Evidence of Novel Susceptibility Variants for Prostate Cancer and a Multiancestry Polygenic Risk Score Associated with Aggressive Disease in Men of African Ancestry.

Background: Genetic factors play an important role in prostate cancer (PCa) susceptibility.

Objective: To discover common genetic variants contributing to the risk of PCa in men of African ancestry.

Design, Setting, And Participants: We conducted a meta-analysis of ten genome-wide association studies consisting of 19378 cases and 61620 controls of African ancestry.

A Rare Germline HOXB13 Variant Contributes to Risk of Prostate Cancer in Men of African Ancestry.

A rare African ancestry-specific germline deletion variant in HOXB13 (X285K, rs77179853) was recently reported in Martinican men with early-onset prostate cancer. Given the role of HOXB13 germline variation in prostate cancer, we investigated the association between HOXB13 X285K and prostate cancer risk in a large sample of 22 361 African ancestry men, including 11 688 prostate cancer cases. The risk allele was present only in men of West African ancestry, with an allele frequency in men that ranged from 0.

Discovery and fine-mapping of height loci via high-density imputation of GWASs in individuals of African ancestry.

Although many loci have been associated with height in European ancestry populations, very few have been identified in African ancestry individuals. Furthermore, many of the known loci have yet to be generalized to and fine-mapped within a large-scale African ancestry sample. We performed sex-combined and sex-stratified meta-analyses in up to 52,764 individuals with height and genome-wide genotyping data from the African Ancestry Anthropometry Genetics Consortium (AAAGC).

Trans-ancestry genome-wide association meta-analysis of prostate cancer identifies new susceptibility loci and informs genetic risk prediction.

Prostate cancer is a highly heritable disease with large disparities in incidence rates across ancestry populations. We conducted a multiancestry meta-analysis of prostate cancer genome-wide association studies (107,247 cases and 127,006 controls) and identified 86 new genetic risk variants independently associated with prostate cancer risk, bringing the total to 269 known risk variants. The top genetic risk score (GRS) decile was associated with odds ratios that ranged from 5.

Author Correction: Germline variation at 8q24 and prostate cancer risk in men of European ancestry.

The original version of this Article contained an error in the spelling of the author Manuela Gago-Dominguez, which was incorrectly given as Manuela G. Dominguez. This has now been corrected in both the PDF and HTML versions of the Article.

Germline variation at 8q24 and prostate cancer risk in men of European ancestry.

Chromosome 8q24 is a susceptibility locus for multiple cancers, including prostate cancer. Here we combine genetic data across the 8q24 susceptibility region from 71,535 prostate cancer cases and 52,935 controls of European ancestry to define the overall contribution of germline variation at 8q24 to prostate cancer risk. We identify 12 independent risk signals for prostate cancer (p < 4.

A Mixed-Methods Study to Examine the Role of Psychosocial Stress and Air Pollution on Hypertension in Mexican-Origin Hispanics.

Purpose: Independent and combined effects of air pollution and psychosocial stressors on hypertension, a risk factor for cardiovascular disease, among Hispanics are not well studied.

Methods: We administered a pilot-tested questionnaire on individual- and neighborhood-level psychosocial stressors, developed with community input, to nearly 2500 individuals from the MD Anderson Cancer Center cohort of Mexican-Americans. We used data from local air quality monitors to estimate individual exposures to ozone (O) and fine particulate matter (PM) for the 12-month period preceding enrollment using inverse distance interpolation.

Two Novel Susceptibility Loci for Prostate Cancer in Men of African Ancestry.

Prostate cancer incidence is 1.6-fold higher in African Americans than in other populations. The risk factors that drive this disparity are unknown and potentially consist of social, environmental, and genetic influences.

Discovery and fine-mapping of adiposity loci using high density imputation of genome-wide association studies in individuals of African ancestry: African Ancestry Anthropometry Genetics Consortium.

Genome-wide association studies (GWAS) have identified >300 loci associated with measures of adiposity including body mass index (BMI) and waist-to-hip ratio (adjusted for BMI, WHRadjBMI), but few have been identified through screening of the African ancestry genomes. We performed large scale meta-analyses and replications in up to 52,895 individuals for BMI and up to 23,095 individuals for WHRadjBMI from the African Ancestry Anthropometry Genetics Consortium (AAAGC) using 1000 Genomes phase 1 imputed GWAS to improve coverage of both common and low frequency variants in the low linkage disequilibrium African ancestry genomes. In the sex-combined analyses, we identified one novel locus (TCF7L2/HABP2) for WHRadjBMI and eight previously established loci at P < 5×10-8: seven for BMI, and one for WHRadjBMI in African ancestry individuals.

A Meta-analysis of Multiple Myeloma Risk Regions in African and European Ancestry Populations Identifies Putatively Functional Loci.

Background: Genome-wide association studies (GWAS) in European populations have identified genetic risk variants associated with multiple myeloma.

Methods: We performed association testing of common variation in eight regions in 1,318 patients with multiple myeloma and 1,480 controls of European ancestry and 1,305 patients with multiple myeloma and 7,078 controls of African ancestry and conducted a meta-analysis to localize the signals, with epigenetic annotation used to predict functionality.

Results: We found that variants in 7p15.

Atlas of prostate cancer heritability in European and African-American men pinpoints tissue-specific regulation.

Although genome-wide association studies have identified over 100 risk loci that explain ∼33% of familial risk for prostate cancer (PrCa), their functional effects on risk remain largely unknown. Here we use genotype data from 59,089 men of European and African American ancestries combined with cell-type-specific epigenetic data to build a genomic atlas of single-nucleotide polymorphism (SNP) heritability in PrCa. We find significant differences in heritability between variants in prostate-relevant epigenetic marks defined in normal versus tumour tissue as well as between tissue and cell lines.

