Candidate Gene Association Studies Research Articles

Investigation of high gamma-glutamyltransferase syndrome in California Thoroughbred racehorses.

Increases in serum gamma-glutamyltransferase (GGT) activity have been reported in Thoroughbred (TB) racehorses and associated with maladaptation to training but the underlying etiology remains unknown. Classify the etiology of high GGT syndrome in racing TBs by assessment of pancreatic enzymes, vitamin E concentrations, and both a candidate gene and whole genome association study. We hypothesized that a genetic variant resulting in antioxidant insufficiency or pancreatic dysfunction would be responsible for high GGT syndrome in TBs. A total of 138 California racing TBs. Amylase: n=31 affected (serum GGT activity ≥60 IU/L), n=52 control (serum GGT activity <40 IU/L). Lipase: n=19 affected, n=35 control. Serum α-tocopherol concentrations: n=32 affected, n=46 control. Genome-wide association study (GWAS): 36 affected, 58 control. Whole genome sequencing: n=5 affected, n=5 control. Biochemical and vitamin analytes were compared among cohorts. A GWAS was performed and a subset of TBs underwent whole genome sequencing to interrogate candidate genes and positional genetic regions. Serum lipase and amylase activity and α-tocopherol concentrations did not differ between groups. No genetic variants were identified in 2 candidate genes (UGT1A1 and GGT1) that associated with the phenotype. Four single nucleotide polymorphisms (SNPs) approached a suggestive association with the phenotype (P=2.15 × 10-5 ), defining a 100 kb region on chromosome 5 surrounding cluster of differentiation 1a (CD1A1), a transmembrane gene related to the major histocompatibility complex. An underlying genetic etiology may exist for high GGT syndrome in racing TBs, similar to genetic disorders in humans.

A comprehensive meta-analysis and prioritization study to identify vitiligo associated coding and non-coding SNV candidates using web-based bioinformatics tools

Vitiligo is a prevalent depigmentation disorder affecting around 1% of the general population. So far, various Genome Wide Association Studies (GWAS) and Candidate Gene Association Studies (CGAS) have identified several single nucleotide variants (SNVs) as a risk factor for vitiligo. Nonetheless, little has been discerned regarding their direct functional significance to the disease pathogenesis. In this study, we did extensive data mining and downstream analysis using several experimentally validated datasets like GTEx Portal and web tools like rSNPBase, RegulomeDB, HaploReg and STRING to prioritize 13 SNVs from a set of 291SNVs that have been previously reported to be associated with vitiligo. We also prioritized their underlying/target genes and tried annotating their functional contribution to vitiligo pathogenesis. Our analysis revealed genes like FGFR10P, SUOX, CDK5RAP1 and RERE that have never been implicated in vitiligo previously to have strong potentials to contribute to the disease pathogenesis. The study is the first of its kind to prioritize and functionally annotate vitiligo-associated GWAS and CGAS SNVs and their underlying/target genes, based on functional data available in the public domain database.

Network-based meta-analysis and the candidate gene association studies reveal novel ethnicity-specific variants in MFSD3 and MRPL43 associated with dementia with Lewy bodies.

Dementia with Lewy bodies (DLB) is the second most common form of neurodegenerative dementia in elderly people, following Alzheimer's disease. Only three genes, SNCA (α‐synuclein), APOE (apolipoprotein E), and GBA (glucosylceramidase), have been convincingly demonstrated to be associated with DLB. Here, we applied whole‐genome sequencing to blood samples from 61 DLB patients and 45 cognitively normal controls. We used accumulation of candidate mutations to detect novel DLB‐associated genes. Subsequent single nucleotide polymorphism (SNP) genotyping and association studies in a large number of samples from Japanese individuals revealed novel heterozygous variants in MFSD3 (rs143475431, c.888T>A:p.C296*; n = 5,421, p = 0.00063) and MRPL43 (chr10:102746730, c.241A>C:p.N81H; n = 4,782, p = 0.0029). We further found that the MFSD3 variant increased plasma levels of butyrylcholinesterase (n = 1,206, p = 0.029). We believe that our findings will contribute to the understanding of DLB and provide insight into its pathogenic mechanism for future studies.

