Older Twins Research Articles

Genetic effects on the skin methylome in healthy older twins

Whole-skin DNA methylation variation has been implicated in several diseases, including melanoma, but its genetic basis has not yet been fully characterized. Using bulk skin tissue samples from 414 healthy female UK twins, we performed twin-based heritability and methylation quantitative trait loci (meQTL) analyses for >400,000 DNA methylation sites. We find that the human skin DNA methylome is on average less heritable than previously estimated in blood and other tissues (mean heritability: 10.02%). meQTL analysis identified local genetic effects influencing DNA methylation at 18.8% (76,442) of tested CpG sites, as well as 1,775 CpG sites associated with at least one distal genetic variant. As a functional follow-up, we performed skin expression QTL (eQTL) analyses in a partially overlapping sample of 604 female twins. Colocalization analysis identified over 3,500 shared genetic effects affecting thousands of CpG sites (10,067) and genes (4,475). Mediation analysis of putative colocalized gene-CpG pairs identified 114 genes with evidence for eQTL effects being mediated by DNA methylation in skin, including in genes implicating skin disease such as ALOX12 and CSPG4. We further explored the relevance of skin meQTLs to skin disease and found that skin meQTLs and CpGs under genetic influence were enriched for multiple skin-related genome-wide and epigenome-wide association signals, including for melanoma and psoriasis. Our findings give insights into the regulatory landscape of epigenomic variation in skin.

Association Between Accelerometer-Measured Physical Activity and Mobility Limitations in Twins.

The associations between mobility limitations and device-measured physical activity are sparsely studied. In this study, these associations are studied among community-dwelling older twins. This cross-sectional study utilized data gathered in 2014-2016 for the MOBILETWIN study. Participants were twins born in Finland between 1940 and 1944 (774 participants, mean age 73years). Physical activity was measured with a hip-worn accelerometer. Mobility limitations were assessed with a questionnaire. Individual-level analyses revealed that physical activity was associated with mobility limitations. Participants with severe mobility limitations took 2,637 (SD = 1,747) steps per day, those with some mobility limitations 4,437 (SD = 2,637) steps, and those without mobility limitations 7,074 (SD = 2,931) steps (p < .05). The within-twin pair analyses revealed the same pattern for the 144 dizygotic twin pairs, but no associations were seen for the 117 monozygotic twin pairs. Accelerometer-measured physical activity and mobility limitations were associated in community-dwelling older adults. Genetic factors may explain some of the variations in physical activity. A personalized exercise program to promote increased physical activity should be provided for older adults who report mobility difficulties. Future research is needed to examine causality between physical activity and mobility limitations.

Connecting loneliness with pathological personality traits: Evidence for genetic and environmental mediation from a study of older twins.

Loneliness has broad public health importance, especially in older adulthood, and there is some evidence suggesting it is associated with several personality disorders (PDs). The etiology of these PD-loneliness associations, however, has rarely been studied, especially in the context of the maladaptive traits of the DSM-5 alternative model of personality disorder (AMPD). To address these limitations, we estimated phenotypic, genetic, and unique environmental associations between loneliness and maladaptive personality traits in a sample of older adults from the Minnesota Twin Registry (n = 1,356, Mage = 70.4). Loneliness was moderately to strongly associated with each of the AMPD domains of negative affect, detachment, antagonism, disinhibition, and psychoticism (r = .22-.58), with evidence of both genetic (rg = .45-.75) and unique environmental (re = .10-.48) influences explaining the associations to varying degrees. We argue that loneliness may be an underappreciated concomitant of personality pathology, with PD traits perhaps underlying its development. Indeed, these findings suggest that loneliness may be a manifestation of the genetic and environmental forces that also lead to pathological personality variation. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

