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Background and Objectives: Progressive supranuclear palsy (PSP) is a neurodegenerative disease, a tauopathy, which results in a wide clinical spectrum of neurological symptoms. The diagnosis is mostly based on clinical signs and neuroimaging; however, possible biomarkers for screening have been under investigation, and the role of the gut microbiome is unknown. The aim of our study was to identify potential blood biomarkers and observe variations in the gut microbiome within a PSP discordant monozygotic twin pair. Materials and Methods: Anthropometric measurements, neuropsychological tests, and the neurological state were evaluated. Blood was collected for metabolic profiling and for the detection of neurodegenerative and vascular biomarkers. Both the gut microbiome and brain MRI results were thoroughly examined. Results: We found a relevant difference between alpha-synuclein levels and moderate difference in the levels of MMP-2, MB, Apo-A1, Apo-CIII, and Apo-H. With respect to the ratios, a small difference was observed for ApoA1/SAA and ApoB/ApoA1. Using a microbiome analysis, we also discovered a relative dysbiosis, and the MRI results revealed midbrain and frontoparietal cortical atrophy along with a reduction in overall brain volumes and an increase in white matter lesions in the affected twin. Conclusions: We observed significant differences between the unaffected and affected twins in some risk factors and blood biomarkers, along with disparities in the gut microbiome. Additionally, we detected abnormalities in brain MRI results and alterations in cognitive functions.

Background: Recurrent upper airway obstruction during sleep is a common feature of obstructive sleep apnea (OSA). Risk factors for the development of OSA include obesity, male gender and smoking. In addition, anatomical factors contribute to the development of the disease; however, the heritability of the anatomical structures that determine upper airway narrowing is poorly understood. In this study, we aimed to investigate the background of anatomical structures associated with upper airway narrowing in discordant monozygotic (MZ) twin pairs. Methods: 33 adult MZ twin pairs (median age and Q1-Q3: 50 (42–56) years) from the Hungarian Twin Registry underwent head and neck MR (Philips Ingenia 1.5 T). T1- and T2-weighted images in sagittal, coronal and axial planes were used to measure cephalometric, soft tissue and adipose tissue structures. In addition, the twin pairs underwent carotid and femoral ultrasound scans (Samsung RS85) and full-body composition measurements (OMRON BF500). The analysis of discordant MZ twins for anatomical markers in relation to clinical background, blood test, vascular ultrasound and body composition results was performed using a paired permutation test. Results: We found a significant association between parapharyngeal adipose tissue area and body weight, waist circumference and metabolism (p < 0.05). Submental adipose tissue thickness showed an association with lower body muscle percentage (

Abstract Previous studies suggested cervical spondylosis as a risk factor for development of obstructive sleep apnoea (OSA). We aimed to assess lumbar disc degeneration in patients with OSA and correlate the findings with symptoms and disease severity. Twenty-seven patients with OSA and 29 non-OSA controls underwent sleep studies and lumbar magnetic resonance imaging (MRI), and completed the Epworth Sleepiness Scale and the 24-item Roland‐Morris Disability Questionnaire (RMDQ) questionnaires. Plasma klotho was determined with enzyme-linked immunosorbent assay. Patients with OSA had higher number of disc bulges (4.6 ± 3.7 vs. 1.7 ± 2.5, p 0.05). Markers of OSA severity, including the oxygen desaturation index and percentage of total sleep time spent with saturation

