| 1. |
- Li, Jian-Liang, et al.
(author)
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A genome scan for modifiers of age at onset in Huntington disease : The HD MAPS study.
- 2003
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In: American Journal of Human Genetics. - : Elsevier BV. - 0002-9297 .- 1537-6605. ; 73:3, s. 682-7
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Journal article (peer-reviewed)abstract
- Huntington disease (HD) is caused by the expansion of a CAG repeat within the coding region of a novel gene on 4p16.3. Although the variation in age at onset is partly explained by the size of the expanded repeat, the unexplained variation in age at onset is strongly heritable (h2=0.56), which suggests that other genes modify the age at onset of HD. To identify these modifier loci, we performed a 10-cM density genomewide scan in 629 affected sibling pairs (295 pedigrees and 695 individuals), using ages at onset adjusted for the expanded and normal CAG repeat sizes. Because all those studied were HD affected, estimates of allele sharing identical by descent at and around the HD locus were adjusted by a positionally weighted method to correct for the increased allele sharing at 4p. Suggestive evidence for linkage was found at 4p16 (LOD=1.93), 6p21-23 (LOD=2.29), and 6q24-26 (LOD=2.28), which may be useful for investigation of genes that modify age at onset of HD.
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| 2. |
- 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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| 3. |
- 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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| 4. |
- 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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| 5. |
- Szatmari, Peter, et al.
(author)
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Mapping autism risk loci using genetic linkage and chromosomal rearrangements.
- 2007
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In: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 39:3, s. 319-328
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Journal article (peer-reviewed)abstract
- Autism spectrum disorders (ASDs) are common, heritable neurodevelopmental conditions. The genetic architecture of ASDs is complex, requiring large samples to overcome heterogeneity. Here we broaden coverage and sample size relative to other studies of ASDs by using Affymetrix 10K SNP arrays and 1,168 families with at least two affected individuals, performing the largest linkage scan to date while also analyzing copy number variation in these families. Linkage and copy number variation analyses implicate chromosome 11p12-p13 and neurexins, respectively, among other candidate loci. Neurexins team with previously implicated neuroligins for glutamatergic synaptogenesis, highlighting glutamate-related genes as promising candidates for contributing to ASDs.
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| 6. |
- Chen, Gongbo, et al.
(author)
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All-cause, cardiovascular, and respiratory mortality and wildfire-related ozone : a multicountry two-stage time series analysis
- 2024
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In: The Lancet Planetary Health. - : Elsevier. - 2542-5196. ; 8:7, s. e452-e462
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Journal article (peer-reviewed)abstract
- Background: Wildfire activity is an important source of tropospheric ozone (O3) pollution. However, no study to date has systematically examined the associations of wildfire-related O3 exposure with mortality globally.Methods: We did a multicountry two-stage time series analysis. From the Multi-City Multi-Country (MCC) Collaborative Research Network, data on daily all-cause, cardiovascular, and respiratory deaths were obtained from 749 locations in 43 countries or areas, representing overlapping periods from Jan 1, 2000, to Dec 31, 2016. We estimated the daily concentration of wildfire-related O3 in study locations using a chemical transport model, and then calibrated and downscaled O3 estimates to a resolution of 0·25° × 0·25° (approximately 28 km2 at the equator). Using a random-effects meta-analysis, we examined the associations of short-term wildfire-related O3 exposure (lag period of 0–2 days) with daily mortality, first at the location level and then pooled at the country, regional, and global levels. Annual excess mortality fraction in each location attributable to wildfire-related O3 was calculated with pooled effect estimates and used to obtain excess mortality fractions at country, regional, and global levels.Findings: Between 2000 and 2016, the highest maximum daily wildfire-related O3 concentrations (≥30 μg/m3) were observed in locations in South America, central America, and southeastern Asia, and the country of South Africa. Across all locations, an increase of 1 μg/m3 in the mean daily concentration of wildfire-related O3 during lag 0–2 days was associated with increases of 0·55% (95% CI 0·29 to 0·80) in daily all-cause mortality, 0·44% (–0·10 to 0·99) in daily cardiovascular mortality, and 0·82% (0·18 to 1·47) in daily respiratory mortality. The associations of daily mortality rates with wildfire-related O3 exposure showed substantial geographical heterogeneity at the country and regional levels. Across all locations, estimated annual excess mortality fractions of 0·58% (95% CI 0·31 to 0·85; 31 606 deaths [95% CI 17 038 to 46 027]) for all-cause mortality, 0·41% (–0·10 to 0·91; 5249 [–1244 to 11 620]) for cardiovascular mortality, and 0·86% (0·18 to 1·51; 4657 [999 to 8206]) for respiratory mortality were attributable to short-term exposure to wildfire-related O3.Interpretation: In this study, we observed an increase in all-cause and respiratory mortality associated with short-term wildfire-related O3 exposure. Effective risk and smoke management strategies should be implemented to protect the public from the impacts of wildfires.
