Minority-centric meta-analyses of blood lipid levels identify novel loci in the Population Architecture using Genomics and Epidemiology (PAGE) study.

Lipid levels are important markers for the development of cardio-metabolic diseases. Although hundreds of associated loci have been identified through genetic association studies, the contribution of genetic factors to variation in lipids is not fully understood, particularly in U.S.

Effects of Colorectal Cancer Risk Factors on the Association Between Aspirin and Colorectal Cancer.

Background/aim: We investigated the effect of aspirin on colorectal cancer (CRC) risk among subgroups of women with and without risk factors for CRC.

Patients And Methods: Using data from the Women's Health Initiative, we estimated hazard ratios for CRC in association with aspirin use, with stratifications by cardiovascular disease (CVD) risk status, family history of CRC, and history of colorectal polypectomy.

Results: Aspirin was associated with a lower risk of CRC among women with low/normal or high CVD-risk status; no family history of CRC; or a history of colonoscopy with polypectomy.

Genetic analyses of diverse populations improves discovery for complex traits.

Genome-wide association studies (GWAS) have laid the foundation for investigations into the biology of complex traits, drug development and clinical guidelines. However, the majority of discovery efforts are based on data from populations of European ancestry. In light of the differential genetic architecture that is known to exist between populations, bias in representation can exacerbate existing disease and healthcare disparities.

Genetic Predisposition Impacts Clinical Changes in a Lifestyle Coaching Program.

Both genetic and lifestyle factors contribute to an individual's disease risk, suggesting a multi-omic approach is essential for personalized prevention. Studies have examined the effectiveness of lifestyle coaching on clinical outcomes, however, little is known about the impact of genetic predisposition on the response to lifestyle coaching. Here we report on the results of a real-world observational study in 2531 participants enrolled in a commercial "Scientific Wellness" program, which combines multi-omic data with personalized, telephonic lifestyle coaching.

A Multi-omic Association Study of Trimethylamine N-Oxide.

Trimethylamine N-oxide (TMAO) is a circulating metabolite that has been implicated in the development of atherosclerosis and cardiovascular disease (CVD). In this paper, we identify blood markers, metabolites, proteins, gut microbiota patterns, and diets that are significantly associated with levels of plasma TMAO. We find that kidney markers are strongly associated with TMAO and identify CVD-related proteins that are positively correlated with TMAO.

Influence of Smoking, Body Mass Index, and Other Factors on the Preventive Effect of Nonsteroidal Anti-Inflammatory Drugs on Colorectal Cancer Risk.

Nonsteroidal anti-inflammatory drugs' (NSAID) use has consistently been associated with lower risk of colorectal cancer; however, studies showed inconsistent results on which cohort of individuals may benefit most. We performed multivariable logistic regression analysis to systematically test for the interaction between regular use of NSAIDs and other lifestyle and dietary factors on colorectal cancer risk among 11,894 cases and 15,999 controls. Fixed-effects meta-analyses were used for stratified analyses across studies for each risk factor and to summarize the estimates from interactions.

Novel Common Genetic Susceptibility Loci for Colorectal Cancer.

Background: Previous genome-wide association studies (GWAS) have identified 42 loci (P < 5 × 10-8) associated with risk of colorectal cancer (CRC). Expanded consortium efforts facilitating the discovery of additional susceptibility loci may capture unexplained familial risk.

Methods: We conducted a GWAS in European descent CRC cases and control subjects using a discovery-replication design, followed by examination of novel findings in a multiethnic sample (cumulative n = 163 315).

Determining Risk of Colorectal Cancer and Starting Age of Screening Based on Lifestyle, Environmental, and Genetic Factors.

Background & Aims: Guidelines for initiating colorectal cancer (CRC) screening are based on family history but do not consider lifestyle, environmental, or genetic risk factors. We developed models to determine risk of CRC, based on lifestyle and environmental factors and genetic variants, and to identify an optimal age to begin screening.

