic studies, good proxies for MD.
Topics: Adult; Humans; Depressive Disorder, Major; Depression; Twins, Monozygotic; Twins, Dizygotic; Diseases in Twins
PubMed: 37154209
DOI: 10.1017/S0033291723001241 -
The Journal of Maternal-fetal &... Dec 2023Strong evidence imply that delayed cord clamping (DCC) provides significant benefits for singleton neonates. However, there is little information about the safety or...
OBJECTIVES
Strong evidence imply that delayed cord clamping (DCC) provides significant benefits for singleton neonates. However, there is little information about the safety or efficacy of DCC in twins to recommend for or against DCC in twins in guidelines. We aimed to determine the effect of DCC on dichorionic twins born at <32 weeks of gestation.
STUDY DESIGN
This is a retrospective cohort study comparing the neonatal and maternal outcomes of immediate cord clamping (ICC) [<15 second (s)] versus DCC (at 60 s). Generalized estimating equations models were performed accounting for twin correlation
RESULTS
A total of 82 pairs of twins (DCC: 41; ICC: 41) were included in analysis. The primary outcome of death before discharge occurred in 3.66% of twins in the DCC group and 7.32% in the ICC group, without a significant difference between the groups. Compared to ICC group, DCC was associated with increased hemoglobin levels [β1 coefficient 6.51; 95% confidence interval (CI) 0.69-12.32. β2 coefficient 5.80; 95% CI 0.07-11.54] at 12-24 h of life. There were no significant differences between the groups in neonatal death, neonatal major morbidities and maternal bleeding complications, although DCC was associated with higher estimated maternal blood loss in the cesarean section group ( = .005).
CONCLUSIONS
DCC for 60 s in dichorionic twins born at <32 weeks of gestation was associated with increased neonatal hemoglobin levels, when compared with ICC. The finding of a higher estimated maternal blood loss by cesarean section in the DCC group calls for further trials to assess maternal safety of this procedure in this patient population.
Topics: Infant, Newborn; Pregnancy; Humans; Female; Cesarean Section; Retrospective Studies; Umbilical Cord Clamping; Umbilical Cord; Twins, Dizygotic; Constriction; Hemoglobins
PubMed: 37120713
DOI: 10.1080/14767058.2023.2203300 -
Cancer Epidemiology, Biomarkers &... Nov 2023What are the major determinants of women's breast cancer risk? Rare mutations such as those in the BRCA1/2 genes, polygenic scores of common alleles identified by...
BACKGROUND
What are the major determinants of women's breast cancer risk? Rare mutations such as those in the BRCA1/2 genes, polygenic scores of common alleles identified by genome-wide association studies, or nongenetic factors?
METHODS
The population-based Nordic Twin Study of Cancer, with 3,933 breast cancer cases among 21,054 monozygotic (MZ) and 30,939 dizygotic (DZ) female twin pairs, provides three key clues to this question: (i) the average lifetime risk, approximately 8%, does not differ by twin zygosity; (ii) the mean time interval between diagnoses when both twins develop disease (i.e., disease concordance) also does not differ by zygosity; but, (iii) conditioning on one twin having developed disease, the incidence rate in the co-twin is approximately 1% per year if the pair is MZ and 0.5% per year if DZ.
RESULTS
Assuming that nongenetic risk factors are shared similarly between twins regardless of zygosity, we can draw two conclusions from (i) to (iii).
CONCLUSIONS
First, (i) and (iii) imply that the chief determinant of risk is in the germline DNA, because the conditional incidence rate is several-fold higher than the average risk (8% lifetime) in MZ twins but only half as much in DZ twins. Second, the seeming inconsistency between the two-fold conditional incidence rate (iii) and the equality of the mean inter-twin disease intervals in disease concordance (ii) can be resolved if the risk factors in the germline DNA are rare variants, not common variants.
IMPACT
This paper details simple deductive reasoning for these conclusions and draws a critical inference regarding breast cancer etiology. See related In the Spotlight, p. 1477.
Topics: Humans; Female; BRCA1 Protein; Breast Neoplasms; Genome-Wide Association Study; BRCA2 Protein; Twins, Monozygotic; Twins, Dizygotic; Diseases in Twins; Risk Factors; DNA
PubMed: 36652676
DOI: 10.1158/1055-9965.EPI-22-1073 -
Human Brain Mapping Nov 2023We propose a unique, minimal assumption, approach based on variance analyses (compared with standard approaches) to investigate genetic influence on individual...
