Dataset Information

Comparison of family history and SNPs for predicting risk of complex disease.

ABSTRACT: The clinical utility of family history and genetic tests is generally well understood for simple Mendelian disorders and rare subforms of complex diseases that are directly attributable to highly penetrant genetic variants. However, little is presently known regarding the performance of these methods in situations where disease susceptibility depends on the cumulative contribution of multiple genetic factors of moderate or low penetrance. Using quantitative genetic theory, we develop a model for studying the predictive ability of family history and single nucleotide polymorphism (SNP)-based methods for assessing risk of polygenic disorders. We show that family history is most useful for highly common, heritable conditions (e.g., coronary artery disease), where it explains roughly 20%-30% of disease heritability, on par with the most successful SNP models based on associations discovered to date. In contrast, we find that for diseases of moderate or low frequency (e.g., Crohn disease) family history accounts for less than 4% of disease heritability, substantially lagging behind SNPs in almost all cases. These results indicate that, for a broad range of diseases, already identified SNP associations may be better predictors of risk than their family history-based counterparts, despite the large fraction of missing heritability that remains to be explained. Our model illustrates the difficulty of using either family history or SNPs for standalone disease prediction. On the other hand, we show that, unlike family history, SNP-based tests can reveal extreme likelihood ratios for a relatively large percentage of individuals, thus providing potentially valuable adjunctive evidence in a differential diagnosis.

SUBMITTER: Do CB

PROVIDER: S-EPMC3469463 | biostudies-literature | 2012

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Comparison of family history and SNPs for predicting risk of complex disease.

Do Chuong B CB Hinds David A DA Francke Uta U Eriksson Nicholas N

PLoS genetics 20121011 10

The clinical utility of family history and genetic tests is generally well understood for simple Mendelian disorders and rare subforms of complex diseases that are directly attributable to highly penetrant genetic variants. However, little is presently known regarding the performance of these methods in situations where disease susceptibility depends on the cumulative contribution of multiple genetic factors of moderate or low penetrance. Using quantitative genetic theory, we develop a model for ...[more]

PMID: 23071447

Similar Datasets

Project description:IntroductionThe generational relevance for determining disease risk for the leading causes of morbidity and mortality for U.S. adults is a source of debate.MethodsData on 12,300 adults (Add Health Study Members) participating in Wave V (2016-2018) of the National Longitudinal Study of Adolescent to Adult Health (also known as Add Health) were merged with data from respondents' parents (n=2,013) participating in the Add Health Parent Study (2015-2017). Analyses beginning in January 2020 examined the concordance in lifetime occurrence of chronic conditions across 4 generations, including cardiovascular disease, diabetes, hypertension, hyperlipidemia, obesity, cancer, and depression and examined the associations between individual disease history and ones' family health history for the same condition.ResultsMean ages were 37.4 years for Add Health Study Members and 62.9 years for Add Health Parent Study mothers. The histories of mothers from the Add Health Parent Study on hyperlipidemia (AOR=1.61, 95% CI=1.04, 2.48), obesity (AOR=1.77, 95% CI=1.27, 2.48), and depression (AOR=1.87, 95% CI=1.19, 2.95) were significantly associated with increased odds of Add Health Study Member report of these conditions. Maternal great grandparent hyperlipidemia history was significantly associated with the Add Health Study Member hyperlipidemia (AOR=2.81, 95% CI=1.51, 5.21). Histories of diabetes in maternal grandfather (AOR=2.41, 95% CI=1.24, 4.69) and maternal great grandparent (AOR=3.05, 95% CI=1.45, 6.43) were significantly associated with Add Health Study Member diabetes. Each additional point in the Add Health Parent Study mothers' cardiometabolic risk factor index was associated with an 11% increase (incidence rate ratio=1.11, 95% CI=1.04, 1.19) in the expected count of cardiometabolic risk conditions for the Add Health Study Members.ConclusionsMultigenerational health histories have value for quantifying the probability of diabetes, obesity, depression, and hyperlipidemia in early mid-adulthood. Family health history knowledge is relevant for health promotion and disease prevention strategies.

Project description:Periodontal disease (PD) shares common risk factors with cardiovascular disease. Our hypothesis was that having a family history of myocardial infarction (FamHxMI) may be a novel risk factor for PD. Risk assessment based on FamHxMI, conditional on smoking status, was examined given the strong influence of smoking on PD. Exploratory analysis with inflammatory biomarkers and genetic determinants was conducted to understand potential mechanistic links. The Women's Genome Health Study (WGHS) is a prospective cohort of US female health care professionals who provided blood samples at baseline in the Women's Health Study, a 2 × 2 factorial clinical trial investigating vitamin E and aspirin in the prevention of cardiovascular disease and cancer. PD was ascertained via self-report over 12 y of follow-up. Prevalence (3,442 cases), incidence (1,365 cases), and survival analysis of PD were investigated for associations of FamHxMI as well as in strata of FamHxMI by smoking. Kruskal-Wallis, chi-square tests, multivariate regression, and Cox proportional hazard models were used for the analyses. In the WGHS, women with FamHxMI showed higher risk of ever having PD. A particularly high-risk group of having both FamHxMI and smoking at baseline was highlighted in the prevalence and risk of developing PD. PD risk increased according to the following strata: no FamHxMI and nonsmokers (reference), FamHxMI and nonsmokers (hazard ratio [HR] = 1.2, 95% CI = 1.0 to 1.5), smokers without FamHxMI (HR = 1.3, 95% CI = 1.2 to 1.5), and smokers with FamHxMI (HR = 1.5, 95% CI = 1.2 to 1.8). An independent analysis by the dental Atherosclerosis Risk in Communities study ( N = 5,552) identified more severe periodontitis cases among participants in the high-risk group (smokers with FamHxMI). Further examination of interactions among inflammatory biomarkers or genetic exploration with FamHxMI did not explain the risk increase of PD associated with FamHxMI in the WGHS. Future efforts based on an integrative-omics approach may facilitate validation of these findings and suggest a mechanistic link between PD and FamHxMI.

Dataset Information

Comparison of family history and SNPs for predicting risk of complex disease.

Publications

Comparison of family history and SNPs for predicting risk of complex disease.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets