Atlas of genetic and phenotypic associations across 42 female reproductive health diagnoses.

The genetic background of many female reproductive health diagnoses remains uncharacterized, compromising our understanding of the underlying biology. Here, we map the genetic architecture across 42 female-specific health conditions using data from up to 293,618 women from two large population-based cohorts, the Estonian Biobank and the FinnGen study. Our study illustrates the utility of genetic analyses in understanding women's health better.

Pathway level metabolomics analysis identifies carbon metabolism as a key factor of incident hypertension in the Estonian Biobank.

The purpose of this study was to find metabolic changes associated with incident hypertension in the volunteer-based Estonian Biobank. We used a subcohort of the Estonian Biobank where metabolite levels had been measured by mass-spectrometry (LC-MS, Metabolon platform). We divided annotated metabolites of 989 individuals into KEGG pathways, followed by principal component analysis of metabolites in each pathway, resulting in a dataset of 91 pathway components.

Characterizing the olfaction and dementia association in the community-based ARIC study.

Introduction: Few studies have characterized the association of olfaction with dementia in detail across diverse sociodemographic subgroups.

Methods: We examined the association of one-time-point olfactory status with incident dementia overall and by age, race, sex, and apolipoprotein E (APOE) ε4 status (n = 4470, mean age: 75 ± 5 years, 21% Black), and 5-year olfactory change with incident dementia (n = 2658) in the community-based Atherosclerosis Risk in Communities (ARIC) study.

Results: Compared to good olfaction, moderate olfaction (hazard ratio [HR]: 1.

The Dementia SomaSignal Test (dSST): A plasma proteomic predictor of 20-year dementia risk.

Introduction: There is an unmet need for tools to quantify dementia risk during its multi-decade preclinical/prodromal phase, given that current biomarkers predict risk over shorter follow-up periods and are specific to Alzheimer's disease.

Methods: Using high-throughput proteomic assays and machine learning techniques in the Atherosclerosis Risk in Communities study (n = 11,277), we developed the Dementia SomaSignal Test (dSST).

Results: In addition to outperforming existing plasma biomarkers, the dSST predicted mid-life dementia risk over a 20-year follow-up across two independent cohorts with different ethnic backgrounds (areas under the curve [AUCs]: dSST 0.

BinDel: Detecting Clinically Relevant Fetal Genomic Microdeletions Using Low-Coverage Whole-Genome Sequencing-Based NIPT.

Objective: Clinically pathogenic chromosomal microdeletions cause severe genetic disorders. Motivated by the absence of reliable screening of microdeletions during the first-trimester screening, we developed BinDel, a software tool to determine the risk of clinically relevant pathogenic fetal microdeletions from low-coverage whole-genome-sequencing (WGS) based NIPT data.

Methods: We developed novel computational software that employs a targeted approach with region-specific normalisation and calling procedures to detect microdeletion risk in predefined chromosomal regions.

Plasma proteomic characterization of motoric cognitive risk and mild cognitive impairment.

Introduction: Motoric cognitive risk (MCR) is a pre-dementia syndrome characterized by mobility and cognitive dysfunction. This study conducted a proteome-wide study of MCR and compared the proteomic signatures of MCR to that of mild cognitive impairment (MCI).

Methods: Participants were classified as MCR using a memory questionnaire and 4-meter walk.

Olfactory Function and Frailty in Older Adults.

This study investigated the relationship between olfactory impairment and frailty among 5,231 (mean age 75.3 (SD 5.0), 59% women, 22% Black) participants of the Atherosclerosis Risk in Communities (ARIC) Study cohort located in the U.

Poor Olfaction and Risk of Stroke in Older Adults: The Atherosclerosis Risk in Communities Study.

Background: Poor olfaction may be associated with adverse cerebrovascular events, but empirical evidence is limited. We aimed to investigate the association of olfaction with the risk of stroke in the Atherosclerosis Risk in Communities Study.

Methods: We included 5799 older adults with no history of stroke at baseline from 2011 to 2013 (75.

The effect of long-term adherence to physical activity recommendations in midlife on plasma proteins associated with frailty in the Atherosclerosis Risk in Communities (ARIC) study.

Clinical trials have shown favorable effects of exercise on frailty, supporting physical activity (PA) as a treatment and prevention strategy. Proteomics studies suggest that PA alters levels of many proteins, some of which may function as molecules in the biological processes underlying frailty. However, these studies have focused on structured exercise programs or cross-sectional PA-protein associations.

Genome-wide association study of anterior uveitis.

Background/aims: The purpose of this study is to define genetic factors associated with anterior uveitis through genome-wide association study (GWAS).