66 The PROMOTe study: prebiotic supplementation improves cognition versus placebo in healthy older twins

Abstract Background There is a growing body of evidence linking the microbiota in the human gut, to the brain and to physical function. Animal and human studies have shown that inducing changes in the microbiota can alter muscle physiology and cognitive behaviour, indicating causative pathways. The PROMOTe trial aimed to test whether the gut microbiome mediates anabolic resistance to protein in older adults. A secondary objective was to test whether modulation of the gut microbiome using a pre-biotic food supplement, improved cognition versus placebo. Methods This placebo-controlled double-blinded randomised controlled trial used twin pairs, recruited from the TwinsUK cohort. Those aged &amp;gt; = 60, with low baseline protein intake, and access to a computer (due to remote trial delivery) were included. One twin received protein supplementation plus placebo and the other received protein supplementation plus a gut microbiome modulator (prebiotic). Intervention period was 12 weeks. Participants were advised to take 1 supplement sachet daily, and to undertake resistance exercises. The primary outcome was muscle strength as measured using chair-rise time. Cognition (CANTAB battery) was a secondary outcome. Linear mixed effects regression models were used to compare intervention groups (arm 1 vs arm 2; blinded). Twin clustering was considered as random effects, both family identifier and zygosity, and treatment group as fixed effect. Results Target sample size was 70 individuals. We screened 626 and randomised 72 participants (36 pairs). More adverse events occurred in the prebiotic group (n = 8 versus n = 2 in placebo group; p = 0.041), but compliance remained high in both groups (% adherence &amp;gt;78% in each group; p = 0.37). There was no significant difference between arms for the primary outcome of chair rise time (coefficient 0.184; 95% CI -0.569-0.938; p = 0.631). The prebiotic intervention arm had an improved cognition factor score versus the placebo group (coefficient 0.482; 95% CI 0.823–0.141; p = 0.014). Conclusion Prebiotic food supplementation improves cognition versus placebo in a cohort of healthy older twins.

Supplemental Material for Connecting Loneliness With Pathological Personality Traits: Evidence for Genetic and Environmental Mediation From a Study of Older Twins

Supplemental Material for Connecting Loneliness With Pathological Personality Traits: Evidence for Genetic and Environmental Mediation From a Study of Older Twins

Genetic, vascular and amyloid components of cerebral blood flow in a preclinical population

Aging-related cognitive decline can be accelerated by a combination of genetic factors, cardiovascular and cerebrovascular dysfunction, and amyloid-β burden. Whereas cerebral blood flow (CBF) has been studied as a potential early biomarker of cognitive decline, its normal variability in healthy elderly is less known. In this study, we investigated the contribution of genetic, vascular, and amyloid-β components of CBF in a cognitively unimpaired (CU) population of monozygotic older twins. We included 134 participants who underwent arterial spin labeling (ASL) MRI and [18F]flutemetamol amyloid-PET imaging at baseline and after a four-year follow-up. Generalized estimating equations were used to investigate the associations of amyloid burden and white matter hyperintensities with CBF. We showed that, in CU individuals, CBF: 1) has a genetic component, as within-pair similarities in CBF values were moderate and significant (ICC > 0.40); 2) is negatively associated with cerebrovascular damage; and 3) is positively associated with the interaction between cardiovascular risk scores and early amyloid-β burden, which may reflect a vascular compensatory response of CBF to early amyloid-β accumulation. These findings encourage future studies to account for multiple interactions with CBF in disease trajectory analyses.

Higher dietary protein intake is associated with sarcopenia in older British twins.

Sarcopenia, characterised by an accelerated loss of skeletal muscle mass and function, is associated with negative outcomes. This study aimed to evaluate factors associated with skeletal muscle strength, mass and sarcopenia, particularly protein intake, and to assess whether shared twin characteristics are important. This study utilised cross-sectional data from a study of community-dwelling twins aged ≥60years. Multivariable logistic regression and between- and within-twin pair regression modelling were used. Participants (n = 3,302) were 89% female (n = 2,923), aged a mean of 72.1 (±7.3) years and composed of 858 (55%) monozygotic, 709 (45%) dizygotic twin pairs and 168 individual lone twins. Using optimal protein intake as the reference group (1.0-1.3g/kg/day), there was no significant association between protein intake (neither high nor low) and low muscle strength, or between low protein intake and sarcopenia (odds ratio (OR) 0.7; 95% confidence interval (CI) 0.39-1.25; P = 0.229) in unadjusted models. High protein intake (>1.3g/kg/day) was associated with low muscle mass (OR 1.76; 95% CI 1.39-2.24; P < 0.0001), while low protein intake was protective (OR 0.52; 95% CI 0.40-0.67; P < 0.0001). High protein intake was associated with sarcopenia (OR 2.04; 95% CI 1.21-3.44; P = 0.008), and this was robust to adjustment for demographic, anthropometric and dietary factors. The association between muscle strength and weight, body mass index, healthy eating index, protein intake and alpha diversity was not significantly influenced by shared twin factors, indicating greater amenability to interventions. High protein intake is associated with sarcopenia in a cohort of healthy older twins.

Traumatic brain injury and dementia risk in male veteran older twins-Controlling for genetic and early life non-genetic factors.

This study leveraged the twin study design, which controls for shared genetic and early life exposures, to investigate the association between traumatic brain injury (TBI) and dementia. Members of the National Academy of Sciences-National Research Council's Twins Registry of World War II male veterans were assigned a cognitive outcome based on a multi-step assessment protocol. History of TBI was obtained via interviews. Among 8302 individuals, risk of non-Alzheimer's disease (non-AD) dementia was higher in those with TBI (hazard ratio [HR]=2.00, 95% confidence interval [CI], 0.97-4.12), than for AD (HR=1.23, 95% CI, 0.76-2.00). To add more control of genetic and shared environmental factors, we analyzed 100 twin pairs discordant for both TBI and dementia onset, and found TBI-associated risk for non-AD dementia increased further (McNemar odds ratio=2.70; 95% CI, 1.27-6.25). These findings suggest that non-AD mechanisms may underlie the association between TBI and dementia, potentially providing insight into inconsistent results from prior studies.

Do Epigenetic Clocks Provide Explanations for Sex Differences in Life Span? A Cross-Sectional Twin Study.

The sex gap in life expectancy has been narrowing in Finland over the past 4-5 decades; however, on average, women still live longer than men. Epigenetic clocks are markers for biological aging which predict life span. In this study, we examined the mediating role of lifestyle factors on the association between sex and biological aging in younger and older adults. Our sample consists of younger and older twins (21‒42 years, n = 1 477; 50‒76 years, n = 763) including 151 complete younger opposite-sex twin pairs (21‒30 years). Blood-based DNA methylation was used to compute epigenetic age acceleration by 4 epigenetic clocks as a measure of biological aging. Path modeling was used to study whether the association between sex and biological aging is mediated through lifestyle-related factors, that is, education, body mass index, smoking, alcohol use, and physical activity. In comparison to women, men were biologically older and, in general, they had unhealthier life habits. The effect of sex on biological aging was partly mediated by body mass index and, in older twins, by smoking. Sex was directly associated with biological aging and the association was stronger in older twins. Previously reported sex differences in life span are also evident in biological aging. Declining smoking prevalence among men is a plausible explanation for the narrowing of the difference in life expectancy between the sexes. Data generated by the epigenetic clocks may help in estimating the effects of lifestyle and environmental factors on aging and in predicting aging in future generations.

Two Sites of r-process Production Assessed on the Basis of the Age-tagged Abundances of Solar Twins