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| 7. |
- Chen, Gongbo, et al.
(author)
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Mortality risk attributable to wildfire-related PM2·5 pollution : a global time series study in 749 locations
- 2021
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In: The Lancet Planetary Health. - : Elsevier. - 2542-5196. ; 5:9, s. e579-e587
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Journal article (peer-reviewed)abstract
- BACKGROUND: Many regions of the world are now facing more frequent and unprecedentedly large wildfires. However, the association between wildfire-related PM2·5 and mortality has not been well characterised. We aimed to comprehensively assess the association between short-term exposure to wildfire-related PM2·5 and mortality across various regions of the world.METHODS: For this time series study, data on daily counts of deaths for all causes, cardiovascular causes, and respiratory causes were collected from 749 cities in 43 countries and regions during 2000-16. Daily concentrations of wildfire-related PM2·5 were estimated using the three-dimensional chemical transport model GEOS-Chem at a 0·25° × 0·25° resolution. The association between wildfire-related PM2·5 exposure and mortality was examined using a quasi-Poisson time series model in each city considering both the current-day and lag effects, and the effect estimates were then pooled using a random-effects meta-analysis. Based on these pooled effect estimates, the population attributable fraction and relative risk (RR) of annual mortality due to acute wildfire-related PM2·5 exposure was calculated.FINDINGS: 65·6 million all-cause deaths, 15·1 million cardiovascular deaths, and 6·8 million respiratory deaths were included in our analyses. The pooled RRs of mortality associated with each 10 μg/m3 increase in the 3-day moving average (lag 0-2 days) of wildfire-related PM2·5 exposure were 1·019 (95% CI 1·016-1·022) for all-cause mortality, 1·017 (1·012-1·021) for cardiovascular mortality, and 1·019 (1·013-1·025) for respiratory mortality. Overall, 0·62% (95% CI 0·48-0·75) of all-cause deaths, 0·55% (0·43-0·67) of cardiovascular deaths, and 0·64% (0·50-0·78) of respiratory deaths were annually attributable to the acute impacts of wildfire-related PM2·5 exposure during the study period.INTERPRETATION: Short-term exposure to wildfire-related PM2·5 was associated with increased risk of mortality. Urgent action is needed to reduce health risks from the increasing wildfires.
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| 8. |
- Djoussé, Luc, et al.
(author)
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Evidence for a modifier of onset age in Huntington disease linked to the HD gene in 4p16.
- 2004
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In: Neurogenetics. - : Springer Science and Business Media LLC. - 1364-6745 .- 1364-6753. ; 5:2, s. 109-14
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Journal article (peer-reviewed)abstract
- Huntington disease (HD) is a neurodegenerative disorder caused by the abnormal expansion of CAG repeats in the HD gene on chromosome 4p16.3. A recent genome scan for genetic modifiers of age at onset of motor symptoms (AO) in HD suggests that one modifier may reside in the region close to the HD gene itself. We used data from 535 HD participants of the New England Huntington cohort and the HD MAPS cohort to assess whether AO was influenced by any of the three markers in the 4p16 region: MSX1 (Drosophila homeo box homologue 1, formerly known as homeo box 7, HOX7), Delta2642 (within the HD coding sequence), and BJ56 ( D4S127). Suggestive evidence for an association was seen between MSX1 alleles and AO, after adjustment for normal CAG repeat, expanded repeat, and their product term (model P value 0.079). Of the variance of AO that was not accounted for by HD and normal CAG repeats, 0.8% could be attributed to the MSX1 genotype. Individuals with MSX1 genotype 3/3 tended to have younger AO. No association was found between Delta2642 (P=0.44) and BJ56 (P=0.73) and AO. This study supports previous studies suggesting that there may be a significant genetic modifier for AO in HD in the 4p16 region. Furthermore, the modifier may be present on both HD and normal chromosomes bearing the 3 allele of the MSX1 marker.
