Estimating the relative contribution of environmental and genetic factors to different aging traits by comprising correlated variables into risk scores

The distribution of recurrent ear infections was obtained from a population-based sample of 2,750 pairs of Norwegian twins born between 1967 and 1974. The lifetime prevalence of self-reported recurrent ear infections was 8.9%, with a significant predominance of female cases. The mean age of onset was 4.2 years, with a gradual decrease in occurrence from 2 to 7 years of age. Among monozygotic pairs, the rate of tetrachoric correlation between co-twins was almost identical in males (0.73, SE 0.08) and females (0.74, SE 0.06), but among the dizygotic pairs the correlation was clearly higher in males (0.53, SE 0.12) than in females (0.20, SE 0.12). The value in the unlike-sexed dizygotic twins (0.25, SE 0.05) was intermediate to that of the like-sexed male and female dizygotic pairs. The relative contribution of genes and environment to variability in the predisposition to develop otitis media was estimated by means of structural equation modeling. Variation in liability to ear infections was mainly explained by additive genetic and dominance factors in females, for whom heritability was estimated at 74%. The remaining 26% of the variation in liability was explained by individual environmental factors. In males, 45% of the variation could be accounted for by genetic factors, 29% by common familial environment, and the remaining 26% by individual environmental effects.

Download Full-text

Progression from islet autoimmunity to clinical type 1 diabetes is influenced by genetic factors: results from the prospective TEDDY study

Journal of Medical Genetics ◽

10.1136/jmedgenet-2018-105532 ◽

2018 ◽

Vol 56 (9) ◽

pp. 602-605 ◽

Cited By ~ 4

Author(s):

Andreas Beyerlein ◽

Ezio Bonifacio ◽

Kendra Vehik ◽

Markus Hippich ◽

Christiane Winkler ◽

...

Keyword(s):

Type 1 Diabetes ◽

Risk Score ◽

Genetic Risk ◽

Genetic Factors ◽

Genetic Risk Score ◽

Risk Scores ◽

Islet Autoimmunity ◽

Islet Autoantibody ◽

Clinical Type

BackgroundProgression time from islet autoimmunity to clinical type 1 diabetes is highly variable and the extent that genetic factors contribute is unknown.MethodsIn 341 islet autoantibody-positive children with the human leucocyte antigen (HLA) DR3/DR4-DQ8 or the HLA DR4-DQ8/DR4-DQ8 genotype from the prospective TEDDY (The Environmental Determinants of Diabetes in the Young) study, we investigated whether a genetic risk score that had previously been shown to predict islet autoimmunity is also associated with disease progression.ResultsIslet autoantibody-positive children with a genetic risk score in the lowest quartile had a slower progression from single to multiple autoantibodies (p=0.018), from single autoantibodies to diabetes (p=0.004), and by trend from multiple islet autoantibodies to diabetes (p=0.06). In a Cox proportional hazards analysis, faster progression was associated with an increased genetic risk score independently of HLA genotype (HR for progression from multiple autoantibodies to type 1 diabetes, 1.27, 95% CI 1.02 to 1.58 per unit increase), an earlier age of islet autoantibody development (HR, 0.68, 95% CI 0.58 to 0.81 per year increase in age) and female sex (HR, 1.94, 95% CI 1.28 to 2.93).ConclusionsGenetic risk scores may be used to identify islet autoantibody-positive children with high-risk HLA genotypes who have a slow rate of progression to subsequent stages of autoimmunity and type 1 diabetes.

Download Full-text

Testing Familial Transmission of Smoking With Two Different Research Designs

Nicotine & Tobacco Research ◽

10.1093/ntr/ntx121 ◽

2017 ◽

Vol 20 (7) ◽

pp. 836-842 ◽

Cited By ~ 1

Author(s):

Jorien L Treur ◽

Karin J H Verweij ◽

Abdel Abdellaoui ◽

Iryna O Fedko ◽

Eveline L de Zeeuw ◽

...

