| 1. |
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| 2. |
- Silventoinen, K., et al.
(author)
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The CODATwins Project : The current status and recent findings of COllaborative Project of Development of Anthropometrical Measures in Twins
- 2019
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In: Twin Research and Human Genetics. - : Cambridge University Press. - 1832-4274 .- 1839-2628. ; 22:6, s. 800-808
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Journal article (peer-reviewed)abstract
- The COllaborative project of Development of Anthropometrical measures in Twins (CODATwins) project is a large international collaborative effort to analyze individual-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/m2) 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 individual-level data. The CODATwins database includes 489,981 twin individuals (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 sample sizes and address the effects of different exposures across time, geographical regions and socioeconomic status.
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| 3. |
- Jelenkovic, A., et al.
(author)
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Genetic and environmental influences on adult human height across birth cohorts from 1886 to 1994
- 2016
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In: eLIFE. - Cambridge, United Kingdom : eLife Sciences Publications. - 2050-084X. ; 5
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Journal article (peer-reviewed)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 individual-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.
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| 4. |
- Silventoinen, K., et al.
(author)
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Differences in genetic and environmental variation in adult BMI by sex, age, time period, and region : An individual-based pooled analysis of 40 twin cohorts
- 2017
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In: American Journal of Clinical Nutrition. - : Oxford University Press. - 0002-9165 .- 1938-3207. ; 106:2, s. 457-466
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Journal article (peer-reviewed)abstract
- Background: Genes and the environment contribute to variation in adult body mass index [BMI (in kg/m2)], but factors modifying these variance components are poorly understood.Objective: We analyzed genetic and environmental variation in BMI between men and women from young adulthood to old age from the 1940s to the 2000s and between cultural-geographic regions representing high (North America and Australia), moderate (Europe), and low (East Asia) prevalence of obesity.Design: We used genetic structural equation modeling to analyze BMI in twins ≥20 y of age from 40 cohorts representing 20 countries (140,379 complete twin pairs).Results: The heritability of BMI decreased from 0.77 (95% CI: 0.77, 0.78) and 0.75 (95% CI: 0.74, 0.75) in men and women 20-29 y of age to 0.57 (95% CI: 0.54, 0.60) and 0.59 (95% CI: 0.53, 0.65) in men 70-79 y of age and women 80 y of age, respectively. The relative influence of unique environmental factors correspondingly increased. Differences in the sets of genes affecting BMI in men and women increased from 20-29 to 60-69 y of age. Mean BMI and variances in BMI increased from the 1940s to the 2000s and were greatest in North America and Australia, followed by Europe and East Asia. However, heritability estimates were largely similar over measurement years and between regions. There was no evidence of environmental factors shared by co-twins affecting BMI.Conclusions: The heritability of BMI decreased and differences in the sets of genes affecting BMI in men and women increased from young adulthood to old age. The heritability of BMI was largely similar between cultural-geographic regions and measurement years, despite large differences in mean BMI and variances in BMI. Our results show a strong influence of genetic factors on BMI, especially in early adulthood, regardless of the obesity level in the population.
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| 5. |
- Piirtola, M., et al.