Background: Obstructive sleep apnoea (OSA) and gut dysbiosis are known risk factors for atherosclerosis. However, only very few studies have been focused on the relationship between OSA, atherosclerosis, and the intestinal microbiome, all in animal models. Methods: Twenty-two patients with OSA, 16 with and 6 without carotid atherosclerosis were involved in the study. After a diagnostic sleep examination, the intima media thickness (IMT) was measured and plaques were found using carotid ultrasound. Blood was also drawn for metabolic profile, and a stool sample was provided for 16S ribosomal RNA microbiome investigation. Results: An increased maximal common carotid artery (CCA) IMT was significantly associated with decreased phylum-level diversity. The level of Peptostreptococcaceae was significantly lower in atherosclerotic subjects. Some other candidate microbes appeared in the two groups at the genus level as well: Bilophila, Romboutsia, Slackia, and Veillonella in the non-atherosclerotic group; and Escherichia-Shigella, Prevotella, and Ruminococcaceae in the atherosclerotic group. Conclusions: This is the first pilot research to analyze the association between the gut microbiome and atherosclerosis in adult patients with OSA with and without carotid atherosclerosis. Dysbiosis and individual bacteria may contribute to the development of carotid atherosclerosis in patients with OSA. Further investigations are necessary to reveal a more precise background in a larger sample.

Background and Objectives: Subcortical grey matter structures play essential roles in cognitive, affective, social, and motoric functions in humans. Their volume changes with age, and decreased volumes have been linked with many neuropsychiatric disorders. The aim of our study was to examine the heritability of six subcortical brain volumes (the amygdala, caudate nucleus, pallidum, putamen, thalamus, and nucleus accumbens) and four general brain volumes (the total intra-cranial volume and the grey matter, white matter, and cerebrospinal fluid (CSF) volume) in twins. Materials and Methods: A total of 118 healthy adult twins from the Hungarian Twin Registry (86 monozygotic and 32 dizygotic; median age 50 ± 27 years) underwent brain magnetic resonance imaging. Two automated volumetry pipelines, Computational Anatomy Toolbox 12 (CAT12) and volBrain, were used to calculate the subcortical and general brain volumes from three-dimensional T1-weighted images. Age- and sex-adjusted monozygotic and dizygotic intra-pair correlations were calculated, and the univariate ACE model was applied. Pearson’s correlation test was used to compare the results obtained by the two pipelines. Results: The age- and sex-adjusted heritability estimates, using CAT12 for the amygdala, caudate nucleus, pallidum, putamen, and nucleus accumbens, were between 0.75 and 0.95. The thalamus volume was more strongly influenced by common environmental factors (C = 0.45−0.73). The heritability estimates, using volBrain, were between 0.69 and 0.92 for the nucleus accumbens, pallidum, putamen, right amygdala, and caudate nucleus. The left amygdala and thalamus were more strongly influenced by common environmental factors (C = 0.72−0.85). A strong correlation between CAT12 and volBrain (r = 0.74−0.94) was obtained for all volumes. Conclusions: The majority of examined subcortical volumes appeared to be strongly heritable. The thalamus was more strongly influenced by common environmental factors when investigated with both segmentation methods. Our results underline the importance of identifying the relevant genes responsible for variations in the subcortical structure volume and associated diseases.

Introduction: White matter hyperintensities (WMH) indicate white matter brain lesions in magnetic resonance imaging (MRI), which can be used as a marker for brain aging and cerebrovascular and neurodegenerative disorders. Twin studies revealed substantial but not uniform WMH heritability in elderly twins. The objective of our study was to investigate the genetic and environmental components of WMH, as well as their importance in a healthy twin population, utilizing 3T MRI scanners in a middle-aged twin population. Methods: Brain MRI was performed on 120 healthy adult twins from the Hungarian Twin Registry on a 3T scanner (86 monozygotic, MZ and 34 dizygotic, DZ twins; median age 50 ± 26.5 years, 72.5% female and 27.5% male). The count of WMH on FLAIR images was calculated using an automated volumetry pipeline (volBrain) and human processing. The age- and sex-adjusted MZ and DZ intra-pair correlations were determined and the total variance was decomposed into genetic, shared and unique environmental components using structural equation modeling. Results: Age and sex-adjusted MZ intrapair correlations were higher than DZ correlations, indicating moderate genetic influence in each lesion (rMZ = 0.466, rDZ = −0.025 for total count; rMZ = 0.482, rDZ = 0.093 for deep white matter count; rMZ = 0.739, rDZ = 0.39 for infratentorial count; rMZ = 0.573, rDZ = 0.372 for cerebellar count and rMZ = 0.473, rDZ = 0.19 for periventricular count), indicating a moderate heritability (A = 40.3%, A = 45%, A = 72.7% and A = 55.5%and 47.2%, respectively). The rest of the variance was influenced by unique environmental effects (E between 27.3% and 59.7%, respectively). Conclusions: The number of WMH lesions is moderately influenced by genetic effects, particularly in the infratentorial region in middle-aged twins. These results suggest that the distribution of WMH in various brain regions is heterogeneous.