Keyword(s):

The Netherlands ◽

Family Environment ◽

Genetic Risk ◽

Genetic Factors ◽

Environmental Influence ◽

Smoking Initiation ◽

Risk Scores ◽

Environment Interaction ◽

Polygenic Risk ◽

Children Of Twins

Abstract Introduction Classical twin studies show that smoking is heritable. To determine if shared family environment plays a role in addition to genetic factors, and if they interact (G×E), we use a children-of-twins design. In a second sample, we measure genetic influence with polygenic risk scores (PRS) and environmental influence with a question on exposure to smoking during childhood. Methods Data on smoking initiation were available for 723 children of 712 twins from the Netherlands Twin Register (64.9% female, median birth year 1985). Children were grouped in ascending order of risk, based on smoking status and zygosity of their twin-parent and his/her co-twin: never smoking twin-parent with a never smoking co-twin; never smoking twin-parent with a smoking dizygotic co-twin; never smoking twin-parent with a smoking monozygotic co-twin; and smoking twin-parent with a smoking or never smoking co-twin. For 4072 participants from the Netherlands Twin Register (67.3% female, median birth year 1973), PRS for smoking were computed and smoking initiation, smoking heaviness, and exposure to smoking during childhood were available. Results Patterns of smoking initiation in the four group children-of-twins design suggested shared familial influences in addition to genetic factors. PRS for ever smoking were associated with smoking initiation in all individuals. PRS for smoking heaviness were associated with smoking heaviness in individuals exposed to smoking during childhood, but not in non-exposed individuals. Conclusions Shared family environment influences smoking, over and above genetic factors. Genetic risk of smoking heaviness was only important for individuals exposed to smoking during childhood, versus those not exposed (G×E). Implications This study adds to the very few existing children-of-twins (CoT) studies on smoking and combines a CoT design with a second research design that utilizes polygenic risk scores and data on exposure to smoking during childhood. The results show that shared family environment affects smoking behavior over and above genetic factors. There was also evidence for gene–environment interaction (G×E) such that genetic risk of heavy versus light smoking was only important for individuals who were also exposed to (second-hand) smoking during childhood. Together, these findings give additional incentive to recommending parents not to expose their children to cigarette smoking.

Download Full-text

Relative Contributions of Genetic and Non-Genetic Factors on Mosquito Microbiota

10.21203/rs.3.rs-38080/v1 ◽

2020 ◽

Cited By ~ 1

Author(s):

Haikel Nasser Bogale ◽

Matthew V. Cannon ◽

Kalil Keita ◽

Denka Camara ◽

Yaya Barry ◽

...

Keyword(s):

Insecticide Resistance ◽

Bacterial Diversity ◽

Blood Meal ◽

High Throughput Sequencing ◽

Genetic Factors ◽

Resistance Locus ◽

Microbial Composition ◽

Bacterial Composition ◽

Relative Contribution ◽

Main Driver

Abstract Background The commensal microbiota of mosquitoes impacts their development, immunity, and competency, and could provide a target for alternative entomological control approaches. However, despite the importance of the mosquito/microbiota interactions, little is known about the relative contribution of genetic and non-genetic factors in shaping the bacterial communities of mosquitoes. Methods We used a high-throughput sequencing based assay to characterize the bacterial composition and diversity of 665 individual field-caught mosquitoes, as well as their species, genotype at an insecticide resistance locus, blood meal composition, and the eukaryotic parasites and viruses they carry. We then used these data to rigorously estimate the individual effect of each parameter on the bacterial diversity as well as their relative contribution to the microbial composition. Results Overall, multivariate analyses did not reveal any significant contribution of the mosquito species, insecticide resistance or blood meal to the bacterial composition of the mosquitoes surveyed. Infection with parasites and viruses only contributed very marginally and the main driver of the bacterial diversity was the location where each mosquito was collected which explained roughly 20% of the variance observed. Conclusions This analysis shows that, when confounding factors are taken into account, the sites where the mosquitoes are collected is the main driver of the bacterial diversity of wild-caught mosquitoes, although further studies will be needed to determine how the specific components of the local environment affecting the bacterial composition.

Download Full-text

Interactions between dietary patterns and genetic factors in relation to incident dementia among 70-year-olds

European Journal of Nutrition ◽

10.1007/s00394-021-02688-9 ◽

2021 ◽

Author(s):

Jessica Samuelsson ◽

Jenna Najar ◽

Ola Wallengren ◽

Silke Kern ◽

Hanna Wetterberg ◽

...

