Population Attributable Risk Fraction Research Articles

Gastroenteritis in a Taipei emergency department: aetiology and risk factors

A matched case-control study was used to determine pathogens and risk factors associated with gastroenteritis in a Taipei Emergency Department. Viruses (40.0%) were the leading cause of gastroenteritis, with noroviruses the most prevalent (33.2%). Bacteria were found in 26.0% of all cases, mostly suspected diarrheagenic E. coli (22.2%), followed by Salmonella spp. (5.4%) and Vibrio parahaemolyticus (4.2%). Giardia lamblia was identified in 16.4% of all cases. Statistical significance was noted for seven risk factors: taking antacids before gastroenteritis (OR = 3.91; 95% CI, 2.13, 7.15), other household members with gastroenteritis (OR = 5.18; 95% CI, 2.09, 12.85), attending a banquet (OR = 1.93; 95% CI, 1.25, 2.98), eating out (OR = 2.35; 95% CI, 1.30, 4.23), drinking bottled water (OR = 1.72; 95% CI, 1.07, 2.75), eating honey peaches (OR = 3.26; 95% CI, 1.24, 8.58), and eating raw oysters (OR = 3.24; 95% CI, 1.02, 10.28). Eating out was identified as the highest risk behavior, as measured by population attributable risk fraction (PAR) (50.9%). Respective PAR values for drinking bottled water, attending a banquet and taking antacids before illness were 19.7%, 19.6% and 17.6%. Of these, additional research on bottled water appears to be the highest priority, because this is the first time it has been identified as a risk factor for gastroenteritis.

Cardiovascular risk and all-cause mortality attributable to diabetes: Tehran lipid and glucose study.

To quantify the burden of cardiovascular diseases (CVD), and all-cause mortality attributable to diabetes. Data on an 8.6-yr follow-up of 6331 participants (2741 men), free of CVD at baseline, were analyzed to determine the burden of CVD and all-cause mortality attributable to self-reported and screen-detected diabetes mellitus (SRDM and SDDM, respectively). Risks of events of interest were separately assessed for women and men using Cox-proportional-hazard model. The mean age at baseline was 47 yr with 997 (15.7%) of participants having diabetes (men 14.8%, women 16.5%). SRDM and SDDM prevailed in 9.7% (men 9.2, women 10.2%) and 6.0% of participants (men 5.7, women 6.3%), respectively. During follow up (52,404 person-yr), we observed 447 incident cases of CVD [387 had coronary heart disease (CHD)] and 209 deaths. Among men, participants with SDDM had increased relative hazard for all-cause mortality translated to a population attributable risk fraction (PAF) of 10.1%. Among women, SDDM was associated with CVD and CHD but not with all-cause mortality; so that 9.3% and 8.8% of CVD and CHD events were respectively attributable to the SDDM. If SRDM had been eliminated from the population, the incidences of CVD, CHD, and death would have decreased by 10.5, 9.5, and 17.3% in men; and 22.0, 24.2, and 17.8% in women, respectively. SDDM and SRDM have high PAF for all-cause mortality and CVD. Besides diabetes treatment and prevention, screening to detect undiagnosed diabetes should warrant high priority among the public health strategies to lower the incidence of CVD and mortality.

The eczema risk variant on chromosome 11q13 (rs7927894) in the population-based ALSPAC cohort: a novel susceptibility factor for asthma and hay fever