Abstract Solar twins, i.e., stars that are nearly identical to the Sun, including their metallicities, in the solar vicinity show ages widely distributed from 0 to 10 Gyr. This fact matches the orbital history of solar twins in the new paradigm of galactic dynamics, in which stars radially move on the disk when they encounter transient spiral arms. This finding suggests that older twins were born closer to the Galactic center and traveled a longer distance to reach their present location, according to the hypothesis that chemical enrichment occurs more quickly and that solar metallicity is attained on a shorter timescale with a decreasing Galactocentric distance (R GC). We show that abundance patterns covering a wide range of heavy elements for solar twins sharing similar ages are identical and that their variation among different age groups can be understood on the basis of the age–R GC connection within the framework of Galactic chemical evolution. This study identifies the Galactic bulge as the birthplace of the oldest solar twins. Based on this scheme, we find that the relation between [r-process/Fe] and R GC for the inner Galactic region is incompatible with the hypothesis of a sole site for r-process production, that is, neutron star mergers, whose delay time distribution could be approximated by the power-law form (∝ t n ). Alternatively, this relation suggests the presence of two distinct sites for r-process production: short-lived massive stars, ending with specific core-collapse supernovae, and neutron star mergers that are heavily inclined to emerge with longer delay times, as represented by n = 0−0.5.

Determining Zygosity in Infant Twins - Revisiting the Questionnaire Approach.

Accurate zygosity determination is a fundamental step in twin research. Although DNA-based testing is the gold standard for determining zygosity, collecting biological samples is not feasible in all research settings or all families. Previous work has demonstrated the feasibility of zygosity estimation based on questionnaire (physical similarity) data in older twins, but the extent to which this is also a reliable approach in infancy is less well established. Here, we report the accuracy of different questionnaire-based zygosity determination approaches (traditional and machine learning) in 5.5 month-old twins. The participant cohort comprised 284 infant twin pairs (128 dizygotic and 156 monozygotic) who participated in the Babytwins Study Sweden (BATSS). Manual scoring based on an established technique validated in older twins accurately predicted 90.49% of the zygosities with a sensitivity of 91.65% and specificity of 89.06%. The machine learning approach improved the prediction accuracy to 93.10%, with a sensitivity of 91.30% and specificity of 94.29%. Additionally, we quantified the systematic impact of zygosity misclassification on estimates of genetic and environmental influences using simulation-based sensitivity analysis on a separate data set to show the implication of our machine learning accuracy gain. In conclusion, our study demonstrates the feasibility of determining zygosity in very young infant twins using a questionnaire with four items and builds a scalable machine learning model with better metrics, thus a viable alternative to DNA tests in large-scale infant twin studies.

Regional distribution of tau pathology in cognitively unimpaired, genetically identical twins

AbstractBackgroundLimited information is available on the genetic and environmental contributions to early AD pathology. Within a sample of cognitively unimpaired genetically identical older twins we aimed to assess 1) effects of amyloid‐ß pathology on [18F]flortaucipir (tau) binding and 2) spatial similarities in tau patterns within twin pairs.MethodTo date, ten twin pairs (i.e. twenty twins) from the on‐going EMIF‐AD PreclinAD study underwent dynamic (0‐30min and 80‐100min) [18F]flortaucipir PET. Two twin pairs were concordant amyloid‐ß positive, four twin pairs concordant amyloid‐ß negative and four twin pairs amyloid‐ß discordant (i.e. one twin positive and co‐twin negative) based on [18F]flutemetamol visual read. [18F]flortaucipir binding potential (BPND) images were generated using receptor parametric mapping (reference region: cerebellar gray matter). First, we compared [18F]flortaucipir BPND in an early (entorhinal), intermediate (limbic) and late (neocortical) stage tau pathology region between amyloid‐ß positive and negative twins using generalized estimated equation correcting for twin dependency. Next, we examined spatial tau pattern similarities within twin pairs by correlating (Spearman) [18F]flortaucipir BPND across 46 ROIs from the Hammers template between each twin and their co‐twin for each true twin pair. Correlations were also performed for all non‐twin “random” pairs. Correlation coefficients within true twin pairs were compared to the correlation coefficients within random pairs, correcting for age and twin amyloid‐ß status.ResultsAmyloid‐ß positive twins showed higher [18F]flortaucipir BPND in entorhinal (p=0.01) and limbic (p=0.04) regions(Table‐1). Fig‐1 shows representative [18F]flortaucipir images of an amyloid‐ß concordant positive, concordant negative and discordant pair, with regional similarities observed in amyloid‐ß concordant pairs as well as dissimilarities in amyloid‐ß discordant pairs (Fig‐1;Fig‐2). Between‐twin correlations across regional [18F]flortaucipir BPND, to assess spatial tau pattern similarities, were higher for true twin pairs (r=0.71±0.17) compared to random pairs (r=0.45±0.23) (p=0.002)(Table‐2).ConclusionIn line with previous studies, amyloid‐ß positive cognitively unimpaired twins showed higher tau deposition in early and intermediate tau stage regions. Furthermore, we observed higher spatial tau pattern similarities within true twin pairs compared to random pairs, suggesting a moderate genetic contribution to mechanisms underlying tau spread. With the upcoming larger sample we aim to further assess genetic and environmental contributions to early AD pathology.

