Proposal summaries
B1253 - CNVs and psychosis-related neurodevelopmental phenotypes - 06/10/2011
There is strong evidence that rare copy number variants (CNVs) are associated with increased risk of schizophrenia (1-4) and autism (4-7), and a number of lines of evidence point to a shared genetic component to schizophrenia and autistic spectrum disorders. Aims: 1) To examine the frequency of CNVs within a population-based birth cohort. 2) To examine whether individuals with large/rare CNVs are at increased risk of developing autistic traits during childhood. 3) To examine whether individuals with large/rare CNVs show reduced cognitive ability during childhood and adolescence. 4)To examine whether individuals with large/rare CNVs are at increased risk of developing psychotic experiences during adolescence, and whether this association if present is mediated through autistic traits or impaired neurocognitive or social cognitive ability.
Hypotheses: We hypothesise that psychotic experiences, autistic traits, and impaired cognitive function will be more common in individuals with large, rare CNVs. We hypothesise that some CNVs will be shared across all neurodevelopmental outcomes (eg deletions in NRXN1), whilst others will show unique associations with these phenotypes. We hypothesise that autistic traits and impaired cognitive ability are unlikely to mediate any association between CNV burden and psychosis.
Outcomes: 1) Psychotic experiences at age 17 (definite psychotic experiences, and clinical/prodromal states). 2) Autistic traits. 3) Cognitive function.
B1252 - Ophthalmic associations of Developmental Co-ordination Disorder - 06/10/2011
Is the prevalence of the following conditions increased in children aged 7 who concurrently meet the DSM-IV criteria for DCD, compared to those who do not?
a.Reduced stereoacuity
b.Best eye visual acuity 6/18 or worse
c.Abnormal motor and sensory fusion at near or distance
d.Strabismus
e.Refractive error
f.Inter-ocular difference in acuity or refraction
g.Decreased visuo-spatial ability (according to maternal questionnaire at age 13). The answers to these will inform clinically important questions such as:
If a patient is diagnosed with DCD is there an indication for referring them routinely to either an ophthalmologist or an orthoptist?
In any given patient with DCD what is the likelihood of them having one of the above ophthalmic conditions?
Could any of the ocular problems listed in question 1 be used as a risk marker for DCD?
Methods: The primary exposure variable will be the presence of DCD according to the DSM-IV criteria at age 7 Cross-tabulations, then Univariate and Multivariable linear regression or logistic regression models will be used to look at the associations between DCD and the listed ocular abnormalities accounting for potential confounding and mediating factors identified from the literature. Adjustment will be made for the bias introduced by missing data using multiple imputation by chained equation.
B1249 - Engagement Science - 75th Anniversary Awards - 27/09/2011
A project team of administrative and research staff will invite our stakeholders to tell us in words/images what ALSPAC means to them. It could be a midwife's account of delivering one of the first babies, a participant's full-body scan or a researcher recalling their first major breakthrough using our data. This collection will be uploaded to a website and curated by a local artist who will use the material to create an artwork, which we will present to the local community at an event this autumn and at future events in 2012 when we celebrate our 21st birthday year.
B1246 - Dietary patterns in infancy and their associations with growth - 22/09/2011
We aim to examine dietary patterns obtained through Principal Components Analysis (PCA) from diet diary data collected at 8, 18 and 43 months and determine how these patterns relate to each other over time from infancy to the preschool period. We will examine associations between these dietary patterns and nutrient intakes and various familial socioeconomic and lifestyle factors. We will determine whether the early dietary patterns are related to rapid early weight gain, which has been shown to be associated with higher body fatness in these children at 5 years of age (Ong et al, 2000)
Research questions: We will use the diet diary data collected in ALSPAC at 8, 18 and 43 months (n ~ 800 with complete data) to:
1.Establish dietary patterns using PCA;
2.Examine associations between patterns and nutrients at each time point;
3.Examine associations between patterns and lifestyle factors at each time point;
4.Determine to what extent the patterns obtained over time are associated with each other;
5.Determine whether any particular pattern is associated with early rapid weight gain.