In a genome-wide association study, a common variant on chromosome 11q13.5 (rs7927894[T]) has been identified as a susceptibility locus for eczema. We aimed to analyze the effect of this risk variant on asthma and hay fever and to determine its impact on the general population level in over 9300 individuals of the prospectively evaluated Avon Longitudinal Study of Parents and Children birth cohort. We demonstrate an association of rs7927894[T] with atopic asthma and with hay fever. The largest effect sizes were found in patients with the combined phenotype atopic asthma plus eczema [odds ratio (OR) = 1.50; 95% confidence interval (CI) 1.20-1.88; P = 3.7 × 10(-4)] and hay fever plus eczema (OR = 1.37; 95% CI 1.15-1.62; P = 3.8 × 10(-4)). We replicated the effects of rs7927894[T] on eczema-associated asthma and hay fever independently in the German GENUFAD (GEnetic studies in NUclear Families with Atopic Dermatitis) study and show that they are significantly larger than the effect observed in eczema. The estimated population attributable risk fractions for eczema, eczema-associated atopic asthma or hay fever were 9.3, 24.9 and 23.5%, respectively. Finally in eczema, we found a synergistic interaction of rs7927894[T] with filaggrin gene (FLG) mutations, which are a major cause of epidermal barrier dysfunction, and replicated the interaction in the German Multicenter Allergy Study birth cohort. The synergistic effect of rs7927894[T] and FLG mutations on eczema risk as well as the association of both variants with eczema-associated atopic asthma and hay fever point to an involvement of rs7927894[T] in a functional pathway that is linked to the barrier defect.

Relationship of moderate metabolic risk factor clustering to cardiovascular disease mortality in non-lean Japanese: A 15-year follow-up of NIPPON DATA90

ObjectiveThe individual components of metabolic syndrome are defined as levels ranging from moderate to high level as to require medication. We investigated the impact of moderate metabolic risk factor clustering on cardiovascular disease (CVD) mortality. MethodsWe followed up 6758 non-lean Japanese in randomly selected areas from all over the country who had no history of CVD for 15 years. The multivariate-adjusted hazards ratio (HR) and 95% confidence interval (CI) for CVD mortality according to the number of moderate metabolic risk factors (BMI≥25kg/m2, 130/85mmHg≤systolic/diastolic BP<140/90mmHg, 140mg/dl≤casual blood glucose<200mg/dl, triglycerides≥150mg/dl and/or HDL cholesterol<40mg/dl [men], 50mg/dl [women]) were estimated using the Cox proportional hazards model. The population-attributable risk fraction of moderate metabolic risk factor clustering was also estimated. ResultsDuring the follow-up, 282 participants died of CVD. CVD mortality tended to increase with the number of moderate metabolic risk factors. However, they were not statistically significant. The multivariate-adjusted HRs were 1.82 (95%CI: 0.89–3.73) for having any moderate metabolic risk factors and 2.87 (95%CI: 1.46–5.64) for having any medication-required metabolic risk factors, compared with participants without any moderate metabolic risk factors. The population-attributable risk fractions were 7.3% and 52.4% for any moderate and medication-required metabolic risk factors, respectively. ConclusionsWe did not find the statistically significant increase of CVD mortality for moderate metabolic risk factor clustering. Its attribution was relatively small in this Japanese population. More efforts would be required to detect and control medication-required risk factors.

Periodontal disease and some adverse perinatal outcomes in a cohort of low risk pregnant women

ObjectiveTo evaluate the association of periodontal disease (PD) in pregnancy with some adverse perinatal outcomes.MethodThis cohort study included 327 pregnant women divided in groups with or without PD. Indexes of plaque and gingival bleeding on probing, probing pocket depth, clinical attachment level and gingival recession were evaluated at one periodontal examination below 32 weeks of gestation. The rates of preterm birth (PTB), low birth weight (LBW), small for gestational age (SGA) neonates and prelabor rupture of membranes (PROM) were evaluated using Risk Ratios (95%CI) and Population Attributable Risk Fractions.ResultsPD was associated with a higher risk of PTB (RRadj. 3.47 95%CI 1.62-7.43), LBW (RRadj. 2.93 95%CI 1.36-6.34) and PROM (RRadj. 2.48 95%CI 1.35-4.56), but not with SGA neonates (RR 2.38 95%CI 0.93 - 6.10).ConclusionsPD was a risk factor for PT, LBW and PROM among Brazilian low risk pregnant women.

