ORCID Profile
0000-0002-8987-1755
Current Organisation
University of California, San Diego
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Publisher: Cold Spring Harbor Laboratory
Date: 03-11-2020
DOI: 10.1101/2020.11.02.362780
Abstract: Both cognitive reserve and modifiable lifestyle behaviors are associated with dementia risk. The effect of early lifestyle behaviors and cognitive reserve on late midlife brain aging could inform early identification and risk reduction of future dementia. Determine associations of young adult cognitive reserve, early midlife lifestyle behaviors, and the reserve-by-lifestyle interaction on late midlife brain age. Examine the relationship between mild cognitive impairment (MCI) and brain age. Participants were from the nationally representative Vietnam Era Twin Study of Aging (VETSA). Cognitive reserve was assessed at median age 20 years (IQR=1.38) with the Armed Forces Qualification Test (AFQT). Lifestyle behaviors (smoking, alcohol consumption, and social engagement) were assessed at median age 41 (IQR=5.00). Structural brain imaging conducted at median age 69 (IQR=4.74) was used to construct predicted brain age difference scores (PBAD=chronological age minus predicted brain age) and MCI was ascertained. In-person cognitive testing (ages 20 and 69) mailed survey (age 41) structural MRI, MCI diagnosis at University of California, San Diego (age 69). 431 community-dwelling men. AFQT self-reported health and lifestyle behaviors. PBAD scores MCI. In fully adjusted mixed linear models, age 20 cognitive reserve and the age 41 lifestyle composite were associated with age 69 PBAD [t (104)=2.62, p=0.01, 95%CI 0.874, 6.285 t (104)=3.37, p=0.001, 95%CI 0.583, 2.249 respectively] as was the reserve-by-lifestyle interaction [t (104) = −2.29, p=0.02, 95%CI −2.330, −0.167]. Unfavorable lifestyle predicted more advanced brain age, but only for those with lower young adult cognitive reserve. The MCI group had more advanced brain age (F (2,130) = 3.13 p=0.05). Favorable lifestyle behaviors promoted resistance to accelerated brain aging 3 decades later for those with lower young adult cognitive reserve. High reserve appeared to be protective regardless of lifestyle. The association with MCI suggests that advanced PBAD scores reflect poorer brain integrity, although it is unclear if PBAD is related to Alzheimer’s dementia specifically. Lower cognitive reserve increases risk for dementia, but early lifestyle modification may promote healthier brain aging and dementia risk reduction, particularly in those with lower reserve. Cohort Study Do modifiable lifestyle behaviors in early midlife predict later accelerated brain aging and is that association moderated by cognitive reserve? A lifestyle composite of smoking, alcohol consumption and social engagement at age 41 was associated with estimated brain age in late midlife. There was a significant moderation effect whereby more unfavorable lifestyle behaviors predicted more advanced brain aging, but only in those with low-to-moderate cognitive reserve. Favorable lifestyle behaviors appear to be protective for brain integrity especially among those with lower cognitive reserve. Early midlife efforts at prevention could be prioritized among those with lower cognitive reserve.
Publisher: Springer Science and Business Media LLC
Date: 22-09-2020
DOI: 10.1038/S41467-020-18367-Y
Abstract: Cortical thickness, surface area and volumes vary with age and cognitive function, and in neurological and psychiatric diseases. Here we report heritability, genetic correlations and genome-wide associations of these cortical measures across the whole cortex, and in 34 anatomically predefined regions. Our discovery s le comprises 22,824 in iduals from 20 cohorts within the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) consortium and the UK Biobank. We identify genetic heterogeneity between cortical measures and brain regions, and 160 genome-wide significant associations pointing to wnt/β-catenin, TGF-β and sonic hedgehog pathways. There is enrichment for genes involved in anthropometric traits, hindbrain development, vascular and neurodegenerative disease and psychiatric conditions. These data are a rich resource for studies of the biological mechanisms behind cortical development and aging.
