ORCID Profile
0000-0001-5599-6237
Current Organisations
The University of Texas at Austin
,
The Texas Twin Project
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Publisher: Cambridge University Press (CUP)
Date: 31-07-2019
DOI: 10.1017/THG.2019.35
Abstract: The COllaborative project of Development of Anthropometrical measures in Twins (CODATwins) project is a large international collaborative effort to analyze in idual-level phenotype data from twins in multiple cohorts from different environments. The main objective is to study factors that modify genetic and environmental variation of height, body mass index (BMI, kg/m 2 ) and size at birth, and additionally to address other research questions such as long-term consequences of birth size. The project started in 2013 and is open to all twin projects in the world having height and weight measures on twins with information on zygosity. Thus far, 54 twin projects from 24 countries have provided in idual-level data. The CODATwins database includes 489,981 twin in iduals (228,635 complete twin pairs). Since many twin cohorts have collected longitudinal data, there is a total of 1,049,785 height and weight observations. For many cohorts, we also have information on birth weight and length, own smoking behavior and own or parental education. We found that the heritability estimates of height and BMI systematically changed from infancy to old age. Remarkably, only minor differences in the heritability estimates were found across cultural–geographic regions, measurement time and birth cohort for height and BMI. In addition to genetic epidemiological studies, we looked at associations of height and BMI with education, birth weight and smoking status. Within-family analyses examined differences within same-sex and opposite-sex dizygotic twins in birth size and later development. The CODATwins project demonstrates the feasibility and value of international collaboration to address gene-by-exposure interactions that require large s le sizes and address the effects of different exposures across time, geographical regions and socioeconomic status.
Publisher: Springer Science and Business Media LLC
Date: 18-07-2019
DOI: 10.1038/S41467-019-11177-X
Abstract: Although plasma proteins may serve as markers of neurological disease risk, the molecular mechanisms responsible for inter-in idual variation in plasma protein levels are poorly understood. Therefore, we conduct genome- and epigenome-wide association studies on the levels of 92 neurological proteins to identify genetic and epigenetic loci associated with their plasma concentrations (n = 750 healthy older adults). We identify 41 independent genome-wide significant (P 5.4 × 10 −10 ) loci for 33 proteins and 26 epigenome-wide significant (P 3.9 × 10 −10 ) sites associated with the levels of 9 proteins. Using this information, we identify biological pathways in which putative neurological biomarkers are implicated (neurological, immunological and extracellular matrix metabolic pathways). We also observe causal relationships (by Mendelian randomisation analysis) between changes in gene expression (DRAXIN, MDGA1 and KYNU), or DNA methylation profiles (MATN3, MDGA1 and NEP), and altered plasma protein levels. Together, this may help inform causal relationships between biomarkers and neurological diseases.
Publisher: Springer Science and Business Media LLC
Date: 05-2022
DOI: 10.1038/S41588-022-01062-7
Abstract: Estimates from genome-wide association studies (GWAS) of unrelated in iduals capture effects of inherited variation (direct effects), demography (population stratification, assortative mating) and relatives (indirect genetic effects). Family-based GWAS designs can control for demographic and indirect genetic effects, but large-scale family datasets have been lacking. We combined data from 178,086 siblings from 19 cohorts to generate population (between-family) and within-sibship (within-family) GWAS estimates for 25 phenotypes. Within-sibship GWAS estimates were smaller than population estimates for height, educational attainment, age at first birth, number of children, cognitive ability, depressive symptoms and smoking. Some differences were observed in downstream SNP heritability, genetic correlations and Mendelian randomization analyses. For ex le, the within-sibship genetic correlation between educational attainment and body mass index attenuated towards zero. In contrast, analyses of most molecular phenotypes (for ex le, low-density lipoprotein-cholesterol) were generally consistent. We also found within-sibship evidence of polygenic adaptation on taller height. Here, we illustrate the importance of family-based GWAS data for phenotypes influenced by demographic and indirect genetic effects.