Population Attributable Risk Fraction for Selected Chronic Diseases in India

India's current health transition stage poses a critical challenge of dealing with the unfinished agenda of communicable diseases and the steadily rising burden of noncommunicable diseases. A significant burden of chronic diseases in India is attributable to household and individual level health risk factors coupled with socioeconomic conditions. From this perspective, this article made a first time effort to assess disease burden attributable to health risk factors using cross-sectional population health survey data. Population attributable fractions (PAF) were estimated for a cluster of health risk factors that include unsafe water, lack of sanitation, exposure to cooking smoke, tobacco and alcohol use, physical inactivity, and socioeconomic conditions on a set of widely prevalent chronic diseases such as tuberculosis, malaria, diarrhea, diabetes, angina, and asthma. Data from the 2003 World Health Survey was used. The analysis revealed evidence of a significant contribution of health risk factors to India's escalating chronic disease burden. The contribution of health risk factors toward chronic disease burden varied by residence. Results suggest that promotional health care based policies to deal with health risks should be a major priority in policy agenda to combat with the challenge of emerging noncommunicable disease coupled with the persistent burden of communicable diseases. Disease burden in India could be halved by effectively modifying exposure to the risk factors through promotional health care.

Prevention Potential of Risk Factors for Childhood Overweight

Background: In order to better target prevention initiatives for the obesity epidemic in Canada, policy-makers, in addition to information about risk factors, require an understanding of the preventive potential which is best provided by the risk factor’s population attributable risk fraction (PARF). Objective: To estimate the PARF for childhood overweight risk factors as identified by a population-based study of elementary schoolchildren in Nova Scotia. Methods: Population-based survey data of Grade 5 students who participated in the 2003 Children’s Lifestyle and School Performance Study in Nova Scotia, Canada, were linked to a provincial perinatal registry. PARFs were calculated from a parsimonious multilevel logistic regression model. Results: Physical activity, sedentary activity, maternal smoking during pregnancy, and maternal pre-pregnancy weight were considered potentially preventable. Sedentary activity (as estimated from time spent viewing TV, computers and video games or “screen time”) and maternal pre-pregnancy weight appeared to offer the greatest potential for prevention. In total, approximately 40% of overweight in childhood could potentially be prevented. Conclusion: Excess screen time and maternal pre-pregnancy weight offer the greatest potential for prevention of childhood overweight at 11 years of age. Key words: Obesity; child; prevention; population attributable risk; public health; physical activity; nutrition

Translating the epidemiology of psychosis into public mental health: evidence, challenges and future prospects

Genetic and environmental factors are associated with psychosis risk, but the latter present more tangible markers for prevention. We conducted a theoretical exercise to estimate the proportion of psychotic illnesses that could be prevented if we could identify and remove all factors that lead to increased incidence associated with ethnic minority status and urbanicity. Measures of impact by population density and ethnicity were estimated from incidence rate ratios [IRR] obtained from two methodologically-similar first episode psychosis studies in four UK centres. Multilevel Poisson regression was used to estimate IRR, controlling for confounders. Population attributable risk fractions [PAR] were estimated for our study population and the population of England. We considered three outcomes; all clinically relevant ICD-10 psychotic illnesses [F10-39], non-affective psychoses [F20-29] and affective psychoses [F30-39]. One thousand and twenty-nine subjects, aged 18-64, were identified over 2.4 million person-years. Up to 22% of all psychoses in England (46.9% within our study areas) could be prevented if exposures associated with increased incidence in ethnic minority populations could be removed; this is equivalent to 66.9% within ethnic minority groups themselves. For non-affective psychoses only, PAR for population density was large and significant (27.5%); joint PAR with ethnicity was 61.7%. Effect sizes for common socio-environmental risk indicators for psychosis are large; inequalities were marked. This analysis demonstrates potential importance in another light: we need to move beyond current epidemiological approaches to elucidate exact socio-environmental factors that underpin urbanicity and ethnic minority status as markers of increased risk by incorporating gene-environment interactions that adopt a multi disciplinary perspective.