Introduction: Obstructive sleep apnea (OSA) is a common disorder characterized by the repetitive collapse of the upper airways during sleep, most likely in the oropharyngeal region. Anatomical factors significantly contribute to the disease development; however, the heritability of the upper airway dimensions, which lead to the collapsibility of the upper airways, is less known. In the current study, we aimed to quantify the impact of heritable and environmental factors on the upper airway dimensions in twins using magnetic resonance imaging (MRI). Methods: We completed head and neck MRI imaging on 110 (66 monozygotic and 44 dizygotic, age median and Q1–Q3: 53 (44–63.75) years) adult twins from the Hungarian Twin Registry. We completed cephalometric, soft tissue and fatty tissue space measurements on T1- and T2-weighted images in sagittal, coronal and axial planes. For the analysis of the genetic and environmental, the determination of the measured parameters was performed with an ACE twin statistical model. Results: We found a strong genetic determination in the anteroposterior diameter of the tongue and the thickness of the submental fatty tissue of the neck. Other parameters of the tongue, soft palate and uvula have shown moderate heritability, while we found strong environmental determination in the thickness of the parapharyngeal fatty tissue, the thickness of the pharyngeal wall, and the smallest diameter of the posterior upper airways. Conclusion: Our twin study can help better understand the genetic and environmental background of anatomical structures involved in the development of sleep apnea.

Background: Obstructive sleep apnoea (OSA) is a risk factor for cardiovascular disease. Alterations in the gut microbiome have been implicated in the development of cardiovascular disease and may potentially link OSA to its cardiovascular consequences. However, only one study to date has investigated gut microbiomes in adult patients with OSA. Methods: 19 patients with OSA and 20 non-OSA controls participated in the study. Following a diagnostic sleep study, blood was collected for metabolic profiling, and the subjects provided a stool sample for microbiome analysis. The gut microbiome was investigated using the 16S ribosomal RNA method. Results: Patients with OSA had a higher relative abundance of the Proteobacteria phylum (p = 0.03), Gammaproteobacteria class (p = 0.01), Lactobacillae family (p = 0.02), Lactobacillus (p = 0.03), and Roseburia genus (p = 0.03), and a lower abundance of the Actinobacteria phylum (p = 0.03). The abundance of Proteobacteria, Gammaproteobacteria, Lactobacillae, and Lactobacillus were related to disease severity and dyslipidaemia (all p < 0.05), whilst the abundance of Proteobacteria and Gammaproteobacteria was also related to hypertension and cardiovascular disease (all p < 0.05). However, following adjustment for relevant confounders only the association between OSA and Actinobacteria remained significant (p = 0.04). Conclusions: Obstructive sleep apnoea is associated with only subtle changes in gut microbiome. Further studies should investigate gut dysbiosis in OSA.

