Genetic and Cellular Architecture of Breast Cancer Risk in Multi-Ancestry Studies of 159,297 Cases and 212,102 Controls.

Breast cancer genome-wide association studies (GWAS) have identified over 200 independent genome-wide significant susceptibility markers. However, most studies have focused on one or two ancestral groups. We examined breast cancer genetic architecture using GWAS summary statistics from African (AFR), East Asian (EAS), European (EUR) and Hispanic/Latina (H/L) samples, totaling 159,297 cases and 212,102 controls, comprising the largest multi-ancestry study of breast cancer to date.

Multi-Cohort High-Dimensional Proteomics Reveals Early Risk Markers for Lymphoid Cancer Subtypes.

This study aims to investigate the early stages of lymphoid malignancy pathogenesis and identify novel pre-diagnostic proteomic markers for lymphoma. Using the SomaScan-7K platform, we analyzed 6,412 unique plasma proteins in a case-cohort study nested within the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort, comprising 4,565 participants (484 incident lymphoid malignancy cases, median follow-up 9 years). We identified over 500 unique protein-lymphoid malignancy associations.

Exposure and toxicokinetics of microplastics in arthropods: Mechanisms and consequences.

Arthropoda, the largest and the most diverse invertebrate Phylum, are increasingly impacted by microplastic (MP) pollution across varied range of habitats. This review synthesizes toxicity of MPs in different taxa of arthropods with references to exposure route, tissue level accumulation and toxicokinetic behaviour with a focus on physiological outcomes. This review article comprehensively identified that gut and gill are the primary sites of MP accumulation.

Projecting individualized probabilities of lifetime all-cancer risk.

Introduction: Technological advances and direct-to-consumer marketing have unearthed significant organic demand from patients for cancer screening and prevention. However, in the absence of strong data or guidelines, physicians have minimal support on how to approach patients in clinical practice.

Methods: We projected individualized probabilities of 10-year and lifetime cancer risk across a population as well as potential improvement with healthy behaviors in the UK Biobank.

Microplastic toxicity in aquatic organisms across phylogeny.

Microplastic (MP) contamination of aquatic ecosystem had been escalated several folds and became concerning for the inhabiting organisms. Their accumulation in aquatic biota, ranging from lower invertebrates to higher vertebrates, underscores the severity of their toxicological impact and raises critical concerns for ecosystem health. Many of the researchers concentrated on assessment of MP distribution across environmental compartments and analysis of the physicochemical characteristics and their bioaccumulation in freshwater and marine species.

Perceived and observed biases within scientific communities: a case study in movement ecology.

Who conducts biological research, where they do it and how results are disseminated vary among geographies and identities. Identifying and documenting these forms of bias by research communities is a critical step towards addressing them. We documented perceived and observed biases in movement ecology, a rapidly expanding sub-discipline of biology, which is strongly underpinned by fieldwork and technology use.

Germline genetic variation impacts clonal hematopoiesis landscape and progression to malignancy.

With age, clonal expansions occur pervasively across normal tissues yet only in rare instances lead to cancer, despite being driven by well-established cancer drivers. Characterization of the factors that influence clonal progression is needed to inform interventional approaches. Germline genetic variation influences cancer risk and shapes tumor mutational profile, but its influence on the mutational landscape of normal tissues is not well known.

Discovering plasma proteins associated with breast cancer incidence in post-menopausal women in ARIC.

Background: Plasma proteomic data can be used to discover breast cancer risk biomarkers beyond established risk factors. Discovery using a large-scale platform in a diverse population is needed.

Methods: We investigated 4,712 plasma proteins and breast cancer risk among post-menopausal women in a prospective cohort analysis in the Atherosclerosis Risk in Communities study.

Methodological opportunities in genomic data analysis to advance health equity.

The causes and consequences of inequities in genomic research and medicine are complex and widespread. However, it is widely acknowledged that underrepresentation of diverse populations in human genetics research risks exacerbating existing health disparities. Efforts to improve diversity are ongoing, but an often-overlooked source of inequity is the choice of analytical methods used to process, analyse and interpret genomic data.

A Genome-wide Association study of Buccal Mucosa Cancer in India and Multi-ancestry Meta-analysis Identifies Novel Risk Loci and Gene-environment Interactions.

Genome-wide association studies (GWAS) of oral cancers (OC) to date have focused predominantly on European Ancestry (EA) populations. India faces an excess burden of OC, but the most common site of occurrence is the cancer of the buccal mucosa, which is relatively rare in EA populations. We conducted a GWAS of buccal mucosa cancer (BMC) comprising 2,160 BMC cases and 2,325 controls from different geographical locations in India.

Expanding scope of genetic studies in the era of biobanks.

Biobanks have become pivotal in genetic research, particularly through genome-wide association studies (GWAS), driving transformative insights into the genetic basis of complex diseases and traits through the integration of genetic data with phenotypic, environmental, family history, and behavioral information. This review explores the distinct design and utility of different biobanks, highlighting their unique contributions to genetic research. We further discuss the utility and methodological advances in combining data from disease-specific study or consortia with that of biobanks, especially focusing on summary statistics based meta-analysis.