Predictors of mortality among elderly people living in a south Indian urban community; a 10/66 Dementia Research Group prospective population-based cohort study

BackgroundEighty percent of deaths occur in low and middle income countries (LMIC), where chronic diseases are the leading cause. Most of these deaths are of older people, but there is little information on the extent, pattern and predictors of their mortality. We studied these among people aged 65 years and over living in urban catchment areas in Chennai, south India.MethodsIn a prospective population cohort study, 1005 participants were followed-up after three years. Baseline assessment included sociodemographic and socioeconomic characteristics, health behaviours, physical, mental and cognitive disorders, disability and subjective global health.ResultsAt follow-up, 257 (25.6%) were not traced. Baseline characteristics were similar to the 748 whose vital status was ascertained; 154 (20.6%) had died. The mortality rate was 92.5/1000 per annum for men and 51.0/1000 per annum for women. Adjusting for age and sex, mortality was associated with older age, male sex, having no friends, physical inactivity, smaller arm circumference, dementia, depression, poor self-rated health and disability. A parsimonious model included, in order of aetiologic force, male sex, smaller arm circumference, age, disability, and dementia. The total population attributable risk fraction was 0.90.ConclusionA balanced approach to prevention of chronic disease deaths requires some attention to proximal risk factors in older people. Smoking and obesity seem much less relevant than in younger people. Undernutrition is preventable. While dementia makes the largest contribution to disability and dependency, comorbidity is the rule, and more attention should be given to the chronic care needs of those affected, and their carers.

Impact of hearing difficulty on dependence in activities of daily living (ADL) and mortality: A 3-year cohort study of community-dwelling Japanese older adults

Studies have associated hearing impairment with adverse health outcomes, but the actual impact of hearing difficulty has been barely investigated. We investigated among older adults (i) the prevalence of hearing difficulty, (ii) the association of hearing difficulty with a composite outcome of dependence in activities of daily living (ADL) and death, and (iii) the population attributable risk fraction (PAF) of hearing difficulty. In 2005, a home-visit survey of 1364 Japanese older adults aged ≥65 (participation proportion = 95.5%) was conducted to evaluate self-reports of hearing difficulty. Over 3 years, 99.4% of the initial sample was followed. Outcomes were measured by incidence of death or dependence in ADL. In the sample, the prevalence of hearing difficulty was 17.7% (age ≥65) and 25.7% (age ≥75). Hearing difficulty at high levels was associated with a composite outcome of dependence in ADL and mortality (adjusted odds ratio = OR and 95% confidence interval = 95% CI = 6.19 (1.92–19.92)) as well as with each outcome independently. Improving the hearing difficulty from high to moderate or no difficulty would reduce the composite outcome in 4.3% (age ≥65) and in 6.3% (age ≥75) of the target population. In conclusion, hearing difficulty was common, was associated with and had substantial impact on adverse health outcomes.

Relative Benefits of Population-Level Interventions Targeting Restraint-Use in Child Car Passengers