Background and Objectives: Aortic arch calcification (AoAC) is associated with a variety of cardiovascular complications. The measurement and grading of AoAC using posteroanterior (PA) chest X-rays are well established. The cardiothoracic ratio (CTR) can be simultaneously measured with PA chest X-rays and used as an index of cardiomegaly. The genetic and environmental contributions to the degree of the AoAC and CTR are not well understood. The purpose of this study was to investigate the effect of genetics and environmental factors on the AoAC and CTR. Materials and Methods: A total of 684 twins from the South Korean twin registry (261 monozygotic, MZ and 81 dizygotic, DZ pairs; mean age 38.6 ± 7.9 years, male/female = 264/420) underwent PA chest X-rays. Cardiovascular risk factors and anthropometric data were also collected. The AoAC and CTR were measured and graded using a standardized method. A structural equation method was used to calculate the proportion of variance explained by genetic and environmental factors behind AoAC and CTR. Results: The within-pair differences were low regarding the grade of AoAC, with only a few twin pairs showing large intra-pair differences. We found that the thoracic width showed high heritability (0.67, 95% CI: 0.59–0.73, p = 1). Moderate heritability was detected regarding cardiac width (0.54, 95% CI: 0.45–0.62, p = 0.572) and CTR (0.54, 95% CI: 0.44–0.62, p = 0.701). Conclusions: The heritable component was significant regarding thoracic width, cardiac width, and the CTR.

Background and objectives: Multivessel atherosclerosis and its genetic background are under-investigated, although atherosclerosis is seldom local and still causes high mortality. Alternative methods to assess coronary calcification (CAC) might incorporate genetic links between different arteries’ atherosclerotic involvement, however, co-occurrences of coronary calcification have not been investigated in twins yet. Materials and Methods: We assessed the heritability of radio morphologically distinct atherosclerotic plaque types in coronary (non-enhanced CT, Agatston score), carotid, and femoral arteries (B-mode ultrasound) in 190 twin subjects (60 monozygotic, 35 dizygotic pairs). Four-segment scores were derived in order to assess the dissemination of the distinct plaque types in the carotid and femoral arteries taking bilaterality into account. We calculated the genetic correlation between phenotypically correlating plaque types in these arteries. Results: CAC and dissemination of calcified plaques in the carotid and femoral arteries (4S_hyper) were moderately heritable (0.67 [95% CI: 0.37–1] and 0.69 [95% CI: 0.38–1], respectively) when adjusted for age and sex. Hypoechoic plaques in the carotid and femoral arteries showed no heritability, while mixed plaques showed intermediate heritability (0.50 [95% CI: 0–0.76]). Age and sex-adjusted phenotypic correlation between CAC and 4segm_hyper was 0.48 [95% CI: 0.30–0.63] and the underlying genetic correlation was 0.86 [95% CI: 0.42–1]. Conclusions: Calcification of atherosclerotic plaques is moderately heritable in all investigated arteries and significant overlapping genetic factors can be attributed to the phenotypical resemblance of coronary and carotid or femoral atherosclerotic calcification. Our findings support the idea of screening extracoronary arteries in asymptomatic individuals. We also propose a hypothesis about primarily carotid-coronary and femoral-coronary atherosclerosis as two distinct genetic predispositions to co-localization.

Background and Objectives: Previous studies have demonstrated that risk of hip fracture is at least partly heritable. The aim of this study was to determine the magnitude of the genetic component of bone mineral density (BMD), using both X-ray and ultrasound assessment at multiple sites. Materials and Methods: 216 adult, healthy Hungarian twins (124 monozygotic, MZ, 92 dizygotic, DZ; mean age 54.2 ± 14.3 years), recruited from the Hungarian Twin Registry with no history of oncologic disease underwent cross-sectional BMD studies. We measured BMD, T- and Z-scores with dual energy X-ray absorptiometry (DEXA) at multiple sites (lumbar spine, femoral neck, total hip and radius). Quantitative bone ultrasound (QUS) was also performed, resulting in a calculated value of estimated bone mineral density (eBMD) in the heel bone. Heritability was calculated using the univariate ACE model. Results: Bone density had a strong genetic component at all sites with estimates of heritability ranging from 0.613 to 0.838 in the total sample. Lumbar BMD and calcaneus eBMD had major genetic components with estimates of 0.828 and 0.838 respectively, and least heritable (0.653) at the total hip. BMD of the radius had also a strong genetic component with an estimate of 0.806. No common environmental effect was found. The remaining variance was influenced by unique environment (0.162 to 0.387). In females only, slightly higher additive genetic estimates were found, especially in the case of the femoral neck and total hip. Conclusion: Bone mineral density is strongly heritable, especially in females at all locations using both DEXA and QUS, which may explain the importance of family history as a risk factor for bone fractures. Unshared environmental effects account for the rest of the variance with slight differences in magnitude across various bone regions, supporting the role of lifestyle in preventing osteoporotic fractures with various efficacy in different bone regions.