B1244 - Adolescent active and passive tobacco exposure and cardiometabolic health - 22/09/2011
The overall aim of this study is to examine the relationship between active and passive smoking and cardiometabolic risk factors (blood pressure, fasting glucose, insulin, lipids and inflammatory markers) in adolescence. Methods
The exposure variables are (a) serum cotinine levels in the ALSPAC YP (young person) assessed at teen-focus 3 (TF3; age 15-16 years); (b) self-reported smoking of YP at TF3; (c) self-report of the parents of the YP from their most recent (relative to TF3) questionnaire; we will also consider YP adiposity (BMI, waist and DXA fat mass) as an exposure for objective d and examine whether it interacts with smoking/cotinine in their associations with cardiometabolic outcomes or whether they combine independently
The outcome variables are systolic and diastolic blood pressure, fasting glucose, insulin, lipids and CRP in the YP assessed at TF3
We will consider the following as potential confounding factors: YP age, YP gender, YP pubertal status, maternal age at birth, maternal parity, head of household (parental) occupational social class, maternal and paternal education, ethnicity. YP adiposity will also be considered a potential confounding factor for objectives a-c and e but we will decide just how to model this after exploring the joint associations of this and smoking/cotinine with outocmes
B1243 - The Genetic Epidemiology of Atopic Dermatitis - 22/09/2011
Aim to address the current gaps in the knowledge of the genetic architecture of AD using a comprehensive programme of genetic epidemiological analysis, incorporating state-of-the-art technology and analysis methods, denser genetic information and better phenotype definitions, using existing collections of phenotype and genotype data. Identifying new genetic variants and biological pathways for AD and more fully characterising the genetic contribution of AD will improve the understanding of the underlying mechanisms involved in AD pathogenesis and identify targets for future drug discovery.
Objectives include: Refine the phenotype definition of AD using latent class analysis in ALSPAC, Carry out a large-scale genome-wide association (GWA) meta-analysis including analysis using improved AD definitions and subtypes, Refine existing signals and investigate the role of lower frequency variants in AD using next-generation sequence (NGS) data, Investigate parent-of-origin effects in AD using multi-generational data, Quantify the overall contribution made by common genetic variants to AD susceptibility & identify important pathways, Investigate 'geneXgene' (GxG) and 'geneXenvironment' (GxE) interactions in AD, Functional follow-up of AD associated variants.
B1247 - Does high protein intake in infancy associate with rapid growth beyond infancy - 22/09/2011
We aim to investigate protein intakes and dietary sources of protein at 8 months of age and relate these to growth trajectories up to 10 years. In addition we will assess the tracking of protein throughout childhood
Research questions: We will use the diet diary data collected in ALSPAC at 8 months (n greater than 1100) to calculate protein intake and assign infants to quintiles of protein intake. Within these quintiles we will evaluate:
1 What are the sources of protein in the diets of eight-month-olds?
2 Does high protein intake track though childhood?
3 Is high protein intake within the context of the whole diet associated with more rapid growth during infancy?
4 Is there any difference in rates of growth between quintiles of protein intake into later childhood?
Outcome measures: Weight, height and BMI through out infancy and childhood.
B1241 - Migraine GWAS meta-analysis - 16/09/2011
Aims: Migraine is the most common cause of chronic episodic severe headache, and affects 15% of the adult population with considerable burden to individuals and society. Although heritability is estimated to 50-60%, it was not until 2010 that the first genetic variant associated to the common forms of migraine was reported from a genome-wide association study (GWAS) of migraine with aura (Anttila et al, Nat. Genet., 2010). Since then one more GWAS of migraine has been published (Chasman et al, Nat. Genet., 2011), identifying three additional loci. Through this collaborative effort to perform a large-scale meta-analysis of GWAS data for migraine, our main aim is to detect (identify) the genetic mechanisms that underlie migraine. Specific aims include identifying common genetic variants that predispose to the development of migraine and its subtypes (migraine with aura, migraine without aura), as well as several follow-up analyses (see the attached analysis plan).
Hypotheses: We hypothesize that both common and low-frequency variants in the human genome contribute to the susceptibility for migraine, and that a high resolution meta-analysis of GWAS data can identify regions which contain sequence variants predisposing to the trait.
Exposure variables: Genetic variants as identified by GWAS genotyping.
Outcome variables: Presence of self-reported migraine (as identified by answers to questionnaire).
B1242 - Towards early intervention Does maternal behaviour mediate the independent association between antenatal depression and poor child emotional and behavioural outcomes - 15/09/2011
AIMS
The study aims to combine observed and maternal report data gathered as part of ALSPAC to investigate; The independent association between antenatal depression and multiple dimensions of maternal behaviour from 4 weeks to 5 years, whether this association mediates the independent impact of antenatal depression on later emotional/behavioural problems in the child.