(author)
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Association of current and former smoking with body mass index : A study of smoking discordant twin pairs from 21 twin cohorts
- 2018
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In: PLOS ONE. - : Public Library of Science. - 1932-6203. ; 13:7
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Journal article (peer-reviewed)abstract
- Background Smokers tend to weigh less than never smokers, while successful quitting leads to an increase in body weight. Because smokers and non-smokers may differ in genetic and environmental family background, we analysed data from twin pairs in which the co-twins differed by their smoking behaviour to evaluate if the association between smoking and body mass index (BMI) remains after controlling for family background.Methods and findings The international CODATwins database includes information on smoking and BMI measured between 1960 and 2012 from 156,593 twin individuals 18–69 years of age. Individual-based data (230,378 measurements) and data of smoking discordant twin pairs (altogether 30,014 pairwise measurements, 36% from monozygotic [MZ] pairs) were analysed with linear fixed-effects regression models by 10-year periods. In MZ pairs, the smoking co-twin had, on average, 0.57 kg/m2 lower BMI in men (95% confidence interval (CI): 0.49, 0.70) and 0.65 kg/m2 lower BMI in women (95% CI: 0.52, 0.79) than the never smoking co-twin. Former smokers had 0.70 kg/m2 higher BMI among men (95% CI: 0.63, 0.78) and 0.62 kg/ m2 higher BMI among women (95% CI: 0.51, 0.73) than their currently smoking MZ co-twins. Little difference in BMI was observed when comparing former smoking co-twins with their never smoking MZ co-twins (0.13 kg/m2, 95% CI 0.04, 0.23 among men; -0.04 kg/m2, 95% CI -0.16, 0.09 among women). The associations were similar within dizygotic pairs and when analysing twins as individuals. The observed series of cross-sectional associations were independent of sex, age, and measurement decade.ConclusionsSmoking is associated with lower BMI and smoking cessation with higher BMI. However, the net effect of smoking and subsequent cessation on weight development appears to be minimal, i.e. never more than an average of 0.7 kg/m2
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| 6. |
- Luczak, S. E., et al.
(author)
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Remember this : Age moderation of genetic and environmental contributions to verbal episodic memory from midlife through late adulthood
- 2023
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In: Intelligence. - : Elsevier. - 0160-2896 .- 1873-7935. ; 99
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Journal article (peer-reviewed)abstract
- It is well documented that memory is heritable and that older adults tend to have poorer memory performance than younger adults. However, whether the magnitudes of genetic and environmental contributions to late-life verbal episodic memory ability differ from those at earlier ages remains unresolved. Twins from 12 studies participating in the Interplay of Genes and Environment in Multiple Studies (IGEMS) consortium constituted the analytic sample. Verbal episodic memory was assessed with immediate word list recall (N = 35,204 individuals; 21,792 twin pairs) and prose recall (N = 3805 individuals; 2028 twin pairs), with scores harmonized across studies. Average test performance was lower in successively older age groups for both measures. Twin models found significant age moderation for both measures, with total inter-individual variance increasing significantly with age, although it was not possible definitively to attribute the increase specifically to either genetic or environmental sources. Pooled results across all 12 studies were compared to results where we successively dropped each study (leave-one-out) to assure results were not due to an outlier. We conclude the models indicated an overall increase in variance for verbal episodic memory that was driven by a combination of increases in the genetic and nonshared environmental parameters that were not independently statistically significant. In contrast to reported results for other cognitive domains, differences in environmental exposures are comparatively important for verbal episodic memory, especially word list learning.
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| 7. |
- Jelenkovic, A, et al.
(author)
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Genetic and environmental influences on height from infancy to early adulthood: An individual-based pooled analysis of 45 twin cohorts
- 2016
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In: Scientific reports. - London, United Kingdom : Springer Science and Business Media LLC. - 2045-2322. ; 6, s. 28496-
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Journal article (peer-reviewed)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 individual-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.
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| 8. |
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| 9. |
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| 10. |
- Beam, Christopher R., et al.