Host genetic loci LZTFL1 and CCL2 associated with SARS-CoV-2 infection and severity of COVID-19

ObjectivesHost genetic factors contribute to the variable severity of COVID-19. We examined genetic variants from genome-wide association studies and candidate gene association studies in a cohort of patients with COVID-19 and investigated the role of early SARS-CoV-2 strains in COVID-19 severity. MethodsThis case-control study included 123 COVID-19 cases (hospitalized or ambulatory) and healthy controls from the state of Baden-Wuerttemberg, Germany. We genotyped 30 single nucleotide polymorphisms, using a custom-designed panel. Cases were also compared with the 1000 genomes project. Polygenic risk scores were constructed. SARS-CoV-2 genomes from 26 patients with COVID-19 were sequenced and compared between ambulatory and hospitalized cases, and phylogeny was reconstructed. ResultsEight variants reached nominal significance and two were significantly associated with at least one of the phenotypes “susceptibility to infection”, “hospitalization”, or “severity”: rs73064425 in LZTFL1 (hospitalization and severity, P <0.001) and rs1024611 near CCL2 (susceptibility, including 1000 genomes project, P = 0.001). The polygenic risk score could predict hospitalization. Most (23/26, 89%) of the SARS-CoV-2 genomes were classified as B.1 lineage. No associations of SARS-CoV-2 mutations or lineages with severity were observed. ConclusionThese host genetic markers provide insights into pathogenesis and enable risk classification. Variants which reached nominal significance should be included in larger studies.

25 Years of Molecular Psychology: The best is yet to come

This editorial defines the scope of the field of Molecular Psychology, which refers to the study of behavior and its underlying neural systems using the toolset of molecular biology, particularly molecular genetics and epigenetics. It is related to other well-established fields that use molecular tools in animal model organisms (Behavioral Neuroscience; Neuroethology) or that focus on molecular mechanisms of human mental health and disease (Molecular Psychiatry; Health Psychology), but extends beyond these fields by its inclusion of broad domains of human behavior; the precise molecular mechanisms by which environmental exposure and experiences modify gene expression; and the ethical, legal, and social implications (ELSI) of these discoveries. Considering the first 25 years of studies that included candidate gene and genome-wide association studies, I suggest a roadmap for the next decade of work. On the launch of F1000 Molecular Psychology: Brain, Behavior &amp; Society, I hope this publication platform will become instrumental in growing this field by promoting a spirit of support and community among its practitioners, embracing transparency and rigor, and publishing novel ideas and studies ranging from pilot and proof-of-concept first steps to gold-standard definitive milestones.

Novel brown adipose tissue candidate genes predicted by the human gene connectome

Brown adipose tissue (BAT) is a promising therapeutic target against obesity. Therefore, research on the genetic architecture of BAT could be key for the development of successful therapies against this complex phenotype. Hypothesis-driven candidate gene association studies are useful for studying genetic determinants of complex traits, but they are dependent upon the previous knowledge to select candidate genes. Here, we predicted 107 novel-BAT candidate genes in silico using the uncoupling protein one (UCP1) as the hallmark of BAT activity. We first identified the top 1% of human genes predicted by the human gene connectome to be biologically closest to the UCP1, estimating 167 additional pathway genes (BAT connectome). We validated this prediction by showing that 60 genes already associated with BAT were included in the connectome and they were biologically closer to each other than expected by chance (p < 2.2 × 10−16). The rest of genes (107) are potential candidates for BAT, being also closer to known BAT genes and more expressed in BAT biopsies than expected by chance (p < 2.2 × 10−16; p = 4.39 × 10–02). The resulting new list of predicted human BAT genes should be useful for the discovery of novel BAT genes and metabolic pathways.

The impact of ADHD genetic risk on educational achievement: a comparative cross-national study

Abstract Human capital accumulation is a key driver of economic development across countries. Although previous studies have shown that country-specific circumstances (e.g., cultural, health-related, and educational factors) are strongly related with the accumulation of human capital in society, few studies have explored the importance of innate ability factors in general and ADHD-related behavioral symptoms in particular for cognitive skill outcomes. This paper hypothesizes and empirically establishes the educational burden of the ADHD-related behavioral symptoms on aggregate cognitive achievement outcomes. We use a novel compilation of the 2- and 7-repeat allele variants of the human DRD4 exon III gene that candidate gene association studies have identified as an important biomarker in the etiology of childhood ADHD. We find that our indicator for the prevalence of ADHD genetic risk in society has a negative and statistically significant impact on educational achievement. Additional sensitivity tests and estimation methods further corroborate our main hypothesis.

