Current Genetic Medicine Reports

Purpose of Review: This review describes the clinical features of the major adult-onset genodermatosis-associated hereditary cancer predisposition syndromes. Diagnosis of these conditions can be challenging due to a wide range of clinical features, varied presentations within families and the involvement of multiple medical specialities. Recent Findings: By emphasising the cutaneous and other non-malignant features, we aim to alert clinicians from all specialities to clues in the clinical history which should prompt consideration of a genodermatosis-associated hereditary cancer predisposition syndrome...

PURPOSE OF REVIEW: "Healthy aging" is the state of the aging process in which a person can maintain physical, social, mental, and spiritual wellness. This literature review presents an overview of recent studies that explore how biological, social, and environmental factors contribute to healthy aging. RECENT FINDINGS: A number of genome-wide association studies have been conducted recently for traits related to healthy aging, such as frailty index, healthspan, muscle strength, and parental longevity, leading to the discovery of dozens of genetic variants associated with these traits...

Purpose of Review: Advances in genomic medicine have the potential to revolutionise cancer patient care by driving forwards the clinical practice of precision oncology. This review aims to outline how genomic medicine advances may alter the care of cancer patients and their families over the next 10 years. Recent Findings: The translation of oncogenomic advances into the clinical environment will likely be facilitated by the increasing availability of next-generation sequencing technologies and the increasing genomic literacy of healthcare professionals...

Purpose of Review: SARS-CoV-2, the recently emerged coronavirus (CoV) that is responsible for the current global pandemic Covid-19, first appeared in late 2019 in Wuhan, China. Here, we summarise details of the SARS-CoV-2 genome to assist understanding of the emergence, evolution and diagnosis of this deadly new virus. Recent Findings: Based on high similarities in the genome sequences, the virus is thought to have arisen from SARS-like CoVs in bats but the lack of an intermediate species containing a CoV with even greater similarity has so far eluded discovery...

Purpose of Review: Prostate cancer (PrCa) is the most common cancer in men in the western world and is a major source of morbidity and mortality. Currently, general population PrCa screening is not recommended due to the limitations of the prostate-specific antigen (PSA) test. As such, there is increasing interest in identifying and screening higher-risk groups. The only established risk factors for PrCa are age, ethnicity, and having a family history of PrCa. A significant proportion of PrCa cases are caused by genetic factors...

Purpose of Review: In order to inform patients of their genetic risks, access to the medical records and/or stored samples of their relatives is often helpful. We consider some of the obstacles to such access when these relatives are deceased and suggest how they might be navigated. Recent Findings: We explore an issue first highlighted in 2004 by Lucassen et al. (Br Med J 328:952-953, 2004) and re-evaluate it in the wake of novel technologies and mainstreaming of genomic medicine...

Purpose of the review: Sample size increases have resulted in novel and replicable loci for substance use disorders (SUDs). We summarize some of the latest insights into SUD genetics and discuss some next steps in addiction genetics. Recent findings: Genome-wide association studies have substantiated the role of previously known variants (e.g., rs1229984 in ADH1B for alcohol) and identified several novel loci for alcohol, tobacco, cannabis, opioid and cocaine use disorders...

PURPOSE OF REVIEW: Alcohol use disorder (AUD) is a complex genetic disorder with very high heritability. This polygenic disorder not only results in increased morbidity and mortality, it is also a substantial social and economic burden on families and the nation. For past three decades, several genetic studies were conducted to identify genes and pathways associated with AUD. This review aims to summarize past efforts and recent advances in genetic association studies of AUD and related traits...

Purpose of Review: This review summarises recent advances in the field of epigenetics in order to understand the aetiology of type 2 diabetes (T2D). Recent Findings: DNA methylation at a number of loci has been shown to be robustly associated with T2D, including TXNIP, ABCG1, CPT1A , and SREBF1 . However, due to the cross-sectional nature of many epidemiological studies and predominant analysis in samples derived from blood rather than disease relevant tissues, inferring causality is difficult...

Purpose of Review: We critically evaluate the future potential of machine learning (ML), deep learning (DL), and artificial intelligence (AI) in precision medicine. The goal of this work is to show progress in ML in digital health, to exemplify future needs and trends, and to identify any essential prerequisites of AI and ML for precision health. Recent Findings: High-throughput technologies are delivering growing volumes of biomedical data, such as large-scale genome-wide sequencing assays; libraries of medical images; or drug perturbation screens of healthy, developing, and diseased tissue...

