Efficient cross-trait penalized regression increases prediction accuracy in large cohorts using secondary phenotypes
We introduce cross-trait penalized regression (CTPR), a powerful and practical approach for multi-trait polygenic risk prediction in large cohorts. Specifically, we propose a novel cross-trait penalty function with the Lasso and the minimax concave penalty (MCP) to incorporate the shared genetic effects across multiple traits for large-sample GWAS data. Our approach extracts information from the secondary traits that is beneficial for predicting the primary trait based on individual-level genotypes and/or summary statistics.
Disentangling the genetics of lean mass
Lean body mass (LM) plays an important role in mobility and metabolic function. We previously identified five loci associated with LM adjusted for fat mass in kilograms. Such an adjustment may reduce the power to identify genetic signals having an association with both lean mass and fat mass. Our objective was to determine the impact of different fat mass adjustments on genetic architecture of LM and identify additional LM loci.
Common genetic variation in relation to brachial vascular dimensions and flow-mediated vasodilation
Polygenic hazard score, amyloid deposition and Alzheimer's neurodegeneration
Mounting evidence indicates that the polygenic basis of late-onset Alzheimer's disease can be harnessed to identify individuals at greatest risk for cognitive decline. We have previously developed and validated a polygenic hazard score comprising of 31 single nucleotide polymorphisms for predicting Alzheimer's disease dementia age of onset. In this study, we examined whether polygenic hazard scores are associated with: (i) regional tracer uptake using amyloid PET; (ii) regional volume loss using longitudinal MRI; (iii) post-mortem regional amyloid-β protein and tau associated neurofibrillary tangles; and (iv) four common non-Alzheimer's pathologies.
Surgery's role in addressing population health needs
There is a large and unacceptable burden of death and disability from conditions that are treatable by surgery. Several global efforts to address this burden have included the World Health Assembly resolution (WHA68.15) on emergency and essential surgical care, the Lancet Commission on Global Surgery, and the Disease Control Priorities project.
Association studies of up to 1.2 million individuals yield new insights into the genetic etiology of tobacco and alcohol use
Tobacco and alcohol use are leading causes of mortality that influence risk for many complex diseases and disorders. They are heritable and etiologically related behaviors that have been resistant to gene discovery efforts. In sample sizes up to 1.2 million individuals, we discovered 566 genetic variants in 406 loci associated with multiple stages of tobacco use (initiation, cessation, and heaviness) as well as alcohol use, with 150 loci evidencing pleiotropic association.
Outpatient prenteral antimicrobial therapy in vulnerable populations-- people who inject drugs and the homeless
Outpatient parenteral antimicrobial therapy (OPAT) programs can provide high-value care but may be challenging in people who inject drugs (PWID) and homeless individuals. This paper presents a single-center, retrospective, cohort study of adults who received OPAT at an urban, public health hospital from January 1, 2015 to April 30, 2016, grouped by PWID and housing status.
Spot urine sodium-to-potassium ratio is a predictor of stroke
Dietary sodium reduction with concurrent increase in potassium intake is a current public health priority to reduce risk of cardiovascular events. This study explored associations between the spot urine sodium-to-potassium ratio and cardiovascular events in the MESA (Multi-Ethnic Study of Atherosclerosis) longitudinal cohort.
Acquisition of sexually transmitted infections among women using a variety of contraceptive options: A prospective study among high-risk african women
In many African settings, women concurrently face substantial risk of human immunodeficiency virus type 1 (HIV-1) infection, sexually transmitted infections (STIs) and unintended pregnancies. Few studies have evaluated STI risk among users of hormonal implants and copper intrauterine devices (IUDs) although these long-acting reversible contraceptive methods are being promoted widely because of their benefits. Within a prospective study of women at risk for HIV-1, this paper compares the risk of acquisition of Chlamydia trachomatis, Neisseria gonorrhoeae and Trichomonas vaginalis among women using different contraceptive methods.
Clinical diagnoses among individuals with primary age-related tauopathy versus Alzheimer's neuropathology
Primary age-related tauopathy (PART) is increasingly recognized as a pathologic entity distinct from Alzheimer's disease (AD). Given that the diagnosis of PART is an autopsy diagnosis, it is unclear how PART is perceived in clinical practice. Thus, we investigated the presumptive primary and contributing diagnoses in individuals who had cognitive impairment while alive and who met neuropathologic criteria for PART at autopsy. We also compared these clinical diagnoses for people with PART to those with AD neuropathology (ADNP).