Publisher: Cambridge University Press (CUP)
Date: 10-2017
DOI: 10.1017/THG.2017.49
Abstract: Whether monozygotic (MZ) and dizygotic (DZ) twins differ from each other in a variety of phenotypes is important for genetic twin modeling and for inferences made from twin studies in general. We analyzed whether there were differences in in idual, maternal and paternal education between MZ and DZ twins in a large pooled dataset. Information was gathered on in idual education for 218,362 adult twins from 27 twin cohorts (53% females 39% MZ twins), and on maternal and paternal education for 147,315 and 143,056 twins respectively, from 28 twin cohorts (52% females 38% MZ twins). Together, we had information on in idual or parental education from 42 twin cohorts representing 19 countries. The original education classifications were transformed to education years and analyzed using linear regression models. Overall, MZ males had 0.26 (95% CI [0.21, 0.31]) years and MZ females 0.17 (95% CI [0.12, 0.21]) years longer education than DZ twins. The zygosity difference became smaller in more recent birth cohorts for both males and females. Parental education was somewhat longer for fathers of DZ twins in cohorts born in 1990–1999 (0.16 years, 95% CI [0.08, 0.25]) and 2000 or later (0.11 years, 95% CI [0.00, 0.22]), compared with fathers of MZ twins. The results show that the years of both in idual and parental education are largely similar in MZ and DZ twins. We suggest that the socio-economic differences between MZ and DZ twins are so small that inferences based upon genetic modeling of twin data are not affected.
Publisher: Cambridge University Press (CUP)
Date: 04-09-2015
DOI: 10.1017/THG.2015.57
Abstract: A trend toward greater body size in dizygotic (DZ) than in monozygotic (MZ) twins has been suggested by some but not all studies, and this difference may also vary by age. We analyzed zygosity differences in mean values and variances of height and body mass index (BMI) among male and female twins from infancy to old age. Data were derived from an international database of 54 twin cohorts participating in the COllaborative project of Development of Anthropometrical measures in Twins (CODATwins), and included 842,951 height and BMI measurements from twins aged 1 to 102 years. The results showed that DZ twins were consistently taller than MZ twins, with differences of up to 2.0 cm in childhood and adolescence and up to 0.9 cm in adulthood. Similarly, a greater mean BMI of up to 0.3 kg/m 2 in childhood and adolescence and up to 0.2 kg/m 2 in adulthood was observed in DZ twins, although the pattern was less consistent. DZ twins presented up to 1.7% greater height and 1.9% greater BMI than MZ twins these percentage differences were largest in middle and late childhood and decreased with age in both sexes. The variance of height was similar in MZ and DZ twins at most ages. In contrast, the variance of BMI was significantly higher in DZ than in MZ twins, particularly in childhood. In conclusion, DZ twins were generally taller and had greater BMI than MZ twins, but the differences decreased with age in both sexes.
Publisher: Elsevier BV
Date: 2022
Publisher: Oxford University Press (OUP)
Date: 2018
Abstract: Childhood socioeconomic status (cSES) is found to predict later-life cognitive abilities, yet the mechanisms underlying these associations remain unclear. The objective of this longitudinal study was to examine the direct and indirect paths through which cSES influences late midlife cognitive outcomes. Participants were 1,009 male twins in the Vietnam Era Twin Study of Aging (VETSA). At mean ages 20 and 62, participants completed a standardized test for general cognitive ability (GCA). The age 62 cognitive assessment also included in-person tests of processing speed, episodic memory, abstract reasoning, working memory, verbal fluency, visual-spatial ability, and executive functions. At mean age 56, participants were interviewed regarding their own and their parents’ education and occupation, and completed questionnaires about cognitive leisure activities and sociodemographic information. Multiple mediation analyses were conducted to examine the direct path effects and indirect path effects of cSES through age 20 GCA, adult SES, and cognitive leisure activities on seven cognitive outcomes at age 62, adjusting for age, ethnicity, and non-independence of observations. Total (direct plus indirect) effects were significant for all measures with the exception of executive functions. Men from lower cSES backgrounds had poorer cognitive functioning in late midlife. The direct effect of cSES was partially mediated for abstract reasoning, and was fully mediated for the remaining six cognitive outcomes. Total indirect effects accounted for at least half of the total effects in each model, with paths through age 20 GCA explaining most of the total indirect effects. cSES predicted cognitive functioning in late middle age Using multiple mediation models, we show that lower cSES predicts poorer cognition in late midlife primarily through young adult cognitive ability and to a lesser extent through SES in adulthood and engagement in cognitively stimulating activities.