A systematic review and functional bioinformatics analysis of genes associated with Crohn\u2019s disease identify more than 120 related genes

BackgroundCrohn’s disease is one of the two categories of inflammatory bowel diseases that affect the gastrointestinal tract. The heritability estimate has been reported to be 0.75. Several genes linked to Crohn’s disease risk have been identified using a plethora of strategies such as linkage-based studies, candidate gene association studies, and lately through genome-wide association studies (GWAS). Nevertheless, to our knowledge, a compendium of all the genes that have been associated with CD is lacking.MethodsWe conducted functional analyses of a gene set generated from a systematic review where genes potentially related to CD found in the literature were analyzed and classified depending on the genetic evidence reported and putative biological function. For this, we retrieved and analyzed 2496 abstracts comprising 1067 human genes plus 22 publications regarding 133 genes from GWAS Catalog. Then, each gene was curated and categorized according to the type of evidence associated with Crohn’s disease.ResultsWe identified 126 genes associated with Crohn’s disease risk by specific experiments. Additionally, 71 genes were recognized associated through GWAS alone, 18 to treatment response, 41 to disease complications, and 81 to related diseases. Bioinformatic analysis of the 126 genes supports their importance in Crohn’s disease and highlights genes associated with specific aspects such as symptoms, drugs, and comorbidities. Importantly, most genes were not included in commercial genetic panels suggesting that Crohn’s disease is genetically underdiagnosed.ConclusionsWe identified a total of 126 genes from PubMed and 71 from GWAS that showed evidence of association to diagnosis, 18 to treatment response, and 41 to disease complications in Crohn’s disease. This prioritized gene catalog can be explored at http://victortrevino.bioinformatics.mx/CrohnDisease.

Systematic review and meta-analysis of candidate gene association studies of benign prostate hyperplasia

BackgroundBenign prostate hyperplasia (BPH) is the most common urological problem in elderly males. Recent studies have reported polymorphism in various metabolic genes in BPH. However, their association with the susceptibility of BPH is still inconsistent. Here, we systematically reviewed and performed a meta-analysis of CYP17, VDR, and ACE genes to determine their precise association with the risk of BPH.MethodsA comprehensive literature search for published studies on candidate gene associations involving vitamin D receptor (VDR), angiotensin-converting enzyme (ACE), and CYP17 genes with the risk of BPH was done up to April 2020 in PubMed, Scopus, Cochrane Central Register of Controlled Trials (CENTRAL), and Google Scholar databases. Fixed/random effects models were used to estimate the odd’s ratio (OR) and 95% confidence intervals (CIs). Begg’s funnel plot was used to assess the potential for publication bias.ResultsWe found a total of 23 studies containing 3461 cases and 3833 controls for these gene polymorphisms. A significant association of ACE gene polymorphism was observed under the recessive (II vs. ID + DD) model for BPH susceptibility compared to control subjects (overall OR = 1.67, 95% CI = 1.03–2.73). Similar trends were observed for ACE gene polymorphism in Caucasian (OR = 6.18, 95% CI = 1.38–27.68) and Asian (OR = 1.42, 95% CI = 0.99–2.03) populations under study. No significant association was observed in VDR and CYP17 gene polymorphisms in any dominant or recessive models.ConclusionSignificant OR demonstrated the implication of ACE gene polymorphism in the proliferation of prostate tissue, which in turn is associated with BPH susceptibility. However, prospective studies at large scale and sample size are needed to confirm the current findings.