We propose a unique, minimal assumption, approach based on variance analyses (compared with standard approaches) to investigate genetic influence on individual differences on the functional connectivity of the brain using 65 monozygotic and 65 dizygotic healthy young adult twin pairs' low-frequency oscillation resting state functional Magnetic Resonance Imaging (fMRI) data from the Human Connectome Project. Overall, we found high number of genetically-influenced functional (GIF) connections involving posterior to posterior brain regions (occipital/temporal/parietal) implicated in low-level processes such as vision, perception, motion, categorization, dorsal/ventral stream visuospatial, and long-term memory processes, as well as high number across midline brain regions (cingulate) implicated in attentional processes, and emotional responses to pain. We found low number of GIF connections involving anterior to anterior/posterior brain regions (frontofrontal > frontoparietal, frontotemporal, frontooccipital) implicated in high-level processes such as working memory, reasoning, emotional judgment, language, and action planning. We found very low number of GIF connections involving subcortical/noncortical networks such as basal ganglia, thalamus, brainstem, and cerebellum. In terms of sex-specific individual differences, individual differences in males were more genetically influenced while individual differences in females were more environmentally influenced in terms of the interplay of interactions of Task positive networks (brain regions involved in various task-oriented processes and attending to and interacting with environment), extended Default Mode Network (a central brain hub for various processes such as internal monitoring, rumination, and evaluation of self and others), primary sensorimotor systems (vision, audition, somatosensory, and motor systems), and subcortical/noncortical networks. There were >8.5-19.1 times more GIF connections in males than females. These preliminary (young adult cohort-specific) findings suggest that individual differences in the resting state brain may be more genetically influenced in males and more environmentally influenced in females; furthermore, standard approaches may suggest that it is more substantially nonadditive genetics, rather than additive genetics, which contribute to the differences in sex-specific individual differences based on this young adult (male and female) specific cohort. Finally, considering the preliminary cohort-specific results, based on standard approaches, environmental influences on individual differences may be substantially greater than that of genetics, for either sex, frontally and brain-wide. [Correction added on 10 May 2023, after first online publication: added: functional Magnetic Resonance Imaging. Added: individual differences in, twice. Added statement between furthermore … based on standard approaches.].
Topics: Female; Humans; Male; Young Adult; Basal Ganglia; Brain; Brain Mapping; Connectome; Magnetic Resonance Imaging; Nerve Net; Thalamus; Twins, Dizygotic
PubMed: 36537283
DOI: 10.1002/hbm.25947 -
Stressful life events increase the risk of major depressive episodes: A population-based twin study.Psychological Medicine Aug 2023Previous studies have found that stressful life events (SLEs) are associated with an increased risk of adult depression. However, many studies are observational in...
BACKGROUND
Previous studies have found that stressful life events (SLEs) are associated with an increased risk of adult depression. However, many studies are observational in nature and limited by methodological issues, such as potential confounding by genetic factors. Genetically informative research, such as the co-twin control design, can strengthen causal inference in observational studies. Discrete-time survival analysis has several benefits and multilevel survival analysis can incorporate frailty terms (random effects) to estimate the components of the biometric model. In the current study, we investigated associations between SLEs and depression risk in a population-based twin sample ( = 2299).
METHODS
A co-twin control design was used to investigate the influence of the occurrence of SLEs on depression risk. The co-twin control design involves comparing patterns of associations in the full sample and within dizygotic (DZ) and monozygotic twins (MZ). Associations were modelled using discrete-time survival analysis with biometric frailty terms. Data from two time points were used in the analyses. Mean age at Wave 1 was 28 years and mean age at Wave 2 was 38 years.
RESULTS
SLE occurrence was associated with increased depression risk. Co-twin control analyses indicated that this association was at least in part due to the causal influence of SLE exposure on depression risk for event occurrence across all SLEs and for violent SLEs. A minor proportion of the total genetic risk of depression reflected genetic effects related to SLEs.
CONCLUSIONS
The results support previous research in implicating SLEs as important risk factors with probable causal influence on depression risk.
Topics: Adult; Humans; Depressive Disorder, Major; Frailty; Life Change Events; Diseases in Twins; Twins, Monozygotic; Risk Factors; Twins, Dizygotic
PubMed: 35920242
DOI: 10.1017/S0033291722002227