Keyword(s):

Dietary Patterns ◽

Dietary Pattern ◽

Genetic Factors ◽

Cox Regression ◽

Population Based ◽

Risk Scores ◽

Reduced Rank Regression ◽

Apoe Ε4 ◽

Incident Dementia ◽

Increased Risk

Abstract Purpose To investigate potential interactions between dietary patterns and genetic factors modulating risk for Alzheimer’s disease (AD) in relation to incident dementia. Methods Data were derived from the population-based Gothenburg H70 Birth Cohort Studies in Sweden, including 602 dementia-free 70-year-olds (examined 1992–93, or 2000–02; 64% women) followed for incident dementia until 2016. Two factors from a reduced rank regression analysis were translated into dietary patterns, one healthy (e.g., vegetables, fruit, and fish) and one western (e.g., red meat, refined cereals, and full-fat dairy products). Genetic risk was determined by APOE ε4 status and non-APOE AD-polygenic risk scores (AD-PRSs). Gene–diet interactions in relation to incident dementia were analysed with Cox regression models. The interaction p value threshold was < 0.1. Results There were interactions between the dietary patterns and APOE ε4 status in relation to incident dementia (interaction p value threshold of < 0.1), while no evidence of interactions were found between the dietary patterns and the AD-PRSs. Those with higher adherence to a healthy dietary pattern had a reduced risk of dementia among ε4 non-carriers (HR: 0.77; 95% CI: 0.61; 0.98), but not among ε4 carriers (HR: 0.86; CI: 0.63; 1.18). Those with a higher adherence to the western dietary pattern had an increased risk of dementia among ε4 carriers (HR: 1.37; 95% CI: 1.05; 1.78), while no association was observed among ε4 non-carriers (HR: 0.99; CI: 0.81; 1.21). Conclusions The results of this study suggest that there is an interplay between dietary patterns and APOE ε4 status in relation to incident dementia.

Download Full-text

A Male Monozygotic Twinship Discordant for Homosexuality

The British Journal of Psychiatry ◽

10.1192/bjp.118.547.675 ◽

1971 ◽

Vol 118 (547) ◽

pp. 675-682 ◽

Cited By ~ 15

Author(s):

K. Davison ◽

H. Brierley ◽

C. Smith

Keyword(s):

Environmental Factors ◽

Genetic Factors ◽

Prison Population ◽

Monozygotic Twins ◽

Monozygotic Twin ◽

The Third ◽

Relative Contribution ◽

Quantitative Rating ◽

Genetic And Environmental Factors ◽

Sexual Identification

The relative contribution of genetic and environmental factors to the development of homosexual behaviour is a controversial subject. The original suggestion that homosexuality is a purely inherited trait has been attributed to Krafft-Ebing (Kallmann, 1952). Perhaps the strongest support for this view was Kallmann's series of 40 male monozygotic twin pairs showing 100 per cent concordance for the overt practice and quantitative rating of homosexual behaviour (Kallmann, 1952). This report has been criticized, and Kallmann later conceded that the 100 per cent concordance was possibly a statistical artefact (Kallmann, 1960). Habel (1950), who obtained the index twins from a prison population, found concordant homosexuality in 3 out of 5 monozygotic pairs (60 per cent), but none of 5 dizygotic pairs. In a more recent study, Heston and Shields (1968) found concordant homosexuality in 2 out of 5 monozygotic pairs (40 per cent) and 1 out of 7 dizygotic pairs (14 per cent). Heston and Shields (1968) also report a family with a sibship of 14 which included 3 pairs of male monozygotic twins, in two of which both twins were homosexual and in the third both heterosexual; no environmental factors which differentiated the homosexual from the heterosexual sibs could be detected. These workers also refute the suggestion that the tendency for monozygotic twins to be more alike with regard to homosexuality than dizygotic twins is related not to genetic factors but to problems of sexual identification which predispose to homosexuality (Money, 1962) by pointing out that there is no evidence that monozygotic twins per se are especially prone to become homosexual.