Background and Objectives: The asymmetrical vertebral artery (VA) flow and diameter are common findings, which can result in an asymmetrical blood flow in the basilar artery (BA), leading to bending of the artery over time. This study investigated whether the variation of the different vertebrobasilar morphological indices that influence flow characteristics might be inherited. Materials and Methods: We analyzed 200 cerebral magnetic resonance imaging (MRI) scans of healthy Caucasian twins (100 pairs) who underwent time-of-flight MRI. From the scans, we reconstructed the 3D mesh of the posterior circulation from the start of the V4 segment to the basilar tip and subsequently analyzed the morphology of the vertebrobasilar system. The phenotypic covariances of the different morphological parameters were decomposed into heritability (A), shared (C), and unshared (E) environmental effects. Results: 39% of the twins had left dominant VA, while 32.5% had right dominant. In addition, 28.5% were classified as equal. The vertebral artery V4 segment diameter, curvature, and tortuosity were mainly influenced by shared (C) and unshared (E) environmental factors. A moderate heritability was found for the BA length (A: 63%; 95% CI: 45.7–75.2%; E: 37%; 95% CI: 24.8–54.3%) and volume (A: 60.1%; 95% CI: 42.4–73.2%; E: 39.9%; 95% CI: 26.8–57.6%), while the torsion of both arteries showed no heritability and were only influenced by the unshared environment. Conclusions: The length and volume of the BA show a moderate genetical influence. However, most of the measured morphological indices were influenced by shared and unshared factors, which highlight the role of the ever-changing hemodynamic influences shaping the geometry of the vertebrobasilar system.

Background and Objectives: There is an increasing focus on the effect of the gut microbiome on developing atherosclerosis, but there is still no unified standpoint. We aimed to find associations between intestinal microbiome diversity and a marker of subclinical atherosclerosis, the carotid intima-media thickness (IMT). Materials and Methods: Recruited from the Hungarian Twin Registry, 108 monozygotic (MZ) twins (mean age 52.4 ± 14.1 years, 58% female) underwent a comprehensive carotid ultrasound examination (Samsung RS85). Of the 108 MZ twins, 14 pairs (mean age 65 ± 6.4 years, 71% female) discordant for carotid IMT were selected to undergo a stool sample collection. A special stool sampling container was mailed and received from each participant. After DNA extraction, library construction was performed specifically for the V3–V4 hypervariable region of microbial 16S rRNA. Next, the microbiome composition of the samples was determined using Kraken software. Two hypotheses were tested with the exact permutation test: (1) in the group with normal IMT, the Shannon index of the phyla is higher; and (2) the Firmicutes/Bacteroidetes ratio is greater in the group with high IMT values. Furthermore, the abundance of different bacterial strains present at higher and normal IMT was also explored. Statistical analysis was carried out using R software. Results: Increased Firmicutes/Bacteroidetes ratio was associated with increased IMT (mean Firmicutes/Bacteroidetes ratio of IMT > 0.9 and IMT < 0.9 groups: 2.299 and 1.436, respectively; p = 0.031). In the group with normal IMT values, a substantially higher fraction of Prevotellaceae was observed in contrast with subjects having subclinical atherosclerosis. However, there was no significant difference in the alpha diversity between the two groups. Conclusions: The determining role of individual genera and their proportions in the development and progression of atherosclerosis can be assumed. Further studies are needed to clarify if these findings can be used as potential therapeutic targets.