Genetic Influences Research Articles

Causal role of immune cells in muscle atrophy: mendelian randomization study

Immune system and inflammation had a great influence on the progression of muscle atrophy. However, the causal relationship with specific immune cell traits remained uncertain. The aim of this study was to elucidate the genetic influences on these associations, providing insights into the underlying mechanisms of muscle atrophy. A bidirectional two-sample Mendelian randomization (MR) analysis was conducted to investigate the causal relationship between immune cell phenotypes and muscle atrophy. Data on immune cell phenotypes were obtained from a research cohort containing data on 731 immune cell phenotypes and data on muscle atrophy were sourced from a Finnish database. MR analysis was performed using the MR-Egger method, weighted median, inverse variance weighting, heterogeneity testing, sensitivity analysis, and multiplicity analysis, with results subjected to false discovery rate(FDR) correction. Additionally, the UK Biobank cohort was utilized as an external validation. A total of 31 immune phenotypes with causal relationships with muscle atrophy were identified, including various phenotypes of conventional dendritic cells, myeloid cells, T cells/B cells/natural killer cells, regulatory cells, and T cell maturation stages. Among them, 12 immune phenotypes were identified as exhibiting a positive causal relationship with muscle atrophy, while 19 immune phenotypes were demonstrated to have a negative causal association, highlighting the complex interactions between immune cells and muscle health. The results of the reverse MR analysis indicated that a negative correlation between muscle atrophy and CD28 on secreting Treg (OR = 0.9038, 95%CI:0.8308 ~ 0.9832, P = 0.0186). A significant positive correlation was revealed by external datasets between the CD25 on IgD + CD38- immune phenotype and the risk of muscle atrophy, which was consistent with the trend observed in the training group (OR = 1.1041, 95% CI: 1.1005–1.1076, P = 0.0263). No evidence of pleiotropy was observed, and the reliability of these findings was demonstrated by the leave-one-out analysis. The findings highlight significant correlations between certain immune cell features and muscle atrophy, providing potential targets for further investigation of immunological mechanisms and therapeutic interventions for this condition.

Genetic Diversity and Forensic Utility of X-STR Loci in Punjabi and Kashmiri Populations: Insights into Population Structure and Ancestry

Background: X-chromosomal short tandem repeats (X-STRs) are crucial in forensic applications, particularly in complex kinship cases, and play an important role in population genetics. However, there is limited data on X-STR variation in Pakistani populations, especially among ethnic groups like Kashmiri and Punjabi. Methodology: This study investigates the forensic and genetic properties of 12 X-STRs from the Investigator Argus X-12 Kit (QIAGEN, Hilden, Germany) in 125 families (75 Kashmiri, 50 Punjabi) from Azad Jammu and Kashmir and Punjab, Pakistan. Results: In both populations, a total of 222 alleles were identified across the 12 X-STR loci (Punjabi 171 alleles, Kashmiri 161 alleles), with allele frequencies ranging from 0.0056 to 0.3033. DXS10148 was the most polymorphic locus with 28 alleles, while DXS7132 was the least polymorphic with 9 alleles. Most loci were in linkage equilibrium, except for the DXS10135/DXS10148 pair in males, with no loci exhibiting significant linkage disequilibrium in females. The combined power of discrimination was 0.999 999 9977 for Kashmiri males, 0.999 999 999 999 9746 for Kashmiri females, and 0.999 999 999 999 9781 for Punjabi females. In Kashmiri males, 34, 31, 28, and 32 haplotypes were observed across the four linkage groups (LG1, LG2, LG3, and LG4), though these groups did not form stable haplotypes, as indicated by Linkage Equilibrium within and significant Linkage Disequilibrium between groups. Conclusions: Genetic structure analysis using Principal Component Analysis and STRUCTURE revealed distinct clustering patterns for the Kashmiri and Punjabi populations, indicating unique genetic backgrounds and ancestry influences, particularly distinguishing them from East Asian populations. This study provides a comprehensive analysis of X-STR variation in Punjabi and Kashmiri populations, offering valuable insights for forensic and population genetic studies.

Common Genetic Influence on the Relationship Between Gaming Addiction and Attention Deficit Hyperactivity Disorder in Young Adults: A Twin Study.