(author)
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Estimating Likelihood of Dementia in the Absence of Diagnostic Data : A Latent Dementia Index in 10 Genetically Informed Studies
- 2022
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In: Journal of Alzheimer's Disease. - : IOS Press. - 1387-2877 .- 1875-8908. ; 90:3, s. 1187-1201
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Journal article (peer-reviewed)abstract
- BACKGROUND: Epidemiological research on dementia is hampered by differences across studies in how dementia is classified, especially where clinical diagnoses of dementia may not be available. OBJECTIVE: We apply structural equation modeling to estimate dementia likelihood across heterogeneous samples within a multi-study consortium and use the twin design of the sample to validate the results. METHODS: Using 10 twin studies, we implement a latent variable approach that aligns different tests available in each study to assess cognitive, memory, and functional ability. The model separates general cognitive ability from components indicative of dementia. We examine the validity of this continuous latent dementia index (LDI). We then identify cut-off points along the LDI distributions in each study and align them across studies to distinguish individuals with and without probable dementia. Finally, we validate the LDI by determining its heritability and estimating genetic and environmental correlations between the LDI and clinically diagnosed dementia where available. RESULTS: Results indicate that coordinated estimation of LDI across 10 studies has validity against clinically diagnosed dementia. The LDI can be fit to heterogeneous sets of memory, other cognitive, and functional ability variables to extract a score reflective of likelihood of dementia that can be interpreted similarly across studies despite diverse study designs and sampling characteristics. Finally, the same genetic sources of variance strongly contribute to both the LDI and clinical diagnosis. CONCLUSION: This latent dementia indicator approach may serve as a model for other research consortia confronted with similar data integration challenges.
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| 11. |
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| 12. |
- Jelenkovic, A, et al.
(author)
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Genetic and environmental influences on human height from infancy through adulthood at different levels of parental education
- 2020
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In: Scientific reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 10:1, s. 7974-
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Journal article (peer-reviewed)abstract
- Genetic factors explain a major proportion of human height variation, but differences in mean stature have also been found between socio-economic categories suggesting a possible effect of environment. By utilizing a classical twin design which allows decomposing the variation of height into genetic and environmental components, we tested the hypothesis that environmental variation in height is greater in offspring of lower educated parents. Twin data from 29 cohorts including 65,978 complete twin pairs with information on height at ages 1 to 69 years and on parental education were pooled allowing the analyses at different ages and in three geographic-cultural regions (Europe, North America and Australia, and East Asia). Parental education mostly showed a positive association with offspring height, with significant associations in mid-childhood and from adolescence onwards. In variance decomposition modeling, the genetic and environmental variance components of height did not show a consistent relation to parental education. A random-effects meta-regression analysis of the aggregate-level data showed a trend towards greater shared environmental variation of height in low parental education families. In conclusion, in our very large dataset from twin cohorts around the globe, these results provide only weak evidence for the study hypothesis.
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| 13. |
- Silventoinen, Karri, et al.
(author)
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Education in twins and their parents across birth cohorts over 100 years : an individual-level pooled analysis of 42 twin cohorts
- 2017
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In: Twin Research and Human Genetics. - Stockholm : Karolinska Institutet, Dept of Medical Epidemiology and Biostatistics. - 1832-4274 .- 1839-2628.
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Journal article (peer-reviewed)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 individual, maternal and paternal education between MZ and DZ twins in a large pooled dataset. Information was gathered on individual 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 individual 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 individual 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.
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| 14. |
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| 15. |
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| 16. |
- Finkel, Deborah, et al.
(author)
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Age and sex differences in the genetic architecture of measures of subjective health : Relationships with physical health, depressive symptoms, and episodic memory
- 2024
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In: The journals of gerontology. Series B, Psychological sciences and social sciences. - : Oxford University Press. - 1079-5014 .- 1758-5368.
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Journal article (peer-reviewed)abstract
- OBJECTIVES: Subjective health (SH) is not just an indicator of physical health, but also reflects active cognitive processing of information about one's own health and has been associated with emotional health measures, such as neuroticism and depression. Behavior genetic approaches investigate the genetic architecture of SH, i.e., genetic and environmental influences on individual differences in SH and associations with potential components such as physical, cognitive, and emotional health. Previous twin analyses have been limited by sex, sample size, age range, and focus on single covariates.METHODS: The current analysis used data from 24,173 adults ranging in age from 40-90 years from the international Interplay of Genes and Environment Across Multiple Studies (IGEMS) consortium to investigate the genetic architecture of three measures of SH: self-rated health, health compared to others, and impact of health on activities. Independent pathways model of SH included physical health, depressive symptoms, and episodic memory, with age, sex, and country included as covariates.RESULTS: Most or all of the genetic variance for SH measures was shared with physical health, depressive symptoms, and episodic memory. Genetic architecture of SH differed across measures, age groups (40-65, 66-90), and sexes. Age comparisons indicated stronger correlations with all 3 covariates in older adults, often resulting from greater shared genetic variance.DISCUSSION: The predictive value of SH has been amply demonstrated. The higher genetic contributions to associations between SH and its components in older adults support the increasing conceptualization with age of SH as an intuitive summation of one's vital reserve.