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| 9. |
- Kuiper, Ingrid Nordeide, et al.
(author)
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Lung health in adulthood after childhood exposure to air pollution and greenness
- 2018
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In: European Respiratory Journal. - : European Respiratory Society. - 0903-1936 .- 1399-3003. ; 52
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Journal article (other academic/artistic)abstract
- Background: Little is known on childhood exposure to air pollution and adult chronic respiratory outcomes.Aim: To investigate associations between air pollution and greenness in childhood and adult lung health.Methods: In selected centres of the RHINESSA study (age 18-52) we analysed the outcomes respiratory symptoms (≥3 symptoms), severe wheeze (wheeze last year with breathlessness, no cold) and late onset asthma (>10 years). We calculated mean annual exposures of PM2.5, PM10, NO2 (µg/m³) and greenness (Normalized Difference Vegetation Index, 100m buffer) from offspring's birth till age 18, categorised into mean exposure <10 years and 11-18 years. We performed multilevel logistic regression clustered by family, stratified by centre and adjusted for childhood passive smoke and parental asthma.Results: 12% had ≥3 respiratory symptoms, 7.7% severe wheeze, and 9.4% late onset asthma. Overall estimates: greenness was associated with less respiratory symptoms, PM2.5 and NO2 with more late onset asthma. Exposure <10 years: Greenness was associated with less wheeze in Tartu (OR 0.29, 95%CI 0.11-0.73). PM2.5 (OR 1.22, 95%CI 1.00-1.48) and NO2 (OR 1.06, 95%CI 1.01-1.11) were risk factors for late onset asthma in Bergen. PM10 was a risk factor for respiratory symptoms (OR 1.21, 95%CI 1.04-1.41) in Uppsala and late onset asthma (OR 1.23, 95%CI 1.02-1.45) in Bergen. Exposure 11-18 years: Greenness was protective for respiratory symptoms (OR 0.29, 95%CI 0.10-0.86) and wheeze (OR 0.39, 95%CI 0.19-0.80) in Tartu.Conclusions: Childhood exposure to greenness was associated with less respiratory symptoms, while air pollutants were associated with more respiratory symptoms (some centres) and late onset asthma.
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| 10. |
- Ramasamy, Adaikalavan, et al.
(author)
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Genome-Wide Association Studies of Asthma in Population-Based Cohorts Confirm Known and Suggested Loci and Identify an Additional Association near HLA
- 2012
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In: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 7:9, s. e44008-
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Journal article (peer-reviewed)abstract
- Rationale: Asthma has substantial morbidity and mortality and a strong genetic component, but identification of genetic risk factors is limited by availability of suitable studies. Objectives: To test if population-based cohorts with self-reported physician-diagnosed asthma and genome-wide association (GWA) data could be used to validate known associations with asthma and identify novel associations. Methods: The APCAT (Analysis in Population-based Cohorts of Asthma Traits) consortium consists of 1,716 individuals with asthma and 16,888 healthy controls from six European-descent population-based cohorts. We examined associations in APCAT of thirteen variants previously reported as genome-wide significant (P < 5x10(-8)) and three variants reported as suggestive (P < 5 x 10(-7)). We also searched for novel associations in APCAT (Stage 1) and followed-up the most promising variants in 4,035 asthmatics and 11,251 healthy controls (Stage 2). Finally, we conducted the first genome-wide screen for interactions with smoking or hay fever. Main Results: We observed association in the same direction for all thirteen previously reported variants and nominally replicated ten of them. One variant that was previously suggestive, rs11071559 in RORA, now reaches genome-wide significance when combined with our data (P = 2.4x10(-9)). We also identified two genome-wide significant associations: rs13408661 near IL1RL1/IL18R1 (PStage1+Stage2 = 1.1x10(-9)), which is correlated with a variant recently shown to be associated with asthma (rs3771180), and rs9268516 in the HLA region (PStage1+Stage2 = 1.1x10(-8)), which appears to be independent of previously reported associations in this locus. Finally, we found no strong evidence for gene-environment interactions with smoking or hay fever status. Conclusions: Population-based cohorts with simple asthma phenotypes represent a valuable and largely untapped resource for genetic studies of asthma.
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