Although the relationship between gaming addiction (GA) and attention deficit hyperactivity disorder (ADHD) is well established, the causal mechanism of this relationship remains ambiguous. We aimed to investigate whether common genetic and/or environmental factors explain the GA-ADHD relationship. We recruited 1413 South Korean adult twins (837 monozygotic [MZ], 326 same-sex dizygotic [DZ], and 250 opposite-sex DZ twins; mean age = 23.1 ± 2.8 years) who completed an online survey on GA and related traits. Correlational analysis and bivariate model-fitting analysis were conducted. Phenotypic correlation between GA and ADHD in the present sample was 0.55 (95% CI [0.51, 0.59]). Bivariate model-fitting analysis revealed that genetic variances were 69% (95% CI [64%, 73%]) and 68% (95% CI [63%, 72%]) for ADHD and GA respectively. The remaining variances (ADHD: 31%; GA: 32%) were associated with nonshared environmental variances, including measurement error. Genetic and nonshared environmental correlations between ADHD and GA were 0.68 (95% CI [0.62, 0.74]) and 0.22 (95% CI [0.13, 0.30]) respectively, which indicates that shared genes can explain 82% of the phenotypic correlation between ADHD and GA. Our study demonstrated that the ADHD-GA association was largely due to shared genetic vulnerability.

Attention-mediated genetic influences on psychotic symptomatology in adolescence

Attention-mediated genetic influences on psychotic symptomatology in adolescence

Impact of Genetic and Environmental Factors on Peripheral Refraction.

Investigate genetic and environmental influences on refractive errors in monozygotic (MZ) and dizygotic (DZ) twin pairs. We assessed foveal and peripheral refractions in 54 MZ and 46 DZ twins, capturing three scans across the retina. The study focused on spherical equivalent (M) at the fovea (MLOS) and changes in midperipheral (δMmid-periphery), and peripheral (δMperiphery) defocus, along with nasal-temporal asymmetry (root mean squared error [RMSEASY]) and image shell contour (RMSEAVG). Genetic and environmental contributions were analyzed using structural equation models. No significant differences were observed between MZ and DZ twins for the examined variables. Intraclass correlations (ICC) indicated an important difference in genetic influence between MLOS, with the MZ twin pairs showing a higher correlation (0.83) than DZ (0.69) pairs, and δMperiphery, because the ICC for the MZ doubled (0.87) that of the DZ (0.42) pairs. Heritability estimates from the ACE model confirmed the large difference on genetic factors' influence on the variance for MLOS (0.13) and δMperiphery (0.77) change in refractive error. RMSEASY and RMSEAVG metrics showed significant genetic impact, particularly pronounced in the peripheral measurements, revealing high genetic control. The study delineates a marked environmental impact on central refractive errors, whereas genetic factors had a more significant influence on peripheral refractive variance and retinal image traits. Findings of the ACE model highlight the intricate genetic and environmental interplay in refractive error development, with a notable genetic dominance in peripheral vision characteristics. This suggests potential genetic targets for interventions in myopia management and emphasizes the need for personalized approaches based on genetic predispositions. Understanding the impact of genetics and environment on peripheral refraction is essential for deepening our fundamental knowledge of myopia and guiding the development of advanced myopia control strategies.

Longitudinal Analysis of Sweet Taste Preference Through Genetic and Phenotypic Data Integration

Understanding the genetic basis of sweet taste preference is crucial for potential implications in diet-related health outcomes, such as obesity. This study identified genes and single nucleotide polymorphisms (SNPs) associated with sweet taste preferences over time. Data from the American Nurses’ Health Study (NHS1) and Health Professionals Follow-up Study (HPFS) cohorts were analyzed. Using tools like PLINK and METAL for genetic associations and FUMA for functional annotation, the study identified eight SNPs associated with sweet taste preferences. Notably, rs80115239 and rs12878143 were identified as key determinants of the highest and lowest associations with sweet taste preferences, respectively. Individuals with the rs80115239 (AA) genotype displayed a higher preference for sweet tastes, including chocolate and cake, but a lower preference for physical activity, fruits, and vegetables, particularly in females from the NHS1 cohort, linking this genotype to a higher obesity risk. Conversely, those with the rs12878143 (CC) genotype preferred fruits, vegetables, coffee, and tea, with a lower preference for sweetened beverages, but the correlation with obesity risk was less clear due to inconsistent data. In conclusion, these findings highlight the genetic influences on sweet taste preference and their potential role in personalized dietary recommendations and obesity management strategies.