Genetic variants of PKLR are associated with acute pain in sickle cell disease

AbstractAcute pain, the most prominent complication of sickle cell disease (SCD), results from vaso-occlusion triggered by sickling of deoxygenated red blood cells (RBCs). Concentration of 2,3-diphosphoglycerate (2,3-DPG) in RBCs promotes deoxygenation by preferentially binding to the low-affinity T conformation of HbS. 2,3-DPG is an intermediate substrate in the glycolytic pathway in which pyruvate kinase (gene PKLR, protein PKR) is a rate-limiting enzyme; variants in PKLR may affect PKR activity, 2,3-DPG levels in RBCs, RBC sickling, and acute pain episodes (APEs). We performed a candidate gene association study using 2 cohorts: 242 adult SCD-HbSS patients and 977 children with SCD-HbSS or SCD-HbSβ0 thalassemia. Seven of 47 PKLR variants evaluated in the adult cohort were associated with hospitalization: intron 4, rs2071053; intron 2, rs8177970, rs116244351, rs114455416, rs12741350, rs3020781, and rs8177964. All 7 variants showed consistent effect directions in both cohorts and remained significant in weighted Fisher's meta-analyses of the adult and pediatric cohorts using P < .0071 as threshold to correct for multiple testing. Allele-specific expression analyses in an independent cohort of 52 SCD adults showed that the intronic variants are likely to influence APE by affecting expression of PKLR, although the causal variant and mechanism are not defined.

Genetics in the ADHD Clinic: How Can Genetic Testing Support the Current Clinical Practice?

Attention-deficit/hyperactivity disorder (ADHD) is a neurodevelopmental disorder with a childhood prevalence of 5%. In about two-thirds of the cases, ADHD symptoms persist into adulthood and often cause significant functional impairment. Based on the results of family and twin studies, the estimated heritability of ADHD approximates 80%, suggests a significant genetic component in the etiological background of the disorder; however, the potential genetic effects on disease risk, symptom severity, and persistence are unclear. This article provides a brief review of the genome-wide and candidate gene association studies with a focus on the clinical aspects, summarizing findings of ADHD disease risk, ADHD core symptoms as dimensional traits, and other traits frequently associated with ADHD, which may contribute to the susceptibility to other comorbid psychiatric disorders. Furthermore, neuropsychological impairment and measures from neuroimaging and electrophysiological paradigms, emerging as potential biomarkers, also provide a prominent target for molecular genetic studies, since they lie in the pathway from genes to behavior; therefore, they can contribute to the understanding of the underlying neurobiological mechanisms and the interindividual heterogeneity of clinical symptoms. Beyond the aforementioned aspects, throughout the review, we also give a brief summary of the genetic results, including polygenic risk scores that can potentially predict individual response to different treatment options and may offer a possibility for personalized treatment for the therapy of ADHD in the future.

A genome-wide association study of outcome from traumatic brain injury.

SummaryBackgroundFactors such as age, pre-injury health, and injury severity, account for less than 35% of outcome variability in traumatic brain injury (TBI). While some residual outcome variability may be attributable to genetic factors, published candidate gene association studies have often been underpowered and subject to publication bias.MethodsWe performed the first genome- and transcriptome-wide association studies (GWAS, TWAS) of genetic effects on outcome in TBI. The study population consisted of 5268 patients from prospective European and US studies, who attended hospital within 24 h of TBI, and satisfied local protocols for computed tomography.FindingsThe estimated heritability of TBI outcome was 0·26. GWAS revealed no genetic variants with genome-wide significance (p < 5 × 10−8), but identified 83 variants in 13 independent loci which met a lower pre-specified sub-genomic statistical threshold (p < 10−5). Similarly, none of the genes tested in TWAS met tissue-wide significance. An exploratory analysis of 75 published candidate variants associated with 28 genes revealed one replicable variant (rs1800450 in the MBL2 gene) which retained significance after correction for multiple comparison (p = 5·24 × 10−4).InterpretationWhile multiple novel loci reached less stringent thresholds, none achieved genome-wide significance. The overall heritability estimate, however, is consistent with the hypothesis that common genetic variation substantially contributes to inter-individual variability in TBI outcome. The meta-analytic approach to the GWAS and the availability of summary data allows for a continuous extension with additional cohorts as data becomes available.FundingA full list of funding bodies that contributed to this study can be found in the Acknowledgements section.

Genetic and epigenetic studies in non-syndromic oral clefts.

The etiology of non-syndromic oral clefts (NSOFC) is complex with genetics, genomics, epigenetics, and stochastics factors playing a role. Several approaches have been applied to understand the etiology of non-syndromic oral clefts. These include linkage, candidate gene association studies, genome-wide association studies, whole-genome sequencing, copy number variations, and epigenetics. In this review, we shared these approaches, genes, and loci reported in some studies.

Polygenic risk impacts PDGFRA mutation penetrance in non-syndromic cleft lip and palate.