Because public health resources for injury prevention are limited, methods for comparing competing strategies are needed. We aimed to estimate potential injury reductions for 4 population-level interventions that target restraint practices for child car passengers aged 0 to 12 years. Population-attributable risk fraction (PARF) is a population-level estimate of excess risk from exposure to a risk factor. PARFs were calculated for each intervention scenario by using published age-specific mortality/injury relative-risk estimates; restraint practices among injured child car passengers from police-collected data; and observational data for correctness of restraint use in New South Wales, Australia. PARF reductions were estimated for population uptakes of 25%, 50%, and 75%. Assuming a 50% population uptake, (1) promoting age-appropriate restraint use could prevent additional fatalities (5.1%, infants; 3.4%, 1- to 6-year-olds) and nonfatal injuries (3.2%, infants; 16.2%, 1- to 6-year-olds) compared with promoting any restraint use; (2) further encouraging correct age-appropriate restraint use could also prevent additional fatalities (9.1%, infants; 14.3%, 1- to 6-year-olds) and nonfatal injuries (9.2%, infants; 10.7%, 1- to 6-year-olds); and (3) for children aged 7 to 12 years, promoting correct use of restraints could prevent an additional 3.4% fatalities and 3.1% nonfatal injuries compared with promoting any restraint use. Interventions that target child passenger-restraint practices offer population-level benefits in terms of reduction in fatalities and injuries. These tangible benefits call for action internationally, not only to promote restraint use but correct age-appropriate restraint use for child car passengers.

Diet, Screen Time, Physical Activity, and Childhood Overweight in the General Population and in High Risk Subgroups: Prospective Analyses in the PIAMA Birth Cohort

Objective. To prospectively identify behavioral risk factors for childhood overweight and to assess their relevance in high risk sub groups (children of mothers with overweight or low education). Methods. In the PIAMA birth cohort (n = 3963), questionnaire data were obtained at ages 5 and 7 on “screen time”, walking or cycling to school, playing outside, sports club membership, fast food consumption, snack consumption and soft drink consumption. Weight and height were measured at age 8 years. Results. Screen time, but none of the other hypothesized behavioral factors, was associated with overweight (aOR 1.4 (CI: 1.2–1.6)). The adjusted population attributable risk fraction for screen time > 1 hr/day was 10% in the high risk and 17% in the low risk sub groups. Conclusion. Reduction of screen time to < 1 hr/day could result in a reduction of overweight prevalence in the order of 2 percentage points in both high and low risks sub groups.

Evaluation of population impact of candidate polymorphisms for coronary heart disease in the Framingham Heart Study Offspring Cohort

In order to evaluate the population impact of putative causal genetic variants over the life course of disease, we extended the static estimation of population-attributable risk fraction and developed a novel tool to evaluate how the population impact changes over time using the Framingham Heart Study Offspring Cohort data provided to the Genetic Analysis Workshop 16, Problem 2. A set of population-attributable risk fractions based on survival functions were estimated under the proportional hazards models. The development of this novel measure of population impact creates a more comprehensive estimate of population impact over the life course of disease, which may help us to better understand genetic susceptibility at the population level.

The Struggle to Prevent and Evaluate: Application of Population Attributable Risk and Preventive Fraction to Suicide Prevention Researach

Population attributable risk (PAR) estimates have been used in suicide research to evaluate the impact of psychosocial and socioeconomic risk factors, including affective disorders, traumatic life events, and unemployment. A parallel concept of preventive fraction (PF), allowing for estimation of the impact of protective factors and effectiveness of preventive interventions, is practically unknown in suicidology. The study authors discuss the application of both concepts to suicide research and prevention, and review literature on the subject. Despite several methodological and conceptual limitations, both PAR and PF are valuable instruments to inform development and evaluation of suicide prevention programs.

Suicide Attempts, Gender, and Sexual Abuse: Data From the 2000 British Psychiatric Morbidity Survey

The purpose of this study was to utilize data from the 2000 British National Survey of Psychiatric Morbidity, a randomized cross-sectional survey of the British population that included questions relating to the phenomena of suicidality and sexual abuse, to test the hypothesis that suicide attempts in women are significantly associated with a history of sexual abuse. Participants were male and female volunteers, ages 16 to 74 years old (N=8,580), interviewed in the 2000 British National Survey of Psychiatric Morbidity. Sexual abuse was strongly associated with a history of suicide attempts as well as of suicidal intent and was more common in women. The population attributable risk fraction was considerably greater in female respondents (28%) than in male respondents (7%), which is consistent with more prevalent exposure to sexual abuse among women. The effect of sexual abuse on suicidal attempts and suicidal intent was reduced by controlling for affective symptoms, suggesting that the effect of the former was likely to be mediated by affective changes. Sexual abuse is a significant antecedent of suicidal behavior, particularly among women. In identifying suicidal behavior, it is important to consider the possibility of sexual abuse, since it implies a need for focused treatment.