Publisher: eLife Sciences Publications, Ltd
Date: 13-01-2022
DOI: 10.7554/ELIFE.71802
Abstract: Protein biomarkers have been identified across many age-related morbidities. However, characterising epigenetic influences could further inform disease predictions. Here, we leverage epigenome-wide data to study links between the DNA methylation (DNAm) signatures of the circulating proteome and incident diseases. Using data from four cohorts, we trained and tested epigenetic scores (EpiScores) for 953 plasma proteins, identifying 109 scores that explained between 1% and 58% of the variance in protein levels after adjusting for known protein quantitative trait loci (pQTL) genetic effects. By projecting these EpiScores into an independent s le (Generation Scotland n = 9537) and relating them to incident morbidities over a follow-up of 14 years, we uncovered 137 EpiScore-disease associations. These associations were largely independent of immune cell proportions, common lifestyle and health factors, and biological aging. Notably, we found that our diabetes-associated EpiScores highlighted previous top biomarker associations from proteome-wide assessments of diabetes. These EpiScores for protein levels can therefore be a valuable resource for disease prediction and risk stratification.
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: 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: Springer Science and Business Media LLC
Date: 17-06-2021
Publisher: Elsevier BV
Date: 12-2019
Publisher: Cold Spring Harbor Laboratory
Date: 10-05-2021
DOI: 10.1101/2021.05.06.21256747
Abstract: Genome-wide association studies (GWAS) of proxy-phenotypes using family history of disease (GWAX) substantially boost power for genetic discovery when combined with direct case-control GWAS, most prominently in the context of Alzheimer’s Disease (AD). However, despite twin study heritability estimates of approximately 60%, recent SNP-based estimates of common variant heritability of AD from meta-analyzed GWAS-GWAX data have been particularly low (2.5%), calling into question the prospects of continued progress in AD genetics. We demonstrate that commonly used approaches for combining GWAX and GWAS data produce dramatic underestimates of heritability, and we introduce a multivariate method for estimating in idual SNP effects and recovering unbiased estimates of SNP heritability when combining GWAS and GWAX summary data. We estimate the SNP heritability of Clinical AD diagnoses excluding the APOE region at ∼6-10%, with the corresponding estimate for biological AD (based on prevalence rate estimates from recently published molecular imaging data) as high as ∼20%. Common variant risk for AD appears to represent a very strong effect of APOE superimposed upon a relatively diffuse polygenic signal that is distributed across the genome.
Publisher: Informa UK Limited
Date: 25-06-2018
Publisher: Springer Science and Business Media LLC
Date: 23-06-2016
DOI: 10.1038/SREP28496
Abstract: Height variation is known to be determined by both genetic and environmental factors, but a systematic description of how their influences differ by sex, age and global regions is lacking. We conducted an in idual-based pooled analysis of 45 twin cohorts from 20 countries, including 180,520 paired measurements at ages 1–19 years. The proportion of height variation explained by shared environmental factors was greatest in early childhood, but these effects remained present until early adulthood. Accordingly, the relative genetic contribution increased with age and was greatest in adolescence (up to 0.83 in boys and 0.76 in girls). Comparing geographic-cultural regions (Europe, North-America and Australia and East-Asia), genetic variance was greatest in North-America and Australia and lowest in East-Asia, but the relative proportion of genetic variation was roughly similar across these regions. Our findings provide further insights into height variation during childhood and adolescence in populations representing different ethnicities and exposed to different environments.
Publisher: Elsevier BV
Date: 08-2016
Publisher: Springer Science and Business Media LLC
Date: 14-07-2020
DOI: 10.1038/S41467-020-17117-4
Abstract: Estimates from Mendelian randomization studies of unrelated in iduals can be biased due to uncontrolled confounding from familial effects. Here we describe methods for within-family Mendelian randomization analyses and use simulation studies to show that family-based analyses can reduce such biases. We illustrate empirically how familial effects can affect estimates using data from 61,008 siblings from the Nord-Trøndelag Health Study and UK Biobank and replicated our findings using 222,368 siblings from 23andMe. Both Mendelian randomization estimates using unrelated in iduals and within family methods reproduced established effects of lower BMI reducing risk of diabetes and high blood pressure. However, while Mendelian randomization estimates from s les of unrelated in iduals suggested that taller height and lower BMI increase educational attainment, these effects were strongly attenuated in within-family Mendelian randomization analyses. Our findings indicate the necessity of controlling for population structure and familial effects in Mendelian randomization studies.
