Haplotype analysis identifies functional elements in monoclonal gammopathy of unknown significance.

Genome-wide association studies (GWASs) based on common single nucleotide polymorphisms (SNPs) have identified several loci associated with the risk of monoclonal gammopathy of unknown significance (MGUS), a precursor condition for multiple myeloma (MM). We hypothesized that analyzing haplotypes might be more useful than analyzing individual SNPs, as it could identify functional chromosomal units that collectively contribute to MGUS risk. To test this hypothesis, we used data from our previous GWAS on 992 MGUS cases and 2910 controls from three European populations.

An atlas of genetic determinants of forearm fracture.

Osteoporotic fracture is among the most common and costly of diseases. While reasonably heritable, its genetic determinants have remained elusive. Forearm fractures are the most common clinically recognized osteoporotic fractures with a relatively high heritability.

Genomic atlas of the plasma metabolome prioritizes metabolites implicated in human diseases.

Metabolic processes can influence disease risk and provide therapeutic targets. By conducting genome-wide association studies of 1,091 blood metabolites and 309 metabolite ratios, we identified associations with 690 metabolites at 248 loci and associations with 143 metabolite ratios at 69 loci. Integrating metabolite-gene and gene expression information identified 94 effector genes for 109 metabolites and 48 metabolite ratios.

Assessment of the genetic and clinical determinants of hip fracture risk: Genome-wide association and Mendelian randomization study.

Hip fracture is the clinically most important fracture, but the genetic architecture of hip fracture is unclear. Here, we perform a large-scale hip fracture genome-wide association study meta-analysis and Mendelian randomization study using five cohorts from European biobanks. The results show that five genetic signals associate with hip fractures.

The influence of adult hip shape genetic variants on adolescent hip shape: Findings from a population-based DXA study.

Objective: Hip shape is a well-recognized risk factor for hip osteoarthritis (OA) and hip fracture. We aimed to investigate whether the genetic variants known to be associated with adult hip shape were also associated with adolescent hip shape.

Methods: Hip DXA scans, obtained in offspring from the Avon Longitudinal Study of Parents and Children (ALSPAC) at two time points (mean ages 13.

BMD-Related Genetic Risk Scores Predict Site-Specific Fractures as Well as Trabecular and Cortical Bone Microstructure.

Context: It is important to identify patients at highest risk of fractures.

Objective: To compare the separate and combined performances of bone-related genetic risk scores (GRSs) for prediction of forearm, hip and vertebral fractures separately, as well as of trabecular and cortical bone microstructure parameters separately.

Design, Setting, And Participants: Using 1103 single nucleotide polymorphisms (SNPs) independently associated with estimated bone mineral density of the heel (eBMD), we developed a weighted GRS for eBMD and determined its contribution to fracture prediction beyond 2 previously developed GRSs for femur neck BMD (49 SNPs) and lumbar spine BMD (48 SNPs).

[Preparing for the licence to prescribe in medical school - a questionnaire study on medical students professional confidence in the art of prescribing].

A prerequisite for rational use of medicines is adequate prescribing skills; drug treatment is a complex task requiring diagnostic competence combined with pharmacologic knowledge and patient communication skills. Acquiring professional confidence in the art of prescribing is essential during medical training. The results of this questionnaire study, conducted in four medical schools in Sweden after the course in internal medicine (252 respondents; response rate: 74%; median age: 24 years, 61% female), show that 45% and 62% were confident in performing medication reviews and writing medication summary reports, respectively, i.

Identification of Novel Loci Associated With Hip Shape: A Meta-Analysis of Genomewide Association Studies.

We aimed to report the first genomewide association study (GWAS) meta-analysis of dual-energy X-ray absorptiometry (DXA)-derived hip shape, which is thought to be related to the risk of both hip osteoarthritis and hip fracture. Ten hip shape modes (HSMs) were derived by statistical shape modeling using SHAPE software, from hip DXA scans in the Avon Longitudinal Study of Parents and Children (ALSPAC; adult females), TwinsUK (mixed sex), Framingham Osteoporosis Study (FOS; mixed), Osteoporotic Fractures in Men study (MrOS), and Study of Osteoporotic Fractures (SOF; females) (total N = 15,934). Associations were adjusted for age, sex, and ancestry.

HLA and KIR Associations of Cervical Neoplasia.

Background: Cervical cancer is the fourth most common cancer in women, and we recently reported human leukocyte antigen (HLA) alleles showing strong associations with cervical neoplasia risk and protection. HLA ligands are recognized by killer immunoglobulin-like receptors (KIRs) expressed on a range of immune cell subsets, governing their proinflammatory activity. We hypothesized that the inheritance of particular HLA-KIR combinations would increase cervical neoplasia risk.

