Objectives: To identify clinically actionable genetic variants from targeted sequencing of 68 disease-related genes, estimate their penetrance, and assess the impact of disclosing results to participants and providers. Patients and Methods: The Return of Actionable Variants Empirical (RAVE) Study investigates outcomes following the return of pathogenic/likely pathogenic (P/LP) variants in 68 disease-related genes. The study was initiated in December 2016 and is ongoing. Targeted sequencing was performed in 2533 individuals with hyperlipidemia or colon polyps. The electronic health records (EHRs) of participants carrying P/LP variants in 36 cardiovascular disease (CVD) genes were manually reviewed to ascertain the presence of relevant traits. Clinical outcomes, health care utilization, family communication, and ethical and psychosocial implications of disclosure of genomic results are being assessed by surveys, telephone interviews, and EHR review. Results: Of 29,208 variants in the 68 genes, 1915 were rare (frequency <1%) and putatively functional, and 102 of these (60 in 36 CVD genes) were labeled P/LP based on the American College of Medical Genetics and Genomics framework. Manual review of the EHRs of participants (n=73 with P/LP variants in CVD genes) revealed that 33 had the expected trait(s); however, only 6 of 45 participants with non–familial hypercholesterolemia (FH) P/LP variants had the expected traits. Conclusion: Expected traits were present in 13% of participants with P/LP variants in non-FH CVD genes, suggesting low penetrance; this estimate may change with additional testing performed as part of the clinical evaluation. Ongoing analyses of the RAVE Study will inform best practices for genomic medicine.

Dementia, a disabling syndrome of the elderly characterized by the decline in memory and cognition, is increasing in incidence and affects not only the individual but also their family and close ones. Hyperthyroidism can mimic many other diseases and untreated hyperthyroidism can lead to adverse problems of various systems including the heart, bones, muscles, menstrual cycle, and fertility. In this article, we have tried to evaluate the association between hyperthyroidism and dementia, as well as the impact of hyperthyroidism management in the treatment and prevention of dementia. Studies available in the PubMed database have been used, excluding animal studies and including studies of adults above the age of 50. The analysis of studies reveals that thyroid dysfunction can lead to cognitive impairment. It has not been able to prove that hyperthyroidism can lead to an earlier onset of dementia. But subclinical hyperthyroidism, thyroid-stimulating hormone (TSH) levels below the normal range, and high free thyroxine (T4) levels increase the risk of dementia among the elderly. The possible mechanisms involved in this association have also been discussed. Thus, we concluded that it is essential to detect and manage hyperthyroidism at an earlier stage since hyperthyroidism increases the risk of dementia. The possibility of using antithyroid treatment in euthyroid dementia is yet to be studied extensively.

We investigated monogenic and polygenic causes of hypercholesterolemia in a population-based cohort, excluding secondary hypercholesterolemia, and using an established framework to identify pathogenic variants. We studied 1682 individuals (50.2 ± 8.6 years, 41.3% males) from southeast Minnesota with primary hypercholesterolemia (low-density lipoprotein cholesterol (LDL-C) ≥155 mg/dl in the absence of identifiable secondary causes). Familial hypercholesterolemia (FH) phenotype was defined as a Dutch Lipid Clinic Network (DLCN) score ≥6. Participants underwent sequencing of LDLR, APOB, and PCSK9, and genotyping of 12 LDL-C-associated single-nucleotide variants to construct a polygenic score (PGS) for LDL-C. The presence of a pathogenic/likely pathogenic variant was considered monogenic etiology and a PGS ≥90th percentile was considered polygenic etiology. The mean LDL-C level was 187.3 ± 32.3 mg/dl and phenotypic FH was present in 8.4% of the cohort. An identifiable genetic etiology was present in 17.1% individuals (monogenic in 1.5% and polygenic in 15.6%). Phenotypic and genetic FH showed poor overlap. Only 26% of those who met the clinical criteria of FH had an identifiable genetic etiology and of those with an identifiable genetic etiology only 12.9% met clinical criteria for FH. Genetic factors explained 7.4% of the variance in LDL-C. In conclusion, in adults with primary hypercholesterolemia, 17.1% had an identifiable genetic etiology and the overlap between phenotypic and genetic FH was modest.

Polycystic ovarian syndrome (PCOS) is the most common endocrine disorder in reproductive-age women that causes infertility. Obesity and insulin resistance are closely tied to the pathophysiology of PCOS. Current first-line treatments include lifestyle modifications, hormone modulators, and laparoscopic ovarian drilling, but little attention has been given to bariatric surgery as a viable option. A detailed review of the literature regarding the outcomes of obese women with PCOS after bariatric surgery is necessary. All studies were found in the PubMed database, limited to females and humans, and selected due to relevancy and quantitative data. Bariatric surgery promotes significant weight loss within one year, which is associated with amelioration of insulin resistance, hyperandrogenism, menstrual irregularity, and ovulatory dysfunction. Surgery successfully mediates the regression of PCOS and promotes successful pregnancy. Thus, we recommend the consideration of bariatric surgery as part of the main treatment considerations in obese patients with PCOS. However, more focused and comprehensive research with better study designs are still needed in the future to investigate PCOS and bariatric surgery.

Vitamin K (VK) has an established biological function in blood coagulation and hemostasis and maintains general health and bone wellbeing. VK supplements have been promoted to treat and prevent many diseases, particularly for decreasing fracture risk in osteoporosis, a chronic condition described by weak bone tissue, and a high fracture risk following minor trauma. It affects older people from different races and ethnicity, mainly postmenopausal women. Many kinds of research emphasize the role of VK in improving bone health and preventing osteoporotic bone fracture, but the findings are mostly inconclusive. In this literature review, PubMed and Google Scholar databases were used as the primary sources to select the relevant studies and review the association between VK and bone health and also, to explore the impact of VK supplementation in osteoporosis management. A majority of studies reported that VK has an essential role in promoting bone health. Although some studies revealed that VK might increase bone mineral density and reduce fracture risk in people with osteoporosis, VK supplements' potential benefits were not sufficiently supported. Thus, more clinical studies are needed to determine the positive effects of VK supplementation in osteoporosis prevention and treatment.