Publisher: Cambridge University Press (CUP)
Date: 27-05-2015
DOI: 10.1017/THG.2015.29
Abstract: For over 100 years, the genetics of human anthropometric traits has attracted scientific interest. In particular, height and body mass index (BMI, calculated as kg/m 2 ) have been under intensive genetic research. However, it is still largely unknown whether and how heritability estimates vary between human populations. Opportunities to address this question have increased recently because of the establishment of many new twin cohorts and the increasing accumulation of data in established twin cohorts. We started a new research project to analyze systematically (1) the variation of heritability estimates of height, BMI and their trajectories over the life course between birth cohorts, ethnicities and countries, and (2) to study the effects of birth-related factors, education and smoking on these anthropometric traits and whether these effects vary between twin cohorts. We identified 67 twin projects, including both monozygotic (MZ) and dizygotic (DZ) twins, using various sources. We asked for in idual level data on height and weight including repeated measurements, birth related traits, background variables, education and smoking. By the end of 2014, 48 projects participated. Together, we have 893,458 height and weight measures (52% females) from 434,723 twin in iduals, including 201,192 complete twin pairs (40% monozygotic, 40% same-sex dizygotic and 20% opposite-sex dizygotic) representing 22 countries. This project demonstrates that large-scale international twin studies are feasible and can promote the use of existing data for novel research purposes.
Publisher: Public Library of Science (PLoS)
Date: 12-07-2018
Publisher: eLife Sciences Publications, Ltd
Date: 14-12-2016
DOI: 10.7554/ELIFE.20320
Abstract: Human height variation is determined by genetic and environmental factors, but it remains unclear whether their influences differ across birth-year cohorts. We conducted an in idual-based pooled analysis of 40 twin cohorts including 143,390 complete twin pairs born 1886–1994. Although genetic variance showed a generally increasing trend across the birth-year cohorts, heritability estimates (0.69-0.84 in men and 0.53-0.78 in women) did not present any clear pattern of secular changes. Comparing geographic-cultural regions (Europe, North America and Australia, and East Asia), total height variance was greatest in North America and Australia and lowest in East Asia, but no clear pattern in the heritability estimates across the birth-year cohorts emerged. Our findings do not support the hypothesis that heritability of height is lower in populations with low living standards than in affluent populations, nor that heritability of height will increase within a population as living standards improve.
Publisher: Springer Science and Business Media LLC
Date: 04-03-2019
Publisher: Cold Spring Harbor Laboratory
Date: 19-01-2023
DOI: 10.1101/2023.01.16.524331
Abstract: Investigators in neuroscience have turned to Big Data to address replication and reliability issues by increasing s le sizes, statistical power, and representativeness of data. These efforts unveil new questions about integrating data arising from distinct sources and instruments. We focus on the most frequently assessed cognitive domain - memory testing - and demonstrate a process for reliable data harmonization across three common measures. We aggregated global raw data from 53 studies totaling N = 10,505 in iduals. A mega-analysis was conducted using empirical bayes harmonization to remove site effects, followed by linear models adjusting for common covariates. A continuous item response theory (IRT) model estimated each in idual’s latent verbal learning ability while accounting for item difficulties. Harmonization significantly reduced inter-site variance while preserving covariate effects, and our conversion tool is freely available online. This demonstrates that large-scale data sharing and harmonization initiatives can address reproducibility and integration challenges across the behavioral sciences. We present a global effort to devise harmonization procedures necessary to meaningfully leverage big data.
Publisher: Wiley
Date: 29-12-2016
DOI: 10.1002/HBM.23502
Publisher: Springer Science and Business Media LLC
Date: 08-04-2022
DOI: 10.1038/S42003-022-03287-Y
Abstract: Circulating total-tau levels can be used as an endophenotype to identify genetic risk factors for tauopathies and related neurological disorders. Here, we confirmed and better characterized the association of the 17q21 MAPT locus with circulating total-tau in 14,721 European participants and identified three novel loci in 953 African American participants (4q31, 5p13, and 6q25) at P 5 × 10 −8 . We additionally detected 14 novel loci at P 5 × 10 −7 , specific to either Europeans or African Americans. Using whole-exome sequence data in 2,279 European participants, we identified ten genes associated with circulating total-tau when aggregating rare variants. Our genetic study sheds light on genes reported to be associated with neurological diseases including stroke, Alzheimer’s, and Parkinson’s ( F 5, MAP1B , and BCAS3 ), with Alzheimer’s pathological hallmarks ( ADAMTS12 , IL15 , and FHIT ), or with an important function in the brain ( PARD3 , ELFN2 , UBASH3B , SLIT3 , and NSD3 ), and suggests that the genetic architecture of circulating total-tau may differ according to ancestry.