Non-syndromic cleft lip with or without cleft palate (NSCL/P) is a common, severe craniofacial malformation that imposes significant medical, psychosocial and financial burdens. NSCL/P is a multifactorial disorder with genetic and environmental factors playing etiologic roles. Currently, only 25% of the genetic variation underlying NSCL/P has been identified by linkage, candidate gene and genome-wide association studies. In this study, whole-genome sequencing and genome-wide genotyping followed by polygenic risk score (PRS) and linkage analyses were used to identify the genetic etiology of NSCL/P in a large three-generation family. We identified a rare missense variant in PDGFRA (c.C2740T; p.R914W) as potentially etiologic in a gene-based association test using pVAAST (P = 1.78×10-4) and showed decreased penetrance. PRS analysis suggested that variant penetrance was likely modified by common NSCL/P risk variants, with lower scores found among unaffected carriers. Linkage analysis provided additional support for PRS-modified penetrance, with a 7.4-fold increase in likelihood after conditioning on PRS. Functional characterization experiments showed that the putatively causal variant was null for signaling activity in vitro; further, perturbation of pdgfra in zebrafish embryos resulted in unilateral orofacial clefting. Our findings show that a rare PDGFRA variant, modified by additional common NSCL/P risk variants, have a profound effect on NSCL/P risk. These data provide compelling evidence for multifactorial inheritance long postulated to underlie NSCL/P and may explain some unusual familial patterns.

Neurobiological Correlates of Fatherhood During the Postpartum Period: A Scoping Review.

During the postpartum period, the paternal brain suffers extensive and complex neurobiological alterations, through the experience of father–infant interactions. Although the impact of such experience in the mother has been increasingly studied over the past years, less is known about the neurobiological correlates of fatherhood—that is, the alterations in the brain and other physiological systems associated with the experience of fatherhood. With the present study, we aimed to perform a scoping review of the available literature on the genetic, neuroendocrine, and brain correlates of fatherhood and identify the main gaps in the current knowledge. PubMed, Scopus, and Web of Science electronic databases were searched for eligible studies on paternal neuroplasticity during the postpartum period, over the past 15 years. Reference lists of relevant key studies and reviews were also hand-searched. The research team independently screened the identified studies based on the established inclusion criteria. Extracted data were analyzed using tables and descriptive synthesis. Among the 29 studies that met our inclusion criteria, the vast majority pertained to neuroendocrine correlates of fatherhood (n = 19), followed by brain activity or connectivity (n = 7), association studies of candidate genes (n = 2), and brain structure correlates (n = 1). Collectively, studies published during the past 15 years suggest the existence of significant endocrine (testosterone, oxytocin, prolactin, and cortisol levels) and neurofunctional alterations (changed activity in several brain networks related to empathy and approach motivation, emotional processing and mentalizing, emotion regulation, dorsal attention, and default mode networks) as a result of fatherhood, as well as preliminary evidence of genetic variability accounting for individual differences during the postpartum period in fathers. No studies were so far published evaluating epigenetic mechanisms associated with the paternal brain, something that was also the focus of the current review. We highlight the need for further research that examines neuroplasticity during the experience of fatherhood and that considers both the interplay between hormones and simultaneous assessment of the different biomarkers (e.g., associations between hormones and neural activity); data collection protocols and assessment times should also be refined.

TaNRT2.1-6B is a dual-affinity nitrate transporter contributing to nitrogen uptake in bread wheat under both nitrogen deficiency and sufficiency

Multiple nitrate transporter (NRT) genes exist in the genome of bread wheat, and it is of great importance to identify the elite NRT genes for N-efficient wheat cultivar breeding. A candidate gene association study (CGAS) of six N use efficiency (NUE) related traits (grain N concentration (GNC), straw N concentration (SNC), grain yield (GY), grain N accumulation (GNA), shoot total N accumulation (STN) and N harvest index (NHI)) was performed based on SNPs in 46 NRT2 genes using a panel composed of 286 wheat cultivars. CGAS identified TaNRT2.1-6B as an elite NRT gene that is significantly associated with four (NHI, SNC, GNA and GY) of the six NUE-related traits simultaneously. TaNRT2.1-6B is located on the plasma membrane and acts as a dual-affinity NRT. The overexpression of TaNRT2.1-6B increased the N influx and root growth of wheat, whereas gene silence lines resulted in the opposite effects. The overexpression of TaNRT2.1-6B also improved GY and N accumulation of wheat under either limited or sufficient N conditions. The data provide the TaNRT2.1-6B gene and the two associated SNP markers as promising powerful tools for breeding wheat cultivars with high N uptake ability and NUE.