Methods: In this GWAS meta-analysis, we combined data from the FinnGen, Estonian Biobank and UK Biobank with a total of 12 205 anterior uveitis cases and 917 145 controls. We performed a phenome-wide association study (PheWAS) to investigate associations across phenotypes and traits.

Urinary Metal Levels, Cognitive Test Performance, and Dementia in the Multi-Ethnic Study of Atherosclerosis.

Importance: Metals are established neurotoxicants, but evidence of their association with cognitive performance at low chronic exposure levels is limited.

Objective: To investigate the association of urinary metal levels, individually and as a mixture, with cognitive tests and dementia diagnosis, including effect modification by apolipoprotein ε4 allele (APOE4).

Design, Setting, And Participants: The multicenter prospective cohort Multi-Ethnic Study of Atherosclerosis (MESA) was started from July 2000 to August 2002, with follow-up through 2018.

Leveraging large-scale multi-omics evidences to identify therapeutic targets from genome-wide association studies.

Background: Therapeutic targets supported by genetic evidence from genome-wide association studies (GWAS) show higher probability of success in clinical trials. GWAS is a powerful approach to identify links between genetic variants and phenotypic variation; however, identifying the genes driving associations identified in GWAS remains challenging. Integration of molecular quantitative trait loci (molQTL) such as expression QTL (eQTL) using mendelian randomization (MR) and colocalization analyses can help with the identification of causal genes.

Genome-wide meta-analysis conducted in three large biobanks expands the genetic landscape of lumbar disc herniations.

Given that lumbar disc herniation (LDH) is a prevalent spinal condition that causes significant individual suffering and societal costs, the genetic basis of LDH has received relatively little research. Our aim is to increase understanding of the genetic factors influencing LDH. We perform a genome-wide association analysis (GWAS) of LDH in the FinnGen project and in Estonian and UK biobanks, followed by a genome-wide meta-analysis to combine the results.

Establishment of trophoblast cell line derived from buffalo () parthenogenetic embryo.

We have established trophoblast cell lines, from parthenogenesis-derived buffalo blastocysts. The buffalo trophoblast cells were cultured continuously over 200 days and 21 passages. These cells were observed by phase-contrast microscopy for their morphology and characterized by reverse transcriptase polymerase chain reaction and immunofluorescence against trophoblast-specific markers and cytoskeletal proteins.

Proteomics identifies potential immunological drivers of postinfection brain atrophy and cognitive decline.

Infections have been associated with the incidence of Alzheimer disease and related dementias, but the mechanisms responsible for these associations remain unclear. Using a multicohort approach, we found that influenza, viral, respiratory, and skin and subcutaneous infections were associated with increased long-term dementia risk. These infections were also associated with region-specific brain volume loss, most commonly in the temporal lobe.

Genetic variants affect diurnal glucose levels throughout the day.

Circadian rhythms not only coordinate the timing of wake and sleep but also regulate homeostasis within the body, including glucose metabolism. However, the genetic variants that contribute to temporal control of glucose levels have not been previously examined. Using data from 420,000 individuals from the UK Biobank and replicating our findings in 100,000 individuals from the Estonian Biobank, we show that diurnal serum glucose is under genetic control.

Associations of psychosocial factors and cardiovascular health measured by Life's Essential 8: The Atherosclerosis Risk in Communities (ARIC) study.

Aims: Few studies investigate whether psychosocial factors (social isolation, social support, trait anger, and depressive symptoms) are associated with cardiovascular health, and none with the American Heart Association's new definition of cardiovascular health, Life's Essential 8 (LE8). Therefore, we assessed the cross-sectional associations of psychosocial factors with Life's Essential 8 and individual components of Life's Essential 8.

Methods: We included 11,311 Atherosclerosis Risk in Communities cohort participants (58% females; 23% Black; mean age 57 (standard deviation: 6) years) who attended Visit 2 (1990-1992) in this secondary data analysis using cross-sectional data from the ARIC cohort study.

Hearing Loss, Hearing Aids, and Functional Status.

Importance: Hearing loss may contribute to poor functional status via cognitive impairment and social isolation. Hearing aids may play a protective role by attenuating these downstream outcomes. However, population-based evidence is lacking.

Job-related exhaustion risk variant in UST is associated with dementia and DNA methylation.

Previous genome-wide association and replication study for job-related exhaustion indicated a risk variant, rs13219957 in the UST gene. Epidemiological studies suggest connection of stress-related conditions and dementia risk. Therefore, we first studied association of rs13219957 and register-based incident dementia using survival models in the Finnish National FINRISK study surveys (N = 26,693).