B1240 - Reliability of parental recall of speech and language concerns in their child - 15/09/2011
As delayed speech is one area where retrospective reports have been utilised, we seek to compare contemporaneous and retrospective parental accounts of concerns over speech difficulties in preschool children. Comparing original accounts of child behaviour to retrospective accounts is the most powerful design for examining the reliability of retrospective recall.
Hypothesis: That for a child treated with speech and language therapy, or an official intervention, a mother would be more likely to recall concerns from the early years, that had not been reported at the time. That if the child has not had S & L therapy or intervention, mothers will be more likely to 'forget' their initial concerns. In general, we expect that mother's recall will be systematically biased by such an intervention.
Method: Secondary analysis to cross compare contemporaneous reports about worries regarding speech development measured when the study children were age between 18 and 30 months, with retrospective reports concerning whether mothers had had worries about children's speech development when in their early years. The retrospectively recalled worries were reported ten years later. We will determine whether the children had ever had any speech therapy or educational intervention and see if this is correlated with accuracy of recall.
Independent variable:SEN provision and intervention (therapy) , Outcome:Difference between contemporaneous and rerospective recall.
B1239 - Association between parental ages and offspring DNA methylation levels - 08/09/2011
Some findings suggest that offspring of older parents are at an increased risk of various disorders, such as cancer, diabetes type 1, obsessive-compulsive disorder, autism, schizophrenia, and bipolar disorder. The role of epigenetics in these associations is beginning to be explored. The most robust and readily measured epigenetic modification is DNA methylation, which is a normal and mitotically heritable change that regulates gene activity in the absence of underlying changes to DNA sequences. Epigenetic analysis may provide new insights into the mechanisms through which genetic and environmental factors jointly contribute to shape risk profiles. Exploiting differences in levels of DNA methylation and also genetic variants correlated with methylation levels according to parental age might contribute to our understanding of the extent to which associations between parental age and offspring health-related outcomes are explained by socioeconomic or biological factors. Aims and objectives: The overall aim is to examine the association of parental age with offspring DNA methylation levels. Specific objectives are: 1.) Examine the association of maternal and paternal age with offspring DNA methylation patterns. 2.) Compare the association of maternal age and offspring DNA methylation with that of paternal age with offspring DNA methylation. 3.) Examine genetic variation around any methylated sites that are related to parental age to identify genetic variation that might be causally related to that methylation. 4.) If associations are found between maternal / paternal age with offspring DNA methylation we would then explore whether this mediates associations with adverse offspring health outcomes; this would involve standard association analyses methods and also (if possible) genetical genomics approaches.
B1238 - A candidate gene approach for identifying genetic factors associated with height growth velocity in children - 08/09/2011
Our primary GWAS study, titled the Singapore Cohort Study of the Risk Factors of Myopia (SCORM), is an extension of the longitudinal survey of 2,000 children that were recruited from the age of 7 years old, and followed up annually until they reached 12 years old. The GWAS data along with longitudinal data on height and weight allow us to investigate the genetic etiology of growth characteristics. By investigating the rate of change of height across these 6 years, or the height growth gradient, we have identified several polymorphisms in growth related candidate genes with suggestive evidence (that beyond multiple testing) that are associated with height gradient.
Aim: To investigate the genetic etiology of height growth, which we believe will be partly or wholly distinct from the genetic etiology of height.
Hypothesis: Candidate genes for growth and appetite/hunger regulation may be associated with childhood growth characteristics.
Exposure variable: Genotypes from SNPs located in the candidate genes for growth and appetite/hunger regulation, after including a buffer region of 10kb on either flanks of each gene.
Outcome variable: Height growth, defined as the gradient of the regression line explaining height (y-axis) and age (x-axis).
Confounding variable: Gender of the child.
B1237 - Consortium of Adolescents Studies for the Genetics of Smoking and Nicotine Dependence CASGEN - 01/09/2011
We are interested in organizing a consortium of adolescent and young adult studies (up to age 24) to carry out a meta-analysis of genetic factors for nicotine dependence and cigarette smoking in adolescence. We are aware of several adolescent studies that have genetic and phenotypic data. However, each study is individually underpowered for genetic analysis. Were we able to accumulate a large enough number of such studies, we might be able to implement a meta-analysis similar to that carried out for adults by Saccone and her collaborators (PLoS Genetics 2010) or Ware and colleagues (SRNT 2011).