Potential effects of the shape of gypsum aggregates on the early sulfation of marble and travertine

The damages caused by growth of gypsum crusts on calcareous substrates are well known. Sulfation of stones such as marble and travertine – used in constructions and Cultural Heritage – implies a structural and aesthetical weathering that leads, in time, to flaking, spalling and disruption. The effects of the initial gypsum growth and development were studied by simulating acid attacks on marble and travertine test specimens, evaluating the potential mechanical actions exerted by the shape of the newly grown aggregates. By monitoring the incipient sulfation with optical microscopy and SEM-EDS – backed up by XRPD, a peculiar growth sequence was confirmed: i) at first, tabular ‘Montmartre’ twins grow close and roughly parallel to the calcareous substrate; ii) later, a second generation of prismatic crystals grows on top of the former twins, in aggregates perpendicular to the calcareous matrix. When confined at the grain boundaries or within the narrow pores/fissures typical of marble and travertine textures, these gypsum overgrowths (basal platy twins topped by prismatic crystals) may exert strong crystallization pressures on the host carbonatic matrix, coupled to disjoining pressures granted by persistence of superficial liquid films at the host/guest interface. These phenomena cause the prismatic crystals, shielded by the older twins, to push away the facing calcareous matrix with a repulsive strength that, once the tensile strength is exceeded, brings to flaking, powdering, disruption and spalling. Strictly crystallographic aspects might thus concur to the early deterioration of calcareous substrates after sulfation, favouring mechanical actions that contribute to the damaging effects of gypsum crusts on the surface of buildings and Cultural Heritage in calcareous stones.

Perceived change in physical activity levels and mental health during COVID-19: Findings among adult twin pairs.

Physical distancing and other COVID-19 pandemic mitigation strategies may have unintended consequences on a number of health behaviors and health outcomes. The purpose of this study was to investigate the association between perceived change in physical activity or exercise and mental health outcomes over the short-term in response to COVID-19 mitigation strategies in a sample of adult twins. This was a cross-sectional study of 3,971 identical and same-sex fraternal adult twins (909 pairs, 77% identical) from the community-based Washington State Twin Registry. Participants in this study completed an online survey examining the impact of COVID-19 mitigation on a number of health-related behaviors and outcomes, administered between March 26 and April 5, 2020. In the present study, the exposure was perceived change in physical activity or exercise. The outcomes were levels of perceived anxiety and stress. More twin pairs reported a decrease in physical activity levels (42%) than those reporting no change (31%) or increased physical activity levels (27%). A perceived decrease in physical activity or exercise was associated with higher stress and anxiety levels. However, the physical activity-stress relationship was confounded by genetic and shared environmental factors. On the other hand, the physical activity-anxiety relationship held after controlling for genetic and shared environmental factors, although it was no longer significant after further controlling for age and sex, with older twins more likely to report lower levels of anxiety and females more likely to report higher levels of anxiety. Strategies to mitigate the COVID-19 pandemic may be impacting physical activity and mental health, with those experiencing a decrease in physical activity also having higher levels of stress and anxiety. These relationships are confounded by genetic and shared environmental factors, in the case of stress, and age and sex, in the case of anxiety.