Complementary Experimental Methods in Genetics Open Up New Avenues of Research to Elucidate the Pathogenesis of Periodontitis.

A complex disease such as periodontitis is the sum of environmental and genetic effects. The personal genetic constitution interacts with the effects of internal and external risk factors like smoking, oral hygiene, malnutrition, emotional stress, and age. Accordingly, individuals who live in the same environmental context and share comparable lifestyle habits have different disease risks. Genetic research offers the identification of DNA sequence variants that have a causal role in disease etiology and allows the identification of disease relevant immune and metabolic pathways that contribute to disease susceptibility and pathogenesis in specific situations. Real advances have been made in genetic medical research in the last years. Starting from candidate gene association studies, new approaches were employed that have expanded the study design of genomewide association studies to genomewide meta-analyses and gene x environment interaction studies. Cost efficient whole-exome and whole-genome sequencing of patients with rare severe forms of periodontitis has the potential to identify genes and pathways with a direct role in the pathogenesis of common forms. In parallel, animal models were developed that use genetically highly diverse mouse lines to identify risk genes of human diseases. This chapter presents the main studies and the identified susceptibility genes that have clear statistical evidence. In addition, it describes pioneering studies that used advanced methods in experimental dental research, opening up new avenues of research. Although the knowledge of the genetic architecture of periodontitis is still in its infancy, genetic research is building the basis for future works with the potential to advance dental medicine in ways that will determine the various causes of periodontal diseases. This knowledge may eventually allow making predictions about disease risk for individual patients and leading to diagnosis and treatments that do not treat the symptoms but heal the disease.

Chapter 19 - Genetics in aphasia recovery

Considerable research efforts have been exerted toward understanding the mechanisms underlying recovery in aphasia. However, predictive models of spontaneous and treatment-induced recovery remain imprecise. Some of the hitherto unexplained variability in recovery may be accounted for with genetic data. A few studies have examined the effects of the BDNF val66met polymorphism on aphasia recovery, yielding mixed results. Advances in the study of stroke genetics and genetics of stroke recovery, including identification of several susceptibility genes through candidate-gene or genome-wide association studies, may have implications for the recovery of language function. The current chapter discusses both the direct and indirect evidence for a genetic basis of aphasia recovery, the implications of recent findings within the field, and potential future directions to advance understanding of the genetics-recovery associations.

The Need to Shift Pharmacogenetic Research from Candidate Gene to Genome-Wide Association Studies

The primary research approach in pharmacogenetics has been candidate gene association studies (CGAS), but pharmacogenomic genome-wide association studies (GWAS) are becoming more common. We are now at a critical juncture when the results of those two research approaches, CGAS and GWAS, can be compared in pharmacogenetics. We analyzed publicly available databases of pharmacogenetic CGAS and GWAS (i.e., the Pharmacogenomics Knowledgebase [PharmGKB®] and the NHGRI-EBI GWAS catalog)and the vast majority of variants (98%) and genes (94%) discovered in pharmacogenomic GWAS were novel (i.e., not previously studied CGAS). Therefore, pharmacogenetic researchers are not selecting the right candidate genes in the vast majority of CGAS, highlighting a need to shift pharmacogenetic research efforts from CGAS to GWAS.

Host genetic factors determining COVID-19 susceptibility and severity.

The COVID-19 pandemic caused by the Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) poses an unprecedented challenge to humanity. SARS-CoV-2 infections range from asymptomatic to severe courses of COVID-19 with acute respiratory distress syndrome (ARDS), multiorgan involvement and death. Risk factors for disease severity include older age, male sex, increased BMI and pre-existing comorbidities. Ethnicity is also relevant to COVID-19 susceptibility and severity. Host genetic predisposition to COVID-19 is now increasingly recognized and whole genome and candidate gene association studies regarding COVID-19 susceptibility have been performed. Several common and rare variants in genes related to inflammation or immune responses have been identified. We summarize research on COVID-19 host genetics and compile genetic variants associated with susceptibility to COVID-19 and disease severity. We discuss candidate genes that should be investigated further to understand such associations and provide insights relevant to pathogenesis, risk classification, therapy response, precision medicine, and drug repurposing.