Mediterranean diet and hip fracture incidence among older adults: the CHANCES project.

Unlabelled: The association between adherence to Mediterranean diet (MD) and hip fracture incidence is not yet established. In a diverse population of elderly, increased adherence to MD was associated with lower hip fracture incidence. Except preventing major chronic diseases, adhering to MD might have additional benefits in lowering hip fracture risk.

Correction: Defining the genetic susceptibility to cervical neoplasia-A genome-wide association study.

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

Burden of hip fracture using disability-adjusted life-years: a pooled analysis of prospective cohorts in the CHANCES consortium.

Background: No studies have estimated disability-adjusted life-years (DALYs) lost due to hip fractures using real-life follow-up cohort data. We aimed to quantify the burden of disease due to incident hip fracture using DALYs in prospective cohorts in the CHANCES consortium, and to calculate population attributable fractions based on DALYs for specific risk factors.

Methods: We used data from six cohorts of participants aged 50 years or older at recruitment to calculate DALYs.

Defining the genetic susceptibility to cervical neoplasia-A genome-wide association study.

A small percentage of women with cervical HPV infection progress to cervical neoplasia, and the risk factors determining progression are incompletely understood. We sought to define the genetic loci involved in cervical neoplasia and to assess its heritability using unbiased unrelated case/control statistical approaches. We demonstrated strong association of cervical neoplasia with risk and protective HLA haplotypes that are determined by the amino-acids carried at positions 13 and 71 in pocket 4 of HLA-DRB1 and position 156 in HLA-B.

Excess mortality after hip fracture in elderly persons from Europe and the USA: the CHANCES project.

Background: Hip fractures are associated with diminished quality of life and survival especially amongst the elderly.

Objective: All-cause mortality after hip fracture was investigated to assess its magnitude.

Methods: A total of 122 808 participants from eight cohorts in Europe and the USA were followed up for a mean of 12.

Burden of Cancer in a Large Consortium of Prospective Cohorts in Europe.

Background: Disability-adjusted life-years (DALYs) are an indicator of mortality, morbidity, and disability. We calculated DALYs for cancer in middle-aged and older adults participating in the Consortium on Health and Ageing Network of Cohorts in Europe and the United States (CHANCES) consortium.

Methods: A total of 90 199 participants from five European cohorts with 10 455 incident cancers and 4399 deaths were included in this study.

Fruit and Vegetable Intake and Hip Fracture Incidence in Older Men and Women: The CHANCES Project.

The role of fruit and vegetable intake in relation to fracture prevention during adulthood and beyond is not adequately understood. We investigated the potential association between fruit and vegetable intake and hip fracture incidence in a large sample of older adults from Europe and the United States. A total of 142,018 individuals (116,509 women) aged ≥60 years, from five cohorts, were followed up prospectively for 1,911,482 person-years, accumulating 5552 hip fractures.

Germline genetics of cancer of unknown primary (CUP) and its specific subtypes.

Cancer of unknown primary site (CUP) is a fatal cancer diagnosed through metastases at various organs. Little is known about germline genetics of CUP which appears worth of a search in view of reported familial associations in CUP. In the present study, samples from CUP patients were identified from 2 Swedish biobanks and a German clinical trial, totaling 578 CUP patients and 7628 regionally matched controls.

Whole-genome sequencing identifies EN1 as a determinant of bone density and fracture.

The extent to which low-frequency (minor allele frequency (MAF) between 1-5%) and rare (MAF ≤ 1%) variants contribute to complex traits and disease in the general population is mainly unknown. Bone mineral density (BMD) is highly heritable, a major predictor of osteoporotic fractures, and has been previously associated with common genetic variants, as well as rare, population-specific, coding variants. Here we identify novel non-coding genetic variants with large effects on BMD (ntotal = 53,236) and fracture (ntotal = 508,253) in individuals of European ancestry from the general population.

Pre-diagnostic vitamin D concentrations and cancer risks in older individuals: an analysis of cohorts participating in the CHANCES consortium.

The associations of circulating 25-hydroxyvitamin D [25(OH)D] concentrations with total and site-specific cancer incidence have been examined in several epidemiological studies with overall inconclusive findings. Very little is known about the association of vitamin D with cancer incidence in older populations. We assessed the association of pre-diagnostic serum 25(OH)D levels with incidence of all cancers combined and incidence of lung, colorectal, breast, prostate and lymphoid malignancies among older adults.