THE CORRELATION BETWEEN PHYSICAL ACTIVITY, EMOTIONAL EATING, EATING PATTERN, AND GENETIC TRAITS WITH OBESITY AMONG FEMALE STUDENTS

ABSTRACTBackground: The prevalence of obesity continues to rise steadily due to various factors. The demanding academic schedules leads to reduced physical activities among female students. Academic stress may induce emotional instability, which may result in emotional eating. Excessive food intake may ultimately contribute to the development of obesity.Objectives: This study aims to analyse factors contributing to obesity in female students, such as physical activity, emotional eating, eating pattern, and genetic traits. Methods: Employing a cross-sectional research design, was conducted at Jenderal Sudirman University in October 2022. A sample comprising 54 female students was selected through a stratified random sampling technique. Research instruments were International Physical Activity Questionnaire-Short Form (IPAQ-SF) to assess physical activity levels, the Emotional Eating Scale (SSES) to gauge emotional eating tendencies, the Food Frequency Questionnaire (FFQ) to evaluate dietary patterns, and a genetic questionnaire to ascertain genetic antecedents. The bivariate analysis between variables were conducted using Chi-Square test.Results: There is a statistically significant correlation between emotional eating behaviors and the prevalence of obesity (p=0.028). Furthermore, a statistically significant association is observed between genetic factors and the incidence of obesity (p=0.000). In contrast, no statistically significant relationships are discerned between obesity and physical activity (p=0.386), high-energy dietary patterns (p=0.268), or low-energy dietary patterns (p=0.102). Conclusion: This investigation substantiates the presence of a relationship between emotional eating tendencies and genetic factors with the manifestation of obesity among the studied population. Conversely, no discernible relationships were identified between physical activity, dietary patterns, and obesity. These findings underscore the multifaceted nature of obesity etiology and highlight the prominence of emotional and genetic influences in this context.Keywords: Eating pattern; Emotional Eating; Genetic, Obesity; Physical Activity

Understanding the Etiopathogenesis of Cardiomyopathies: New Insights

Background Cardiomyopathy, a rare heart disease, is characterized by abnormalities in cardiac wall thickness and chamber size, leading to impaired contraction, relaxation, conduction, rhythm, and reduced pumping ability. Aim This review aims to provide a comprehensive understanding of cardiomyopathy by examining its various aspects Method A literature survey was conducted using online databases such as PubMed, Google Scholar, and Web of Science, covering publications from January 1995 to July 2023. Result Genetic mutations in key muscle contraction genes (MYH7, MYL2, MYL3, MYBPC3, TNNT2, TPM1, TNNI3, ACTC) contribute to cardiomyopathy. Additionally, epigenetic markers in genes like FKBP5, TBX5, HAND1, POLA2, PLAAT3, and CCDC88B, along with environmental factors such as alcohol addiction, smoking, and stress, significantly influence disease risk. Genetic testing, including whole exome/genome sequencing, has revolutionized diagnosis, enabling early detection and intervention. Familial genetic testing facilitates personalized management. Conclusion Cardiomyopathy is a complex disease with genetic and environmental influences. Various techniques, including genetic testing, aid in its identification and management. Furthermore, machine learning (ML) techniques have emerged as valuable tools in understanding and predicting cardiomyopathy outcomes.

Ischemic stroke susceptibility associated with ALPK1 single nucleotide polymorphisms by inhibiting URAT1 in uric acid hemostasis

ObjectivesIschemic stroke (IS) prevalence rising annually, the necessity of discovering non-interventional genetic influences is progressing. Single nucleotide polymorphism (SNP) plays a pivotal role in stable inheritance of disease susceptibility. Based on the relationship between Alpha- Kinase 1 (ALPK1) and traditional IS risk factors especially hyperuricemia, our study investigated the association and function of ALPK1 SNPs with IS susceptibility. MethodsA case-control study of 1539 patients and 933 controls from northeast China was conducted. Genotyping information of ALPK1 rs2074379 and rs2074388 was collected. Four types of plasmids including rs2074379/rs2074388 G/G, A/G, G/A, and A/A were transfected into 293T cells to observe ALPK1 and SLC22A12 expression. Possible ALPK1 structures of different SNPs were predicted online. ResultsGenotype GG (OR = 1.371, CI = 1.029–1.828, P = 0.031) and GA (OR = 1.326, CI = 1.110–1.584, P = 0.002) of rs2074379 and GA of rs2074388 (OR = 1.359, CI = 1.137–1.624, P = 0.001) were found significantly susceptible to IS, with G allele on sites to be a risk allele. Rs2074379 had a multiplicative interaction with hyperuricemia (OR = 1.637, CI = 1.157–2.315, P = 0.005). Uric acid levels differed in genotypes (P < 0.001). The expression of ALPK1 (P < 0.01) and SLC22A12 in membrane urate transporter 1 (URAT1) protein (P < 0.05) functionally changed with G allele on either site. With glycine changing into aspartic acid at rs2074388, the protein secondary structure changed, but the ALPK1 protein subtype remained still. ConclusionsALPK1 rs2074379 and rs2074388 SNPs were functionally associated with IS susceptibility. The wild allele progressed IS risk probably by reducing ALPK1 expression and inhibiting URAT1 raising the uric acid level, contributing to further exploration of pathogenetic mechanisms of stroke.Chinese Clinical Trial Registration number: ChiCTR-COC-17013559.