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| 17. |
- Jelenkovic, Aline, et al.
(author)
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Zygosity Differences in Height and Body Mass Index of Twins From Infancy to Old Age : A Study of the CODATwins Project
- 2015
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In: Twin Research and Human Genetics. - : Cambridge University Press. - 1832-4274 .- 1839-2628. ; 18:5, s. 557-570
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Journal article (peer-reviewed)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.
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| 18. |
- Lichtenstein, P, et al.
(author)
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The Swedish Twin Registry in the third millennium: an update
- 2006
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In: Twin research and human genetics : the official journal of the International Society for Twin Studies. - : Cambridge University Press (CUP). - 1832-4274. ; 9:6, s. 875-882
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Journal article (peer-reviewed)abstract
- The Swedish Twin Registry was first established in the late 1950s. Today it includes more than 170,000 twins — in principle all twins born in Sweden since 1886. In this article we describe some ongoing and recently completed projects based on the registry. In particular, we describe recent efforts to screen all twins born between 1959 and 1985, and young twin pairs when they turn 9 and 12 years of age. For these studies, we present initial frequencies of common conditions and exposures.
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| 19. |
- Pahlen, Shandell, et al.
(author)
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Age-moderation of genetic and environmental contributions to cognitive functioning in mid- and late-life for specific cognitive abilities
- 2018
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In: Intelligence. - : Elsevier. - 0160-2896 .- 1873-7935. ; 68, s. 70-81
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Journal article (peer-reviewed)abstract
- Age moderation of genetic and environmental contributions to Digits Forward, Digits Backward, Block Design, Symbol Digit, Vocabulary, and Synonyms was investigated in a sample of 14,534 twins aged 26 to 98 years. The Interplay of Genes and Environment across Multiple Studies (IGEMS) consortium contributed the sample, which represents nine studies from three countries (USA, Denmark, and Sweden). Average test performance was lower in successively older age groups for all tests. Significant age moderation of additive genetic, shared environmental, and non-shared environmental variance components was observed, but the pattern varied by test. The genetic contribution to phenotypic variance across age was smaller for both Digit Span tests, greater for Synonyms, and stable for Block Design and Symbol Digit. The non-shared environmental contribution was greater with age for the Digit Span tests and Block Design, while the shared environmental component was small for all tests, often more so with age. Vocabulary showed similar age-moderation patterns as Synonyms, but these effects were nonsignificant. Findings are discussed in the context of theories of cognitive aging.
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| 20. |
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| 21. |
- Read, S, et al.
(author)
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Sex differences after all those years? Heritability of cognitive abilities in old age
- 2006
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In: Journal of Gerontology: Psychological Sciences. ; , s. 137-143
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Journal article (peer-reviewed)abstract
- We investigated sex differences in genetic and environmental effects on cognitive abilities among older adult twins. We drew participants from the Swedish Twin Registry; our sample included 647 twin pairs. Our cognitive measures included Synonyms, Block Design, Digit Span, Thurstone's Picture Memory, Symbol Digit, and general cognitive ability tests. Higher age was related to lower performance in all cognitive measures, except synonyms. For digit span forward, symbol digit, and general cognitive ability tasks, there was a Sex x Age interac-tion, with greater deficits in the performance of women compared with those of men at higher ages. We found no sex-specific genetic influences. In other words, the same genetic effects were operating for men and women. Furthermore, the magnitude of genetic effect was similar for men and women.
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| 22. |
- Silventoinen, Karri, et al.