Motives for physical activity in older men and women: A twin study using accelerometer-measured physical activity.

Motives for physical activity may vary considerably by age, sex, and the level of physical activity. We aimed to examine motives for physical activity in older men and women with different physical activity levels as well as whether genetic and/or environmental factors explain those motives. Finnish twins (mean age 72.9years, 262 full twin pairs) self-reported their motives for physical activity. Time spent on moderate-to-vigorous physical activity was monitored using a hip-worn accelerometer. Comparisons between the different physical activity groups of older twins (n=764-791/motive dimension) were analyzed using the Wald test, and effect sizes were calculated as Cohen's d. Quantitative genetic modeling was used to estimate genetic and environmental contributions. For both sexes, the most frequently reported motives for physical activity were physical fitness, health maintenance, and psychological well-being. Conforming to others' expectations was more important for men than for women (P<.001, Cohen's d=0.38), while appearance (P=.001 Cohen's d=-0.24) and psychological well-being (P=.02, Cohen's d=-0.17) were highlighted by women. Most of the motive dimensions differed significantly between the physically active and inactive individuals. It was estimated that 5%-42% of the variation in motives was contributed by genetic factors and 58%-95% by environmental factors. The result that environmental factors contribute in a great deal to motives indicates that interventions to motivate physically inactive older individuals to be physically active can be successful. However, personalized interventions are needed because sex and the level of physical activity were found to be associated with older individuals' motives for physical activity.

Replicating associations between DNA methylation and body mass index in a longitudinal sample of older twins.

There is an important interplay between epigenetic factors and body weight, and previous work has identified ten sites where DNA methylation is robustly associated with body mass index (BMI) cross-sectionally. However, interpretation of the associations is complicated by the substantial changes in BMI often occurring in late-life, and the fact that methylation is often driven by genetic variation. This study therefore investigated the longitudinal association between these ten sites and BMI from midlife to late-life, and whether associations persist after controlling for genetic factors. We used data from 535 individuals (mean age 68) in the Swedish Adoption/Twin Study of Aging (SATSA) with longitudinal measures of both DNA methylation from blood samples and BMI, spanning up to 20 years. Methylation levels were measured with the Infinium Human Methylation 450K or Infinium MethylationEpic array, with seven of the ten sites passing quality control. Latent growth curve models were applied to investigate longitudinal associations between methylation and BMI, and between-within models to study associations within twin pairs, thus adjusting for genetic factors. Baseline DNA methylation levels at five of the seven sites were associated with BMI level at age 65 (cg00574958 [CPT1A]; cg11024682 [SREBF1]), and/or change (cg06192883 [MYO5C]; cg06946797 [RMI2]; cg08857797 [VPS25]). For four of the five sites, the associations remained comparable within twin pairs. However, the effects of cg06192883 were substantially attenuated within pairs. No change in DNA methylation was detected for any of the seven evaluated sites. Five of the seven sites investigated were associated with late-life level and/or change in BMI. The effects for four of the sites remained similar when examined within twin pairs, indicating that the associations are mainly environmentally driven. However, the substantial attenuation in the association between cg06192883 and late-life BMI within pairs points to the importance of genetic factors in this association.

Update on Osaka University Twin Registry: An Overview of Multidisciplinary Research Resources and Biobank at Osaka University Center for Twin Research

The Osaka University Twin Registry was originally established as a registry of older twins but was subsequently expanded to include twins of all ages. The Center for Twin Research at Osaka University Graduate School of Medicine has been managing this registry, as well as collecting research information and bioresources from twin participants. Based on the resources, multidisciplinary research projects have been conducted in collaboration with researchers from institutions both inside and outside Japan. One of the main aims of the center is to collect research information as well as biological resources from registered twins, and to establish a biobank and databases of these data and bioresources. Although data availability may vary, the following data have been collected: physical data (e.g., height, body weight, blood pressure, theoretical visceral fat, pulse wave velocity and bone density); epidemiological data (e.g., medical history, lifestyle, quality of life, mood status, cognitive function and nutritional status); electrocardiography, ultrasonography (carotid artery and thyroid); dentistry, dermatological assessment; positron emission tomography; magnetoencephalographam; brain magnetic resonance imaging (MRI); and functional MRI. In addition to these in-person survey data, microbiome data have been collected from some participants. As for bioresources, peripheral blood is obtained from the participants for isolation of serum and extraction of DNA and RNA, then stored in deep freezers for further analyses. A variety of research projects are in progress and more are on the way both in Japan and internationally using these data.