Download Full-text

Quantification of the Relative Contribution of Environmental and Genetic Factors to Variation in Cystic Fibrosis Lung Function

The Journal of Pediatrics ◽

10.1016/j.jpeds.2010.05.018 ◽

2010 ◽

Vol 157 (5) ◽

pp. 802-807.e3 ◽

Cited By ~ 69

Author(s):

J. Michael Collaco ◽

Scott M. Blackman ◽

John McGready ◽

Kathleen M. Naughton ◽

Garry R. Cutting

Keyword(s):

Cystic Fibrosis ◽

Lung Function ◽

Genetic Factors ◽

Cystic Fibrosis Lung ◽

Relative Contribution

Download Full-text

Lower Dietary Intake of Plant Protein Is Associated with Genetic Risk of Diabetes-Related Traits in Urban Asian Indian Adults

Nutrients ◽

10.3390/nu13093064 ◽

2021 ◽

Vol 13 (9) ◽

pp. 3064

Author(s):

Sooad Alsulami ◽

Dhanasekaran Bodhini ◽

Vasudevan Sudha ◽

Coimbatore Subramanian Shanthi Rani ◽

Rajendra Pradeepa ◽

...

Keyword(s):

Genetic Risk ◽

Protein Intake ◽

Asian Indians ◽

Genetic Factors ◽

Risk Allele ◽

Plant Protein ◽

Risk Scores ◽

Nucleotide Polymorphisms ◽

The Impact ◽

Lower Plant

The increasing prevalence of type 2 diabetes among South Asians is caused by a complex interplay between environmental and genetic factors. We aimed to examine the impact of dietary and genetic factors on metabolic traits in 1062 Asian Indians. Dietary assessment was performed using a validated semi-quantitative food frequency questionnaire. Seven single nucleotide polymorphisms (SNPs) from the Transcription factor 7-like 2 and fat mass and obesity-associated genes were used to construct two metabolic genetic risk scores (GRS): 7-SNP and 3-SNP GRSs. Both 7-SNP GRS and 3-SNP GRS were associated with a higher risk of T2D (p = 0.0000134 and 0.008, respectively). The 3-SNP GRS was associated with higher waist circumference (p = 0.010), fasting plasma glucose (FPG) (p = 0.002) and glycated haemoglobin (HbA1c) (p = 0.000066). There were significant interactions between 3-SNP GRS and protein intake (% of total energy intake) on FPG (Pinteraction = 0.011) and HbA1c (Pinteraction = 0.007), where among individuals with lower plant protein intake (<39 g/day) and those with >1 risk allele had higher FPG (p = 0.001) and HbA1c (p = 0.00006) than individuals with ≤1 risk allele. Our findings suggest that lower plant protein intake may be a contributor to the increased ethnic susceptibility to diabetes described in Asian Indians. Randomised clinical trials with increased plant protein in the diets of this population are needed to see whether the reduction of diabetes risk occurs in individuals with prediabetes.

Download Full-text

Social inequalities in reception of social welfare support: A population based twin study

Norsk Epidemiologi ◽

10.5324/nje.v26i1-2.2016 ◽

2016 ◽

Vol 26 (1-2) ◽

Author(s):

Eivind Ystrom ◽

Ragnhild Ørstavik ◽

Ted Reichborn-Kjennerud ◽

Fartein Ask Torvik

Keyword(s):

Risk Factors ◽

Social Welfare ◽

Genetic Factors ◽

Social Inequalities ◽

Familial Risk ◽

Population Based ◽

Drop Out ◽

Historical Event ◽

Relative Contribution ◽

Specific Risk

Social welfare support runs in families. Recent studies using Nordic registry data have found individual differences in genetic factors to be of substantial importance for medical benefits. However, to date there has been no genetically informative studies on receiving social welfare support. To prevent young adults to not drop out of the work life and become recipients of social welfare support, it is of substantial interest to clarify to what extent the familiarity of social welfare support is due to genetic or social differences between families. We used data from the Historical-Event Database on 7,698 Norwegian twins born 1967-1979 to estimate the relative contribution of genetic factors, the effective familial environment (i.e. the “shared environment”), and individual-specific environmental factors. We found that the two forms of familial risk, genetic and shared environmental, explained 39% and 45%, respectively, of the risk for receiving social welfare support among young Norwegian twins. Only 17% of the variance in risk factors could be explained by individual-specific risk factors. It appears that risk for receiving social welfare support can to a great extent be explained by environmental differences between families. Therefore prevention strategies targeting social inequalities between families would indeed be effective. Furthermore, genetic risk factors are also important in explaining risk for receiving social welfare support. These effects could be mediated through heritable traits related to substance abuse, psychiatric disorders, and personality. Individual-specific risk factors were of very little importance. Hence, with regard to receiving social welfare support, family matters.

Download Full-text