Estimating the incidence of lung cancer attributable to occupational exposure in Iran.

ObjectiveThe aim of this study was to estimate the fraction of lung cancer incidence in Iran attributed to occupational exposures to the well-established lung cancer carcinogens, including silica, cadmium, nickel, arsenic, chromium, diesel fumes, beryllium, and asbestos.MethodsNationwide exposure to each of the mentioned carcinogens was estimated using workforce data from the Iranian population census of 1995, available from the International Labor Organization (ILO) website. The prevalence of exposure to carcinogens in each industry was estimated using exposure data from the CAREX (CARcinogen EXposure) database, an international occupational carcinogen information system kept and maintained by the European Union. The magnitude of the relative risk of lung cancer for each carcinogen was estimated from local and international literature. Using the Levin modified population attributable risk (incidence) fraction, lung cancer incidence (as estimated by the Tehran Population-Based Cancer Registry) attributable to workplace exposure to carcinogens was estimated.ResultsThe total workforce in Iran according to the 1995 census identified 12,488,020 men and 677,469 women. Agriculture is the largest sector with 25% of the male and 0.27% of female workforce. After applying the CAREX exposure estimate to each sector, the proportion exposed to lung carcinogens was 0.08% for male workers and 0.02% for female workers. Estimating a relative risk of 1.9 (95% CI of 1.7–2.1) for high exposure and 1.3 (95% CI 1.2–1.4) for low exposure, and employing the Levin modified formula, the fraction of lung cancer attributed to carcinogens in the workplace was 1.5% (95% CI of 1.2–1.9) for females and 12% (95% CI of 10–15) for males. These fractions correspond to an estimated incidence of 1.3 and 0.08 cases of lung cancer per 100,000 population for males and females, respectively.ConclusionThe incidence of lung cancer due to occupational exposure is low in Iran and, as in other countries, more lung cancer is due to occupational exposure among males than females.

Resuscitation at birth and cognition at 8 years of age: a cohort study

SummaryBackgroundMild cerebral injury might cause subtle defects in cognitive function that are only detectable as the child grows older. Our aim was to determine whether infants receiving resuscitation after birth, but with no symptoms of encephalopathy, have reduced intelligence quotient (IQ) scores in childhood.MethodsThree groups of infants were selected from the Avon Longitudinal Study of Parents and Children: infants who were resuscitated at birth but were asymptomatic for encephalopathy and had no further neonatal care (n=815), those who were resuscitated and had neonatal care for symptoms of encephalopathy (n=58), and the reference group who were not resuscitated, were asymptomatic for encephalopathy, and had no further neonatal care (n=10 609). Cognitive function was assessed at a mean age of 8·6 years (SD 0·33); a low IQ score was defined as less than 80. IQ scores were obtained for 5953 children with a shortened version of the Weschler intelligence scale for children (WISC-III), the remaining 5529 were non-responders. All children did not complete all parts of the test, and therefore multiplied IQ values comparable to the full-scale test were only available for 5887 children. Results were adjusted for clinical and social covariates. Chained equations were used to impute missing values of covariates.FindingsIn the main analysis at 8 years of age (n=5887), increased risk of a low IQ score was recorded in both resuscitated infants asymptomatic for encephalopathy (odds ratio 1·65 [95% CI 1·13–2·43]) and those with symptoms of encephalopathy (6·22 [1·57–24·65]). However, the population of asymptomatic infants was larger than that of infants with encephalopathy, and therefore the population attributable risk fraction for an IQ score that might be attributable to the need for resuscitation at birth was 3·4% (95% CI 0·5–6·3) for asymptomatic infants and 1·2% (0·2–2·2) for those who developed encephalopathy.InterpretationInfants who were resuscitated had increased risk of a low IQ score, even if they remained healthy during the neonatal period. Resuscitated infants asymptomatic for encephalopathy might result in a larger proportion of adults with low IQs than do those who develop neurological symptoms consistent with encephalopathy.FundingWellcome Trust.