We are at an early stage of development - several of the relevant studies have extracted DNA but not conducted genotyping, while others have not even collected material for DNA extraction. An analytical plan has also not yet been developed. Nevertheless, we will follow established protocols (e.g., Saccone et al., 2010) for the meta-analysis of data from multiple cohorts. A protocol and statistical analysis code will be developed and implemented by each cohort. Raw data would not be required - coefficients generated by the analysis code would be sufficient.
The primary aim of this consortium is to elucidate genetic influences on cigarette smoking phenotypes in adolescence and young adulthood, specifically: 1) smoking initiation, and 2) subsequent progression to regular use.
B1248 - High Bone Mass Study - 01/09/2011
No outline provided as this is not a full proposal (just a request to use our facilities which has been approved).
B1235 - The antecedents and consequences of gambling behaviour in young people - 25/08/2011
The overall aims of the ALSPAC gambling study are to investigate the distribution and correlations of gambling in young people, and to describe the developmental trajectories from early childhood of young people with gambling problems.
Specific Objectives of the 20/21yr sweep:
1. To describe the gambling activity and the prevalence of gambling behaviours at 21 years, and their relation to parental gambling patterns.
2. To investigate the change in gambling behaviour between 17 and 21, and in particular to assess whether those 'at risk' at 17 have become problem gamblers at 21.
3. To describe the associations of problem gambling with other risk taking behaviours, alcohol and drug use from 17 to 21yrs.
4. To elucidate the interactions between gambling behaviour, impulsivity, sensation seeking and depression in young people.
B1234 - 1958 Management - 2011 onwards - 19/08/2011
This infrastructural project is targeted at strategic development of that component of the 1958 Birth Cohort
(1958BC) that is known as the "Biomedical Resource". It will ensure that optimum utility can be extracted
from the Resource during 2011-2014 and that the 1958BC will then be well placed to maintain and extend its
internationally hailed contribution to research in the biomedical and social sciences. The proposal subsumes
three complementary objectives: (1) secure the basic infrastructure as it now exists, thus ensuring that the
successful systems that have already been implemented can be maintained into the future; (2) enhance the
infrastructure from an administrative and strategic management perspective to ensure that it can face
expected and unexpected future challenges and opportunities both effectively and resiliently; (3) enhance the
infrastructure from a scientific perspective to ensure that both the 1958BC, and UK Bioscience, are best
placed to face the scientific challenges of the future. The new science underpinning this application is
focused entirely on optimising and enhancing the utility of the pre-existing Biomedical Resource - the
proposal contains no hypothesis-driven research and no funding is sought for additional data or sample
collection from study participants. The responsibility for strategic development of the cohort as a whole -
including planning for future data sweeps - will remain with the Centre for Longitudinal Studies (CLS). This
application reflects a considered evolution in the thinking of the funders (MRC, WT, ESRC) about strategic
development of the 1958BC Biomedical Resource and of the systems and policies governing access to it.
Initially, responsibility for access and strategic development lay with the Principal Investigators of the
original grant. But, it later became clear that if resource utility was to be optimised it should be managed and
developed by independent scientists and administrators. In 2008, responsibility for managing the 1958BC
biobank therefore transferred to ALSPAC laboratories at the University of Bristol under a joint grant from
MRC/WT. Then, in 2009, responsibility for oversight and strategic development of the Biomedical Resource
as a whole passed to the independent access committee chaired from the University of Leicester under
another small grant from MRC/WT. Following strategic discussions with MRC, WT and ESRC, the
University of Leicester and University of Bristol now outline a vision for joint management of the Biomedical
Resource, to include its strategic development as an infrastructure, under a grant requesting limited - but
adequate - funding to ensure sustainability.
B1225 - Genome-wide Interaction study on birth weight and Maternal Smoking - 18/08/2011
Maternal smoking during pregnancy is the most important modifiable risk factor for reduced birth size and reduces infant birth weight in a dose related manner (US Dept. of Health and Human Services, 2004). The precise biological routes by which exposure to smoking during pregnancy directly or indirectly influences fetal growth remain unknown. Few unreplicated candidate gene studies have suggested that the offspring's genotype can influence the sensitivity to the effects of maternal smoking (Infante-Rivard, et al., 2006; Price, et al., 2010). Genome-wide interaction studies are warranted and only meta-analysis across large cohorts can provide the sample size necessary for adequate statistical power. It will be vital to include as many cohorts as possible.
Heterogeneity in the exposure variable compromises meta-analytic studies of genotype-environment interaction (Palla et al., 2010). Therefore, we first focus on maternal smoking as a binary exposure as it can be measured reliably and consistently across studies. Dosage and timing are likely to be important modifiers and may be less well recorded. Thus, we will perform secondary analyses using these variables in cohorts where such information is available.
We propose a genome-wide meta-analysis of interactions between child genotype and maternal smoking on singleton infant birth weight adjusted for gestational age. The investigation will focus on term deliveries. Gestational age and gender are desirable covariates in the analysis.
B1233 - Investigating interdependencies in causal inference statistical methodology - 18/08/2011
Aims: We are pursuing methodological research on the concept of 'interdependencies' in causal inference.
Methods: The concept of an interdependency in causal inference is most similar to that of an interaction in standard statistical analysis. There are a series of papers by Vanderweele and Robins from 2007 onwards which define interdependence between causes to produce an effect, as opposed to statistical interaction. They also derive observable constraints to detect interdependence. Our work seeks to extend their constraints and defined interdependence without any deterministic assumptions, which they use with counterfactuals.
Example: In our example we would like to investigate whether there are interdepencies between adiposity genotypes on their effect on measures of adiposity such as BMI and waist-hip ratio. Specifically, the application investigates the interdependence between the FTO (X_1) and MC4R (X_2) SNPs in causing obesity (Y).
B1230 - Mendelian Randomization to understand the causal relationship between adiponectin and insulin resistance/related traits - 18/08/2011
Aim and hypothesis: We propose a project that follows on from the recent GWAS paper from the adipogen consortium, and the related paper led by the GSK team that resequenced the coding regions of the ADIPOQ gene.
We would like to use ADIPOQ genotypes to test the hypothesis that adiponectin causally influences insulin resistance, type 2 diabetes and related traits. We propose a Mendelian randomization approach. The proposal will build on the efforts reported in the main GWAS paper.
We plan to:
1. Use several SNPs in the ADIPOQ locus. These include those that are in partial LD, but that together explain more of the variance in circulating adiponectin levels - as replicated in several studies analysed by the proposers (RISC, CoLaus, WTDundee). We believe that there are at least 3 independent signals at ADIPOQ, captured by 3 or 4 SNPs. These signals are tagged to varying extents in different studies. One SNP in particular is a low frequency, large effect variant that will almost certainly require direct genotyping in most studies. Depending on the GWAS chip used and imputation quality, different studies will likely need to genotype 1-4 SNPs. Some of the critical SNPs are on metabochip.
2. Limit the study to ADIPOQ SNPs. We estimate that the ADIPOQ SNPs explain greater than 3% of the variance in adiponectin levels. With enough studies we should be well powered to perform instrumental variables approaches on traits strongly correlated to adiponectin levels, such as fasting and M value based measures of insulin resistance, and lipids. This approach will have the advantage that we are only dealing with "cis" effects - SNPs most likely only acting on circulating adiponectin levels directly through the encoding gene. We will therefore avoid uncertainties due to pleiotropic effects.
3. Limit the Mendelian randomization tests to only studies with all three sides of the "triangles" in place - SNPs, adiponectin and the "secondary" outcome phenotypes. This approach will allow us to perform the more formal "instrumental variables" approach to mendelian randomization. We have extensive experience performing these analyses and will draft an analysis plan.
4. for all studies involved perform a meta-analysis of instrumental variables based estimates of the correlation between adiponectin and secondary traits.
Exposure variable: genotype at 4 SNPs (please see ablove).
Primary outcome variable: adiponectin
Secondary outcome variables: T2D statuse, BMI, HDL, triglyceride, waist hip ratio, fasting insulin, fasting glucose
Confounding variables: age, gender, center (if applicable).
Requirements for participation:
1. ability to genotype 1-4 specific SNPs in study (or subset of study that has adiponectin and secondary outcomes measured) - small possibility that the rare SNP will be imputable but not currently possible with Affy6.0 chip and latest 1000G data.
2. SNPs, adiponectin and main secondary outcome measured in at least 500 individuals.
3. Highly preferable - access to STATA - the statistical software package that can implement instrumental variables analyses most readily.
B1228 - Genetics prices and addiction - 11/08/2011
An economics literature has examined several determinants of addiction to cigarettes, including family habits, prices and discount rates. One area which is currently underexplored within this setting is the role of genetics in addiction formation. Both prices (Gruber & Zinman, 2001) and genes (Ding et al, 2009; Fletcher & Lehrer, 2011) have been found to drive smoking behaviour, but the interaction has not been explored. Our project will investigate how individuals differ in their response to health policies based on prices, and how genetics play a role in this.
In stage one of the project, we hypothesise that two mechanisms interact to partially determine the habit formation of smoking and other drug taking for young ALSPAC members. Firstly, young individuals consider the price of cigarettes when deciding whether to smoke. We will exploit price changes along two dimensions. As cohort members age, changes in taxes on cigarettes vary the price. Additionally, the ALSPAC children were born across a 21 month period and consequently for a given age, the price of a cigarette will vary. This will allow us to identify the effect of price changes upon the first age of smoking.
Secondly, an individual's response to their first cigarette will depend among other things, upon their genotype. Variations in both the speed of nicotine metabolism and dopamine and serotonin transmitters create heterogeneous adverse or positive reactions of a first cigarette, and subsequent dependence. We will investigate whether the response to a price change is less effective in individuals with certain genotypes.
In the second phase of the project we will explore the implications for the ALSPAC children of forming an addiction. Nicotine, alcohol or cannabis can themselves have detrimental effects on individuals. Retrospective information on smoking habits, prices and genotype will be combined with outcomes for 16 year old children. We will explore the effect on behavioural outcomes, obesity, expectations for the future, achievement against test scores and criminal activity. The methodology will exploit genetic variations in an instrumental variable setting. Assuming that genotype drives child outcomes only through its effect on smoking dependence allows estimation of the causal effect of addiction.
There are important policy implications inherent in this study. If the responsiveness of drug dependence to price changes varies across genotype, a group of individuals will require stronger intervention methods than prices alone. This is particularly true if we find adverse effects of forming an addiction on later outcomes for children.
Variables
We plan to make use of the genetic information for mothers and children of ALSPAC. The gene CYP2A6 drives the metabolism of nicotine and cotinine as well as other drugs and toxins.[1] There are different variants of activity of CYP2A6, and ALSPAC contains data on two in particular - CYP2A6*2 and CYP2A6*9 - which indicate slow functionality. CYP2A6*2 and CYP2A6*9 was measured for children and mothers. Lerman & Berrettial (2003) note the importance to control for maternal genes in order to separate the effects from the child's inherited genotype and familial smoking behaviour which is driven by parental genes. We would therefore request the genotype data for both generations. We hypothesise that children with differing activity of the gene will have different responses to smoking the first cigarette, and subsequent development of a smoking habit. Smoking is indeed found less likely in individuals with these variants and, for those who do smoke, quantities reported are lower[2]. Also, through its metabolism of other toxins, variants of CYP2A6 may drive the response to other drugs including alcohol and cannabis.
In addition, two genes contained in the ALSPAC genotyping archive which link to dopamine and serotonin transmitters are
SLC6A4 (5HTT) and MAOA. Variants in these genes lead to differential signals of pleasure upon consuming drugs, which again may drive the early stage addiction and dependence to the drugs.
At ages 14 and 16 questionnaires recorded the age ALSPAC children first smoked, drank an alcoholic drink and took drugs, the intensity with which they consumed them and records how the drugs affected them. For example, there is information on whether they felt ill after smoking. We will explore whether the reaction to the first experience of a drug differs by genotype.
The confounding variables are grouped into several categories. We will control for family smoking habits through the history of maternal and partner's reported smoking status. This will be important to the extent that children mimic the smoking behaviour of their parents. Additionally, as smoking behaviour is non-random across socio-economic groups we will control for education and occupation of parents. It is a concern that smoking behaviour is indicative of discount rates, whereby individuals with high discount rates place little weight on future periods relative to the present. To control for this, we will utilise the variables on diet, fitness and gambling.
[1]Hughes et al (1984), Ingelman-Sundberg, Nakajima M, Yamamoto T, Nunoya K, et al.(1996), Messina ES et al (1997), Benowitz NL, Jacob P III (1994).
[2] Schoedel et al (2004).