Methods: We collected data from 9748 CRC cases and 10,590 controls in the Genetics and Epidemiology of Colorectal Cancer Consortium and the Colorectal Transdisciplinary study, from 1992 through 2005.

Correction: Genome-wide physical activity interactions in adiposity - A meta-analysis of 200,452 adults.

[This corrects the article DOI: 10.1371/journal.pgen.

Fine-mapping of lipid regions in global populations discovers ethnic-specific signals and refines previously identified lipid loci.

Genome-wide association studies have identified over 150 loci associated with lipid traits, however, no large-scale studies exist for Hispanics and other minority populations. Additionally, the genetic architecture of lipid-influencing loci remains largely unknown. We performed one of the most racially/ethnically diverse fine-mapping genetic studies of HDL-C, LDL-C, and triglycerides to-date using SNPs on the MetaboChip array on 54,119 individuals: 21,304 African Americans, 19,829 Hispanic Americans, 12,456 Asians, and 530 American Indians.

Strategies for Enriching Variant Coverage in Candidate Disease Loci on a Multiethnic Genotyping Array.

Investigating genetic architecture of complex traits in ancestrally diverse populations is imperative to understand the etiology of disease. However, the current paucity of genetic research in people of African and Latin American ancestry, Hispanic and indigenous peoples in the United States is likely to exacerbate existing health disparities for many common diseases. The Population Architecture using Genomics and Epidemiology, Phase II (PAGE II), Study was initiated in 2013 by the National Human Genome Research Institute to expand our understanding of complex trait loci in ethnically diverse and well characterized study populations.

Variant Discovery and Fine Mapping of Genetic Loci Associated with Blood Pressure Traits in Hispanics and African Americans.

Despite the substantial burden of hypertension in US minority populations, few genetic studies of blood pressure have been conducted in Hispanics and African Americans, and it is unclear whether many of the established loci identified in European-descent populations contribute to blood pressure variation in non-European descent populations. Using the Metabochip array, we sought to characterize the genetic architecture of previously identified blood pressure loci, and identify novel cardiometabolic variants related to systolic and diastolic blood pressure in a multi-ethnic US population including Hispanics (n = 19,706) and African Americans (n = 18,744). Several known blood pressure loci replicated in African Americans and Hispanics.

Genetic architecture of colorectal cancer.

Colorectal cancer (CRC) is a complex disease that develops as a consequence of both genetic and environmental risk factors. A small proportion (3-5%) of cases arise from hereditary syndromes predisposing to early onset CRC as a result of mutations in over a dozen well defined genes. In contrast, CRC is predominantly a late onset 'sporadic' disease, developing in individuals with no obvious hereditary syndrome.

Genetic variation predicts serum lycopene concentrations in a multiethnic population of postmenopausal women.

Background: The consumption and blood concentrations of lycopene are both positively and inversely associated with the risk of several chronic diseases. The inconsistences in lycopene disease association studies may stem from a lack of knowledge about the genetic variation in the synthesis, metabolism, and deposition of transport and binding proteins, which potentially influence serum lycopene concentrations.

Objective: We examined the association between variation across the genome and serum concentrations of lycopene in a multiethnic population.

Clustering and determinants of cardiometabolic risk factors among Filipino young adults.

Background: With modernization, cardiometabolic disease risk has increased in low and middle-income countries. To better understand cardiometabolic disease etiology, we evaluated the patterning risk factors in a susceptible young adult population.

Methods And Results: Participants included 1,621 individuals from the 2005 Cebu Longitudinal Health and Nutrition Survey.

Cluster analysis reveals important determinants of cardiometabolic risk patterns in Filipino women.

With modernization, the Philippines has experienced increasing rates of obesity and related cardiometabolic diseases. Studying how risk factors cluster in individuals may offer insight into cardiometabolic disease etiology. We used cluster analysis to group women who share the following cardiometabolic biomarkers: fasting triglycerides, HDL-C and LDL-C, C-reactive protein, systolic and diastolic blood pressure, homeostasis model assessment of insulin resistance, and fasting glucose.