Genetic polymorphisms of the angiotensin II type 1 receptor gene and diastolic heart failure

The aim of the study was to investigate the association between angiotensin II type 1 receptor (AGTR1) gene polymorphisms and diastolic heart failure (DHF) in a case controlled study. Of 1752 consecutive patients analyzed, 176 diagnosed with DHF and confirmed by echocardiography were recruited. Controls were matched one-to-one by age, sex, hypertension, diabetes, renal function, and medication use. We genotyped 11 single nucleotide polymorphisms (SNPs) according to the HapMap Han Chinese Beijing databank across the AGTR1 gene to capture 96% of the haplotype variance in all SNPs with minor allele frequencies at least 5%. We also genotyped A1166C (rs5186) SNP with known associations with cardiovascular disease and analyzed associations of SNPs and haplotypes with DHF and linkage disequilibrium structure of the AGTR1 gene. In a single locus analysis, SNP rs16860760, rs389566, and rs5186 were associated with DHF (allele specific P = 0.004, 0.002, 0.002, respectively; permuted P = 0.045, 0.022, 0.027, respectively). SNP rs389566, with a minor allele frequency of 20.17%, had an odds ratio (OR) 2.03 for the autosomal dominant model [AA + AT: TT, 95% confidence interval (CI) 1.29-3.19; P = 0.0012] and 1.73 for the additive model (95% CI 1.21-2.48; P = 0.0018) corresponding to a population attributable risk fraction of 27.21%. The haplotypes in a linkage disequilibrium block of rs389566 (T-A-G and A-A-G) were also significantly associated with DHF (permuted P = 0.0125 and 0.0105, respectively). We identified risk-conferring genetic variants of the AGTR1 gene for DHF in a Chinese population.

Positionally cloned asthma susceptibility gene polymorphisms and disease risk in the British 1958 Birth Cohort

Objective:The aim of this study was to estimate the contribution of polymorphisms in the positionally cloned asthma candidate genes ADAM33, PHF11, DPP10, GPRA and PTGDR to the risk of asthma,...

Use of longitudinal data in genetic studies in the genome‐wide association studies era: summary of Group 14

Participants analyzed actual and simulated longitudinal data from the Framingham Heart Study for various metabolic and cardiovascular traits. The genetic information incorporated into these investigations ranged from selected single-nucleotide polymorphisms to genome-wide association arrays. Genotypes were incorporated using a broad range of methodological approaches including conditional logistic regression, linear mixed models, generalized estimating equations, linear growth curve estimation, growth modeling, growth mixture modeling, population attributable risk fraction based on survival functions under the proportional hazards models, and multivariate adaptive splines for the analysis of longitudinal data. The specific scientific questions addressed by these different approaches also varied, ranging from a more precise definition of the phenotype, bias reduction in control selection, estimation of effect sizes and genotype associated risk, to direct incorporation of genetic data into longitudinal modeling approaches and the exploration of population heterogeneity with regard to longitudinal trajectories. The group reached several overall conclusions: (1) The additional information provided by longitudinal data may be useful in genetic analyses. (2) The precision of the phenotype definition as well as control selection in nested designs may be improved, especially if traits demonstrate a trend over time or have strong age-of-onset effects. (3) Analyzing genetic data stratified for high-risk subgroups defined by a unique development over time could be useful for the detection of rare mutations in common multifactorial diseases. (4) Estimation of the population impact of genomic risk variants could be more precise. The challenges and computational complexity demanded by genome-wide single-nucleotide polymorphism data were also discussed.