Publisher: Wiley
Date: 25-01-2022
DOI: 10.1111/DESC.13228
Abstract: Self‐regulation is a widely studied construct, generally assumed to be cognitively supported by executive functions (EFs). There is a lack of clarity and consensus over the roles of specific components of EFs in self‐regulation. The current study examines the relations between performance on (a) a self‐regulation task (Heads, Toes, Knees Shoulders Task) and (b) two EF tasks (Knox Cube and Beads Tasks) that measure different components of updating: working memory and short‐term memory, respectively. We compared 107 8‐ to 13‐year‐old children (64 females) across demographically‐ erse populations in four low and middle‐income countries, including: Tanna, Vanuatu Keningau, Malaysia Saltpond, Ghana and Natal, Brazil. The communities we studied vary in market integration/urbanicity as well as level of access, structure, and quality of schooling. We found that performance on the visuospatial working memory task (Knox Cube) and the visuospatial short‐term memory task (Beads) are each independently associated with performance on the self‐regulation task, even when controlling for schooling and location effects. These effects were robust across demographically‐ erse populations of children in low‐and middle‐income countries. We conclude that this study found evidence supporting visuospatial working memory and visuospatial short‐term memory as distinct cognitive processes which each support the development of self‐regulation.
Publisher: Cold Spring Harbor Laboratory
Date: 09-04-2019
DOI: 10.1101/602516
Abstract: Mendelian randomization (MR) is a widely-used method for causal inference using genetic data. Mendelian randomization studies of unrelated in iduals may be susceptible to bias from family structure, for ex le, through dynastic effects which occur when parental genotypes directly affect offspring phenotypes. Here we describe methods for within-family Mendelian randomization and through simulations show that family-based methods can overcome bias due to dynastic effects. We illustrate these issues empirically using data from 61,008 siblings from the UK Biobank and Nord-Trøndelag Health Study. Both within-family and population-based Mendelian randomization analyses reproduced established effects of lower BMI reducing risk of diabetes and high blood pressure. However, while MR estimates from population-based s les of unrelated in iduals suggested that taller height and lower BMI increase educational attainment, these effects largely disappeared in within-family MR analyses. We found differences between population-based and within-family based estimates, indicating the importance of controlling for family effects and population structure in Mendelian randomization studies.
Publisher: Springer Science and Business Media LLC
Date: 2021
Publisher: Springer Science and Business Media LLC
Date: 08-07-2020
Publisher: Cold Spring Harbor Laboratory
Date: 02-12-2020
DOI: 10.1101/2020.12.01.404681
Abstract: Protein biomarkers have been identified across many age-related morbidities. However, characterising epigenetic influences could further inform disease predictions. Here, we leverage epigenome-wide data to study links between the DNAm signatures of the circulating proteome and incident diseases. Using data from four cohorts, we trained and tested epigenetic scores (EpiScores) for 953 plasma proteins, identifying 109 scores that explained between 1% and 58% of the variance in protein levels after adjusting for known protein quantitative trait loci (pQTL) genetic effects. By projecting these EpiScores into an independent s le, (Generation Scotland n=9,537) and relating them to incident morbidities over a follow-up of 14 years, we uncovered 137 EpiScore – disease associations. These associations were largely independent of immune cell proportions, common lifestyle and health factors and biological aging. Notably, we found that our diabetes-associated EpiScores highlighted previous top biomarker associations from proteome-wide assessments of diabetes. These EpiScores for protein levels can therefore be a valuable resource for disease prediction and risk stratification.
No related grants have been discovered for Elliot M. Tucker-Drob.