Purpose of Review: Neurodegenerative diseases, neuropsychiatric disorders, and related traits have highly complex etiologies but are also highly heritable and identifying the causal genes and biological pathways underlying these traits may advance the development of treatments and preventive strategies. While many genome-wide association studies (GWAS) have successfully identified variants contributing to polygenic neurodegenerative and neuropsychiatric phenotypes including Alzheimer's disease (AD), schizophrenia (SCZ), and bipolar disorder (BPD) amongst others, interpreting the biological roles of significantly-associated variants in the genetic architecture of these traits remains a significant challenge...

Purpose of review: Over the last decade over 40 loci have been associated with risk of Alzheimer's disease (AD). However, most studies have either focused on identifying risk loci or performing unbiased screens without a focus on protective variation in AD. Here, we provide a review of known protective variants in AD and their putative mechanisms of action. Additionally, we recommend strategies for finding new protective variants. Recent findings: Recent Genome-Wide Association Studies have identified both common and rare protective variants associated with AD...

Purpose of review: In this review we highlight recent advances in the human genetics of frontotemporal dementia (FTD). In addition to providing a broad survey of genes implicated in FTD in the last several years, we also discuss variation in genes implicated in both hereditary leukodystrophies and risk for FTD (e.g., TREM2 , TMEM106B , CSF1R , AARS2 , NOTCH3 ). Recent findings: Over the past five years, genetic variation in approximately 50 genes has been confirmed or suggested to cause or influence risk for FTD and FTD-spectrum disorders...

Purpose of Review: Summarize sex-specific contributors to the genetic architecture of Alzheimer's disease (AD). Recent Findings: There are sex differences in the effects of Apolipoprotein E ( APOE ), genes along the APOE pathway, and genes along the neurotrophic signaling pathway in predicting AD. Reported sex differences are largely driven by stronger associations among females. Evidence also suggests that genetic predictors of amyloidosis are largely shared across sexes, while sex-specific genetic effects emerge downstream of amyloidosis and drive the clinical manifestation of AD...

Purpose of Review: As the costs of genomic testing have fallen, and our understanding of genetic susceptibility to cancers has grown, there has been increasing interest in incorporating testing for cancer susceptibility genes, and polygenic risk estimates, into population cancer screening. A growing body of evidence suggests that this would be both clinically and cost-effective. In this article, we aim to explore the frameworks used to evaluate screening programmes, evaluate whether population screening for cancer susceptibility can be assessed using these standards, and consider additional issues and outcomes of importance in this context...

Purpose of Review: Genomic tests offer increased opportunity for diagnosis, but their outputs are often uncertain and complex; results may need to be revised and/or may not be relevant until some future time. We discuss the challenges that this presents for consent and autonomy. Recent Findings: Popular discourse around genomic testing tends to be strongly deterministic and optimistic, yet many findings from genomic tests are uncertain or unclear. Clinical conversations need to anticipate and potentially challenge unrealistic expectations of what a genomic test can deliver in order to enhance autonomy and ensure that consent to genomic testing is valid...

Purpose of Review: Chronic infection with Helicobacter pylori infection is necessary but not sufficient to initiate development of intestinal-type gastric adenocarcinoma. It is not clear what additional factors tip the scale from commensal bacteria towards a pathogen that facilitates development of gastric cancer. Genetic variants in both the pathogen and host have been implicated, but neither alone explains a substantial portion of disease risk. Recent Findings: In this review, we consider studies that address the important role of human and bacterial genetics, ancestry and their interactions in determining gastric disease risk...

Purpose of Review: This review highlights recent findings regarding genetics of coronary artery calcification (CAC), a marker of subclinical atherosclerosis burden, that is a precursor of clinical coronary artery disease. Recent findings: CAC quantity is heritable. Genome wide association studies of common single nucleotide polymorphisms have identified genomic regions explaining ~2.4% of CAC heritability. Low frequency and rare variants explain additional variation in CAC...

Purpose: Cardiovascular disease (CVD) is the leading cause of death in the United States and globally. There is significant evidence implicating genetic and dietary factors in the development and progression of CVD and its risk factors. Nutritional genomics is a comparatively new field of science that focuses on the relationship of individual genetic variation with response to nutrition. The purpose of this review is to summarize recent progress, in the field of nutritional genomics as it relates to cardiovascular disease...

Purpose of review: Primary mitochondrial disease encompasses an impressive range of inherited energy deficiency disorders having highly variable molecular etiologies as well as clinical onset, severity, progression, and response to therapies of multi-system manifestations. Significant progress has been made in primary mitochondrial disease diagnostic approaches, clinical management, therapeutic options, and preventative strategies that are tailored to major mitochondrial disease phenotypes and subclasses...