(author)
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Genetic and environmental variation in educational attainment : an individual-based analysis of 28 twin cohorts
- 2020
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In: Scientific Reports. - : Springer Nature. - 2045-2322. ; 10:1
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Journal article (peer-reviewed)abstract
- We investigated the heritability of educational attainment and how it differed between birth cohorts and cultural–geographic regions. A classical twin design was applied to pooled data from 28 cohorts representing 16 countries and including 193,518 twins with information on educational attainment at 25 years of age or older. Genetic factors explained the major part of individual differences in educational attainment (heritability: a2 = 0.43; 0.41–0.44), but also environmental variation shared by co-twins was substantial (c2 = 0.31; 0.30–0.33). The proportions of educational variation explained by genetic and shared environmental factors did not differ between Europe, North America and Australia, and East Asia. When restricted to twins 30 years or older to confirm finalized education, the heritability was higher in the older cohorts born in 1900–1949 (a2 = 0.44; 0.41–0.46) than in the later cohorts born in 1950–1989 (a2 = 0.38; 0.36–0.40), with a corresponding lower influence of common environmental factors (c2 = 0.31; 0.29–0.33 and c2 = 0.34; 0.32–0.36, respectively). In conclusion, both genetic and environmental factors shared by co-twins have an important influence on individual differences in educational attainment. The effect of genetic factors on educational attainment has decreased from the cohorts born before to those born after the 1950s.
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| 23. |
- Silventoinen, Karri, et al.
(author)
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Smoking remains associated with education after controlling for social background and genetic factors in a study of 18 twin cohorts
- 2022
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In: Scientific Reports. - : Nature Portfolio. - 2045-2322. ; 12:1
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Journal article (peer-reviewed)abstract
- We tested the causality between education and smoking using the natural experiment of discordant twin pairs allowing to optimally control for background genetic and childhood social factors. Data from 18 cohorts including 10,527 monozygotic (MZ) and same-sex dizygotic (DZ) twin pairs discordant for education and smoking were analyzed by linear fixed effects regression models. Within twin pairs, education levels were lower among the currently smoking than among the never smoking co-twins and this education difference was larger within DZ than MZ pairs. Similarly, education levels were higher among former smoking than among currently smoking co-twins, and this difference was larger within DZ pairs. Our results support the hypothesis of a causal effect of education on both current smoking status and smoking cessation. However, the even greater intra-pair differences within DZ pairs, who share only 50% of their segregating genes, provide evidence that shared genetic factors also contribute to these associations.
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| 24. |
- Silventoinen, Karri, et al.
(author)
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The CODATwins Project : The Cohort Description of Collaborative Project of Development of Anthropometrical Measures in Twins to Study Macro-Environmental Variation in Genetic and Environmental Effects on Anthropometric Traits
- 2015
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In: Twin Research and Human Genetics. - : Cambridge University Press. - 1832-4274 .- 1839-2628. ; 18:4
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Journal article (peer-reviewed)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/m2) 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 individual 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 individuals, 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.
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| 25. |
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| 26. |
- Finkel, Deborah, et al.
(author)
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Financial strain moderates genetic influences on self-rated health : support for diathesis–stress model of gene–environment interplay
- 2022
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In: Biodemography and Social Biology. - : Taylor & Francis. - 1948-5565 .- 1948-5573. ; 67:1, s. 58-70
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Journal article (peer-reviewed)abstract
- Data from the Interplay of Genes and Environment across Multiple Studies (IGEMS) consortium were used to examine predictions of different models of gene-by-environment interaction to understand how genetic variance in self-rated health (SRH) varies at different levels of financial strain. A total of 11,359 individuals from 10 twin studies in Australia, Sweden, and the United States contributed relevant data, including 2,074 monozygotic and 2,623 dizygotic twin pairs. Age ranged from 22 to 98 years, with a mean age of 61.05 (SD = 13.24). A factor model was used to create a harmonized measure of financial strain across studies and items. Twin analyses of genetic and environmental variance for SRH incorporating age, age2, sex, and financial strain moderators indicated significant financial strain moderation of genetic influences on self-rated health. Moderation results did not differ across sex or country. Genetic variance for SRH increased as financial strain increased, matching the predictions of the diathesis–stress and social comparison models for components of variance. Under these models, environmental improvements would be expected to reduce genetically based health disparities.