Genetic and Nongenetic Risk Factors for Breast Cancer Risk Estimation.

Importance: Most breast cancers in Africa are diagnosed at advanced stages. Improved risk prediction tools to optimize screening and earlier diagnosis are urgently needed.

Objective: To build a comprehensive breast cancer risk estimation model by integrating a polygenic risk score (PRS), pathogenic variants (PVs) in high- or moderate-penetrance genes, and a questionnaire-based risk calculator.

Correlations Within and Between Highly Multiplexed Proteomic Assays of Human Plasma.

Introduction: The number of assays on proteomic platforms has grown rapidly. The leading platforms, SomaScan and Olink, have strengths and limitations. Comparisons of precision on the latest platforms-SomaScan 11k and Olink Explore HT-have not yet been established.

Leveraging genetic ancestry continuum information to interpolate PRS for admixed populations.

The relatively low representation of admixed populations in both discovery and fine-tuning individual-level datasets limits polygenic risk score (PRS) development and equitable clinical translation for admixed populations. Under the assumption that the most informative PRS weight for a homogeneous sample varies linearly in an ancestry continuum space, we introduce a Genetic tance-assisted PRS mbination Pipeline for erse Genetic ncestrie () to interpolate a harmonized PRS for diverse, especially admixed, ancestries, leveraging multiple PRS weights fine-tuned within single-ancestry samples and genetic distance. DiscoDivas treats ancestry as a continuous variable and does not require shifting between different models when calculating PRS for different ancestries.

Alcohol Consumption Does not Modify the Polygenic Risk Score-Based Genetic Risk of Breast Cancer in Postmenopausal Women: Atherosclerosis Risk in Communities Study.

High genetic risk and alcohol consumption ≥1 drink/day are associated with increased breast cancer risk. However, the interaction between alcohol and genetics on breast cancer risk is poorly understood, including in populations not enriched with daily drinkers. We prospectively studied 5,651 White and Black postmenopausal women in the Atherosclerosis Risk in Communities study.

Ancestrally diverse genome-wide association analysis highlights ancestry-specific differences in genetic regulation of plasma protein levels.

Fully characterizing the genetic architecture of circulating proteins in multi-ancestry populations provides an unprecedented opportunity to gain insights into the etiology of complex diseases. We characterized and contrasted the genetic associations of plasma proteomes in 9,455 participants of European and African (19.8%) ancestry from the Atherosclerosis Risk in Communities Study.

Validation of candidate protein biomarkers previously identified by genetic instruments for prostate cancer risk: A prospective cohort analysis of directly measured protein levels in the ARIC study.

Background: Multiple novel protein biomarkers have been shown to be associated with prostate cancer risk using genetic instruments. This study aimed to externally validate the associations of 30 genetically predicted candidate proteins with prostate cancer risk using aptamer-based levels in US Black and White men in the Atherosclerosis Risk in Communities (ARIC) study. Plasma protein levels were previously measured by SomaScan® using the blood collected in 1990-1992.

Genome-wide large-scale multi-trait analysis characterizes global patterns of pleiotropy and unique trait-specific variants.

Genome-wide association studies (GWAS) have found widespread evidence of pleiotropy, but characterization of global patterns of pleiotropy remain highly incomplete due to insufficient power of current approaches. We develop fastASSET, a method that allows efficient detection of variant-level pleiotropic association across many traits. We analyze GWAS summary statistics of 116 complex traits of diverse types collected from the GRASP repository and large GWAS Consortia.

Plasma proteomic comparisons change as coverage expands for SomaLogic and Olink.

The number of assays on highly-multiplexed proteomic platforms has grown tenfold over the past 15 years from less than 1,000 to >11,000. The leading aptamer-based and antibody-based platforms have different strengths. For example, Eldjarn et al demonstrated that the aptamer-based SomaScan 5k (4,907 assays, assessed in the Icelandic 36K) and the antibody-based Olink Explore 3072 (2,931 assays, assessed in the UK BioBank) had a similar number of -pQTLs among all targets (2,120 vs.

Characterization and ecological risk assessment of microplastics accumulated in sea water, sand, sediment, shell water and selected tissues of hermit crab of Sundarban Biosphere Reserve.

Sundarban, a Ramsar site of India, has been encountering an ecological threat due to the presence of microplastic (MP) wastes generated from different anthropogenic sources. Clibanarius longitarsus, an intertidal hermit crab of Sundarban Biosphere Reserve, resides within the abandoned shell of a gastropod mollusc, Telescopium telescopium. We characterized and estimated the MP in the gills and gut of hermit crab, as well as in the water present in its occupied gastropod shell.

Wasm-iCARE: a portable and privacy-preserving web module to build, validate, and apply absolute risk models.

Objectives: Absolute risk models estimate an individual's future disease risk over a specified time interval. Applications utilizing server-side risk tooling, the R-based iCARE (R-iCARE), to build, validate, and apply absolute risk models, face limitations in portability and privacy due to their need for circulating user data in remote servers for operation. We overcome this by porting iCARE to the web platform.