The Older Finnish Twin Cohort - 45 Years of Follow-up.

The older Finnish Twin Cohort (FTC) was established in 1974. The baseline survey was in 1975, with two follow-up health surveys in 1981 and 1990. The fourth wave of assessments was done in three parts, with a questionnaire study of twins born during 1945-1957 in 2011-2012, while older twins were interviewed and screened for dementia in two time periods, between 1999 and 2007 for twins born before 1938 and between 2013 and 2017 for twins born in 1938-1944. The content of these wave 4 assessments is described and some initial results are described. In addition, we have invited twin-pairs, based on response to the cohortwide surveys, to participate in detailed in-person studies; these are described briefly together with key results. We also review other projects based on the older FTC and provide information on the biobanking of biosamples and related phenotypes.

Cerebral Blood Flow in Community-Based Older Twins Is Moderately Heritable: An Arterial Spin Labeling Perfusion Imaging Study.

Adequate cerebral blood flow (CBF) is necessary to maintain brain metabolism and function. Arterial spin labeling (ASL) is an emerging MRI technique offering a non-invasive and reliable quantification of CBF. The genetic basis of CBF has not been well documented, and one approach to investigate this is to examine its heritability. The current study aimed to examine the heritability of CBF using ASL data from a cohort of community-dwelling older twins (41 monozygotic (MZ) and 25 dizygotic (DZ) twin pairs; age range, 65–93 years; 56.4% female). The results showed that the cortex had higher CBF than subcortical gray matter (GM) regions, and CBF in the GM regions of the anterior cerebral artery (ACA) territory was lower than that of the middle (MCA) and posterior (PCA) cerebral arteries. After accounting for the effects of age, sex and scanner, moderate heritability was identified for global CBF (h2 = 0.611; 95% CI = 0.380–0.761), as well as for cortical and subcortical GM and the GM in the major arterial territories (h2 = 0.500–0.612). Strong genetic correlations (GCs) were found between CBF in subcortical and cortical GM regions, as well as among the three arterial territories (ACA, MCA, PCA), suggesting a largely convergent genetic control for the CBF in brain GM. The moderate heritability of CBF warrants future investigations to uncover the genetic variants and genes that regulate CBF.

Heritability of the Number of Teeth in Middle-Aged and Older Danish Twins

Tooth loss is a common health concern in older adults. We aimed to estimate the relative contributions of genetic and environmental factors to the variation in the number of teeth in middle-aged and older populations using a population-based cohort of Danish twins. The study included 5,269 Danish middle-aged or older twins who provided data on the number of teeth at baseline by structured interviews. The data were analyzed using univariate liability threshold modeling, stratified by sex and age, to estimate familial risk of tooth loss as well as estimates of heritability. In the whole cohorts, 23% of participants were edentate and 53% had retained 20 or more teeth. A statistical model including additive genetic factors and environmental factors partly shared by co-twins and partly unique to each individual twin gave the best statistical fit for the number of teeth in both age categories as well as in men and women. Overall, additive genetic factors explained 36% (95% confidence interval [CI]: 23% to 49%), common environmental factors 20% (95% CI: 9% to 31%), and unique environmental factors 44% (95% CI: 40% to 48%) of the total variation of the number of teeth. This study indicates that a substantial part of the variation in tooth loss is explained by genetic as well as environmental factors shared by co-twins. Our results implied that family background importantly affects tooth loss in both the middle-aged and the older populations. Family history is thus an important factor to take into account in dental health care.