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| 27. |
- Gatz, M, et al.
(author)
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Accounting for the relationship between low education and dementia: a twin study.
- 2007
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In: Physiol Behav. ; , s. 232-237
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Journal article (peer-reviewed)abstract
- We evaluated whether the association between low education and greater risk of dementia is explained by genetic influences, using three different types of analyses. The HARMONY study (Swedish for "health" (Hälsa), "genes" (ARv), "environment" (Miljö), "and" (Och), and "new" (NY)) includes members of the Swedish Twin Registry who were aged 65 and older and alive in 1998, and who were screened and clinically assessed for dementia. There were 394 cases with dementia and 7786 unrelated controls. Analyses included co-twin control, tests for association between education and a measured genotype, and bivariate twin modeling. Low education was a significant risk factor for dementia both in case-control analyses (odds ratio=1.77, 95% confidence interval 1.38 to 2.28) and co-twin control analyses with monozygotic twin pairs (odds ratio=3.17, 95% confidence interval 1.26 to 7.93). Apolipoprotein E genotype was not associated with education and did not account for the relationship between education and dementia. Bivariate twin modeling showed that the association between education and dementia was not mediated by genetic influences in common between education and dementia. The association was mediated by shared environmental influences that were related to both dementia and to education. Low education is confirmed as a risk factor for dementia. Findings from three different analytic approaches showed that genetic influences did not explain this association.
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| 35. |
- Hou, JH, et al.
(author)
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Polygenic resilience scores capture protective genetic effects for Alzheimer's disease
- 2022
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In: Translational psychiatry. - : Springer Science and Business Media LLC. - 2158-3188. ; 12:1, s. 296-
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Journal article (peer-reviewed)abstract
- Polygenic risk scores (PRSs) can boost risk prediction in late-onset Alzheimer’s disease (LOAD) beyond apolipoprotein E (APOE) but have not been leveraged to identify genetic resilience factors. Here, we sought to identify resilience-conferring common genetic variants in (1) unaffected individuals having high PRSs for LOAD, and (2) unaffected APOE-ε4 carriers also having high PRSs for LOAD. We used genome-wide association study (GWAS) to contrast “resilient” unaffected individuals at the highest genetic risk for LOAD with LOAD cases at comparable risk. From GWAS results, we constructed polygenic resilience scores to aggregate the addictive contributions of risk-orthogonal common variants that promote resilience to LOAD. Replication of resilience scores was undertaken in eight independent studies. We successfully replicated two polygenic resilience scores that reduce genetic risk penetrance for LOAD. We also showed that polygenic resilience scores positively correlate with polygenic risk scores in unaffected individuals, perhaps aiding in staving off disease. Our findings align with the hypothesis that a combination of risk-independent common variants mediates resilience to LOAD by moderating genetic disease risk.
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| 36. |
- Jansson, M, et al.
(author)
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Gender differences in heritability of depressive symptoms in the elderly
- 2004
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In: PSYCHOLOGICAL MEDICINE. - 0033-2917 .- 1469-8978. ; 34:3, s. 471-479
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Journal article (peer-reviewed)abstract
- BACKGROUND: The present study aimed to investigate the relative importance of genetic and environmental influences on depressive symptoms in the elderly. METHOD: Depressive symptoms were assessed through the Center for Epidemiological Studies-Depression (CES-D) scale. The CES-D scale was administered to 959 twin pairs (123 female MZs, 90 male MZs, 207 same-sex female DZs, 109 same-sex male DZs and 430 opposite-sex DZs) aged 50 years or older (mean age 72 years). A dichotomous depressed state variable was constructed based on CES-D cut-offs and self-reported use of antidepressant medication. Structural equation models were fitted to the data to dissect genetic and environmental variance components. RESULTS: The sex-specific heritability estimates for depressive symptoms were 14% for males and 29% for females and 23% when constrained to be equal for men and women. The prevalence of clinically significant depressive symptoms was 16% for men and 24% for women. Heritability estimates for the dichotomous depressed state measure were 7% for males and 49% for females in the full model and 33% when constrained to be equal. CONCLUSION: Our results suggest that depressive symptoms in the elderly are moderately heritable, with a higher heritability for women than men, although differences in heritability estimates were not statistically significant.