Meta-analysis of genome-wide association studies discovers multiple loci for chronic lymphocytic leukemia.

Chronic lymphocytic leukemia (CLL) is a common lymphoid malignancy with strong heritability. To further understand the genetic susceptibility for CLL and identify common loci associated with risk, we conducted a meta-analysis of four genome-wide association studies (GWAS) composed of 3,100 cases and 7,667 controls with follow-up replication in 1,958 cases and 5,530 controls. Here we report three new loci at 3p24.

The Association of Smoking with English and Spanish Language Use as a Proxy of Acculturation Among Mexican-Americans.

To better characterize the relation of acculturation, based on language use, to smoking status among Mexican-Americans, a large study sample from an ongoing cohort of Mexican-American households in Texas was stratified into current smokers and non-smokers. Four language-use groups were created based on Low/High use of Spanish and English, representing different degrees of acculturation. Participants who reported high English but low Spanish use had the highest smoking prevalence (20.

Prostate Cancer Susceptibility in Men of African Ancestry at 8q24.

The 8q24 region harbors multiple risk variants for distinct cancers, including >8 for prostate cancer. In this study, we conducted fine mapping of the 8q24 risk region (127.8-128.

Relative survival in patients with chronic-phase chronic myeloid leukaemia in the tyrosine-kinase inhibitor era: analysis of patient data from six prospective clinical trials.

Background: Tyrosine-kinase inhibitors improve overall survival in patients with chronic myeloid leukaemia in chronic phase (CML-CP). Survival compared with the general population by age, response, and type of tyrosine-kinase inhibitor is not known. With use of data from trials of tyrosine kinase inhibitors, we compared overall survival in patients with newly diagnosed CML-CP to that of general population.

Using a Community-Engaged Approach to Develop a Bilingual Survey about Psychosocial Stressors among Individuals of Mexican Origin.

Hypertension is on the rise among Hispanics and is highest among those of Mexican origin. Recent studies have found a positive association between air pollution and blood pressure and hypertension. Moreover, a link between hypertension and adverse socioeconomic conditions is well established.

The Relationship between Native American Ancestry, Body Mass Index and Diabetes Risk among Mexican-Americans.

Higher body mass index (BMI) is a well-established risk factor for type 2 diabetes, and rates of obesity and type 2 diabetes are substantially higher among Mexican-Americans relative to non-Hispanic European Americans. Mexican-Americans are genetically diverse, with a highly variable distribution of Native American, European, and African ancestries. Here, we evaluate the role of Native American ancestry on BMI and diabetes risk in a well-defined Mexican-American population.

Integration of multiethnic fine-mapping and genomic annotation to prioritize candidate functional SNPs at prostate cancer susceptibility regions.

Interpretation of biological mechanisms underlying genetic risk associations for prostate cancer is complicated by the relatively large number of risk variants (n = 100) and the thousands of surrogate SNPs in linkage disequilibrium. Here, we combined three distinct approaches: multiethnic fine-mapping, putative functional annotation (based upon epigenetic data and genome-encoded features), and expression quantitative trait loci (eQTL) analyses, in an attempt to reduce this complexity. We examined 67 risk regions using genotyping and imputation-based fine-mapping in populations of European (cases/controls: 8600/6946), African (cases/controls: 5327/5136), Japanese (cases/controls: 2563/4391) and Latino (cases/controls: 1034/1046) ancestry.

Methodological Considerations in Estimation of Phenotype Heritability Using Genome-Wide SNP Data, Illustrated by an Analysis of the Heritability of Height in a Large Sample of African Ancestry Adults.

Height has an extremely polygenic pattern of inheritance. Genome-wide association studies (GWAS) have revealed hundreds of common variants that are associated with human height at genome-wide levels of significance. However, only a small fraction of phenotypic variation can be explained by the aggregate of these common variants.

A cross-sectional analysis of polycyclic aromatic hydrocarbons and diesel particulate matter exposures and hypertension among individuals of Mexican origin.

Background: Epidemiological studies have found that particulate matter is associated with increases in blood pressure. Yet, less is known about the effects of specific sources or constituents of particulate matter, such as diesel particulate matter or polycyclic aromatic hydrocarbons (PAHs). We evaluated associations between self-reported hypertension and residential air levels of diesel particulate matter and PAHs among individuals of Mexican origin living in a large inner city.

Family Cohesion and Moderate-to-Vigorous Physical Activity Among Mexican Origin Adolescents: A Longitudinal Perspective.

Background: Existing racial/ethnic disparities in physical activity during childhood increase Hispanics' risk of developing chronic diseases, which serves to increase health disparities. This study examined associations of family cohesion and conflict with self-reported moderate-to-vigorous physical activity (MVPA), controlling for psychosocial covariates such as subjective social status, anxiety, and sensation-seeking.

Methods: 1000 Mexican origin adolescents reported their MVPA levels approximately 2 years apart.

Assessing the Optimum Use of Androgen-Deprivation Therapy in High-Risk Prostate Cancer Patients Undergoing External Beam Radiation Therapy.

The optimum use of androgen deprivation therapy (ADT) in high-risk prostate cancer patients has not been defined in the setting of dose-escalated external beam radiation therapy. A retrospective analysis of 1,290 patients with high-risk prostate cancer from June 1987 through March 2010 treated with external beam radiation therapy was performed. Median follow-up was 7.