Publisher: Elsevier BV
Date: 12-2021
Publisher: Cold Spring Harbor Laboratory
Date: 17-10-2022
DOI: 10.1101/2022.10.13.512111
Abstract: The cerebellum critically contributes to higher-order cognitive and emotional functions such fear learning and memory. Prior research on cerebellar volume in PTSD is scant and has neglected neuroanatomical sub isions of the cerebellum that differentially map on to motor, cognitive, and affective functions. We quantified cerebellar lobule volumes using structural magnetic resonance imaging in 4,215 adults (PTSD n= 1640 Control n=2575) across 40 sites from the from the ENIGMA-PGC PTSD working group. Using a new state-of-the-art deep-learning based approach for automatic cerebellar parcellation, we obtained volumetric estimates for the total cerebellum and 28 subregions. Linear mixed effects models controlling for age, gender, intracranial volume, and site were used to compare cerebellum total and subregional volume in PTSD compared to healthy controls. The Benjamini-Hochberg procedure was used to control the false discovery rate ( p -FDR .05). PTSD was associated with significant grey and white matter reductions of the cerebellum. Compared to controls, people with PTSD demonstrated smaller total cerebellum volume. In addition, people with PTSD showed reduced volume in subregions primarily within the posterior lobe (lobule VIIB, crus II), but also the vermis (VI, VIII), flocculonodular lobe (lobule X), and cerebellar white matter (all p -FDR 0.05). Effects of PTSD on volume were consistent, and generally more robust, when examining symptom severity rather than diagnostic status. These findings implicate regionally specific cerebellar volumetric differences in the pathophysiology of PTSD. The cerebellum appears to play an important role in high-order cognitive and emotional processes, far beyond its historical association with vestibulomotor function. Further examination of the cerebellum in trauma-related psychopathology will help to clarify how cerebellar structure and function may disrupt cognitive and affective processes at the center of translational models for PTSD.
Publisher: Cold Spring Harbor Laboratory
Date: 10-06-2021
DOI: 10.1101/2021.06.08.447489
Abstract: Over the past few decades, neuroimaging has become a ubiquitous tool in basic research and clinical studies of the human brain. However, no reference standards currently exist to quantify in idual differences in neuroimaging metrics over time, in contrast to growth charts for anthropometric traits such as height and weight 1 . Here, we built an interactive resource to benchmark brain morphology, www.brainchart.io , derived from any current or future s le of magnetic resonance imaging (MRI) data. With the goal of basing these reference charts on the largest and most inclusive dataset available, we aggregated 123,984 MRI scans from 101,457 participants aged from 115 days post-conception through 100 postnatal years, across more than 100 primary research studies. Cerebrum tissue volumes and other global or regional MRI metrics were quantified by centile scores, relative to non-linear trajectories 2 of brain structural changes, and rates of change, over the lifespan. Brain charts identified previously unreported neurodevelopmental milestones 3 showed high stability of in idual centile scores over longitudinal assessments and demonstrated robustness to technical and methodological differences between primary studies. Centile scores showed increased heritability compared to non-centiled MRI phenotypes, and provided a standardised measure of atypical brain structure that revealed patterns of neuroanatomical variation across neurological and psychiatric disorders. In sum, brain charts are an essential first step towards robust quantification of in idual deviations from normative trajectories in multiple, commonly-used neuroimaging phenotypes. Our collaborative study proves the principle that brain charts are achievable on a global scale over the entire lifespan, and applicable to analysis of erse developmental and clinical effects on human brain structure. Furthermore, we provide open resources to support future advances towards adoption of brain charts as standards for quantitative benchmarking of typical or atypical brain MRI scans.
Publisher: Cold Spring Harbor Laboratory
Date: 06-08-2021
DOI: 10.1101/2021.08.04.455143
Abstract: Despite their increasing application, the genetic and environmental etiology of global predicted brain ageing (PBA) indices is unknown. Likewise, the degree to which genetic influences in PBA are longitudinally stable and how PBA changes over time are also unknown. We analyzed data from 734 men from the Vietnam Era Twin Study of Aging with repeated MRI assessments between the ages 52 to 72 years. Biometrical genetic analyses revealed significant and highly correlated estimates of additive genetic heritability ranging from 59% to 75%. Multivariate longitudinal modelling revealed that covariation between PBA at different timepoints could be explained by a single latent factor with 73% heritability. Our results suggest that genetic influences on PBA are detectable in midlife or earlier, are longitudinally very stable, and are largely explained by common genetic influences.
Publisher: Elsevier BV
Date: 07-2019
Publisher: Wiley
Date: 05-06-2017
DOI: 10.1002/HBM.23672
Publisher: Wiley
Date: 09-02-2018
DOI: 10.1002/HBM.24002
Location: United States of America
Location: United States of America
No related grants have been discovered for Carol Franz.