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| 37. |
- Karlsson, Ida K., et al.
(author)
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Genetic susceptibility to cardiovascular disease and risk of dementia
- 2017
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In: Translational Psychiatry. - : Nature Publishing Group. - 2158-3188. ; 7:5
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Journal article (peer-reviewed)abstract
- Several studies have shown cardiovascular disease (CVD) to be associated with dementia, but it is not clear whether CVD per se increases the risk of dementia or whether the association is due to shared risk factors. We tested how a genetic risk score (GRS) for coronary artery disease (CAD) affects dementia risk after CVD in 13 231 Swedish twins. We also utilized summarized genome-wide association data to study genetic overlap between CAD and Alzheimer´s disease (AD), and additionally between shared risk factors and each disease. There was no direct effect of a CAD GRS on dementia (hazard ratio 0.99, 95% confidence interval (CI): 0.98-1.01). However, the GRS for CAD modified the association between CVD and dementia within 3 years of CVD diagnosis, ranging from a hazard ratio of 1.59 (95% CI: 1.05-2.41) in the first GRS quartile to 1.91 (95% CI: 1.28-2.86) in the fourth GRS quartile. Using summary statistics, we found no genetic overlap between CAD and AD. We did, however, find that both AD and CAD share a significant genetic overlap with lipids, but that the overlap arose from clearly distinct gene clusters. In conclusion, genetic susceptibility to CAD was found to modify the association between CVD and dementia, most likely through associations with shared risk factors.
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| 45. |
- Pedersen, N.L, et al.
(author)
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How heritable is Alzheimer's disease in late life? Findings in Swedish twins
- 2004
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In: Annals of neurology. - : Wiley. - 0364-5134 .- 1531-8249. ; 55:2, s. 180-185
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Journal article (peer-reviewed)abstract
- Although genetic effects are known to be important for early onset Alzheimer's disease, little is known about the importance of genetic effects for late-onset disease. Furthermore, previous studies are based on prevalent cases. Our purpose was to characterize the relative importance of genetic and environmental factors for incident Alzheimer's disease late in life, and to test for differences in the importance of genetic effects at different ages. A cohort of 662 pairs of Swedish twins 52 to 98 years of age who were without symptoms of dementia was followed up for an average of 5 years. Incident dementia cases were detected through follow-up at 2 to 3-year intervals using either cognitive testing or telephone screening followed by dementia workups. A physician, psychologist, and nurse gave consensus diagnoses. During the follow-up period, 5.8% of the sample was diagnosed with Alzheimer's disease. Average age of onset was 83.9 years (standard deviation, 6.3). Of the 26 monozygotic pairs in which at least one twin developed Alzheimer's disease, 5 were concordant (probandwise concordance, 32.2%). The concordance rate for dizygotic pairs was 8.7% (2 of 44 pairs). Structural model fitting indicated that 48% of the variation in liability to Alzheimer's disease could be attributed to genetic variation. Estimates did not differ significantly between twins younger than age 80 years and those older than age 80 years at baseline. Although these genetic estimates for incident disease are lower than those for prevalent disease, the importance of genetic factors for liability to Alzheimer's disease is considerable even late in life.
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| 46. |
- Pedersen, N. L., et al.
(author)
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IGEMS: The Consortium on Interplay of Genes and Environment Across Multiple Studies
- 2013
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In: Twin Research and Human Genetics. - : Cambridge University Press (CUP). - 1832-4274 .- 1839-2628. ; 16:1, s. 481-489
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Journal article (peer-reviewed)abstract
- The Interplay of Genes and Environment across Multiple Studies (IGEMS) group is a consortium of eight longitudinal twin studies established to explore the nature of social context effects and gene-environment interplay in late-life functioning. The resulting analysis of the combined data from over 17,500 participants aged 25–102 at baseline (including nearly 2,600 monogygotic and 4,300 dizygotic twin pairs and over 1,700 family members) aims to understand why early life adversity, and social factors such as isolation and loneliness, are associated with diverse outcomes including mortality, physical functioning (health, functional ability), and psychological functioning (well-being, cognition), particularly in later life.
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| 49. |
- Reynolds, Chandra A., et al.
(author)
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Gene-Environment Interplay in Physical, Psychological, and Cognitive Domains in Mid to Late Adulthood : Is APOE a Variability Gene?
- 2016
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In: Behavior Genetics. - : Springer Nature Switzerland AG. - 0001-8244 .- 1573-3297. ; 46:1, s. 4-19
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Journal article (peer-reviewed)abstract
- Despite emerging interest in gene-environment interaction (GxE) effects, there is a dearth of studies evaluating its potential relevance apart from specific hypothesized environments and biometrical variance trends. Using a monozygotic within-pair approach, we evaluated evidence of G×E for body mass index (BMI), depressive symptoms, and cognition (verbal, spatial, attention, working memory, perceptual speed) in twin studies from four countries. We also evaluated whether APOE is a 'variability gene' across these measures and whether it partly represents the 'G' in G×E effects. In all three domains, G×E effects were pervasive across country and gender, with small-to-moderate effects. Age-cohort trends were generally stable for BMI and depressive symptoms; however, they were variable-with both increasing and decreasing age-cohort trends-for different cognitive measures. Results also suggested that APOE may represent a 'variability gene' for depressive symptoms and spatial reasoning, but not for BMI or other cognitive measures. Hence, additional genes are salient beyond APOE.
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| 50. |
- Reynolds, CA, et al.
(author)
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Genotype-environment interactions: cognitive aging and social factors
- 2007
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In: Twin research and human genetics : the official journal of the International Society for Twin Studies. - : Cambridge University Press (CUP). - 1832-4274. ; 10:2, s. 241-254
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Journal article (peer-reviewed)abstract
- The possibility of genotype–environment interaction for memory performance and change was examined in 150 monozygotic (MZ) twin pairs from the Swedish Adoption Twin Study of Aging (SATSA). We used an MZ twin pair difference approach to examine the possibility that genotype was associated with intrapair variability and thus suggestive of genotype–nonshared environment interactions. Multiple ‘variability genes’ were found for longitudinal change in a semantic memory task including candidates coding for apolipoprotein E (APOE) and estrogen receptor alpha (ESR1) as well as serotonin candidates (HTR2Aand5HTT). One candidate also related to variability in change in episodic memory (5HTT). Of the significant associations observed, generally results indicated that MZ pairs who carry putative risk alleles were less variable than noncarriers, suggesting that noncarriers may be more sensitive to environmental contexts. We sought to ‘contextualize’ the possible nonshared environmental influences for found gene–environment (G × E) effects by considering intrapair differences in measured social and stress factors, including social support, life events and depressive symptoms. Results suggested that nonshared environmental influences associated with depressive symptoms may moderate the G × E relationship observed forESR1andAPOEand longitudinal semantic memory change whereby noncarriers of putative risk alleles may be relatively more sensitive to depressionevoking environmental contexts than carriers of the risk allele. Thus, the contexts that facilitate or reduce depressive symptoms may affect semantic memory resiliency dependent on genotype. Further work ought to consider larger sample sizes as well as consider additional social and contextual factors.
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