Functional excitation-inhibition ratio indicates near-critical oscillations across frequencies

Abstract The concept of excitation/inhibition (E/I) balance plays an important role in understanding brain function in health and disease. We recently introduced an algorithm to determine a functional E/I ratio based on the critical brain dynamics that emerge in neuronal networks balancing between order and disorder. Little, however, is known about the frequency specificity of E/I regulation and how to measure it. Here, we optimized the algorithm for measuring functional excitation-inhibition ratio (fE/I) in narrow frequency ranges and validated it on a computational model of critical oscillations and EEG data. In the computational model, we confirmed that fE/I discriminated E/I connectivity differences across a wide range of frequencies (1–150 Hz). Twin EEG data revealed significant genetic influences on fE/I across frequencies, whereas contrasting eyes-open and -closed EEG indicated functional changes of fE/I restricted to a subset of alpha and beta oscillations and brain regions. We propose that assessing fE/I with finer frequency resolution will prove useful for understanding the functional role of E/I regulation in a spectrally refined fashion in health and disease.

Genetics, age, and diet influence gut bacterial communities and performance of black soldier fly larvae (Hermetia illucens)

BackgroundThe gut microbiota of black soldier fly larvae (BSFL, Hermetia illucens) play a crucial role in recycling various organic waste streams. This capability is linked to the presence of a potential common core microbiota in BSFL. However, subjective thresholds for defining core taxa and the difficulty of separating genetic and environmental influences have prevented a clear consensus in the literature. We analysed the gut bacterial communities of two genetically distinct BSF lines (wild type (WT) and lab-adapted line (LD)) raised on ten different diets based on common agricultural by-products and food waste in Southeast Asia.ResultsHigh-throughput 16S rRNA gene sequencing revealed that gut bacterial communities were significantly influenced by genetics (p = 0.001), diet (plant/meat-dominated; p = 0.001), larval age (p = 0.001), and the interactions between all three (p = 0.002). This led us to investigate both common core taxa and lineage-specific core taxa. At a strict > 97% prevalence threshold, four core taxa were identified: Providencia_A_732258, an unclassified genus within the family Enterococcaceae, Morganella, and Enterococcus_H_360604. A relaxed threshold (> 80% prevalence) extended the core to include other potential common core taxa such as Klebsiella, Proteus, and Scrofimicrobium. Our data suggest that Proteus, Scrofimicrobium, Corynebacterium, Vagococcus_B, Lysinibacillus_304693 (all LD), and Paenibacillus_J_366884 (WT) are lineage-specific rather than members of a common core (> 90% prevalence in either LD or WT, with prevalence significantly different between lines (p ≤ 0.05)). Positive correlations were observed between several core genera and larval performance in LD, typical of a highly optimized lab-adapted line. Interestingly, only members of the genus Providencia appeared to play a crucial role in most aspects of larval performance in both genetic lineages.ConclusionOur study demonstrates that the gut microbiota of BSFL is influenced by genetic factors, diet composition, larval age, and their interactions. We identified a distinct lineage-specific core microbiota, emphasizing genetic background’s role. Future studies should apply a standardized high prevalence threshold of at least > 90% unless there is a valid reason for relaxation or sample exclusion. The consistent association of Providencia spp. with larval performance across both genetic lines highlights their crucial role in the BSFL gut ecosystem.

Under the name of “Lua”: revisiting genetic heterogeneity and population ancestry of Austroasiatic speakers in northern Thailand through genomic analysis

BackgroundAustroasiatic (AA)-speaking populations in northern Thailand are of significant interest due to their status as indigenous descendants and their location at the crossroads of AA prehistoric distribution across Southern China, the Indian Subcontinent, and Mainland Southeast Asia. However, the complexity of ethnic identification can result in inaccuracies regarding the origin and migration history of these populations. To address this, we have conducted a genome-wide SNP analysis of 89 individuals from two Lavue and three Lwa-endonym populations. We then combined our outcomes with previously published data to elucidate the genetic diversity and clustering of AA groups in northern Thailand.ResultsOur findings align with existing linguistic classifications, revealing different genetic compositions among the three branches of the Mon-Khmer subfamily within the AA family: Monic, Khmuic, and Palaungic. Although the term “Lua” ethnicity is confusingly used to identify ethnic groups belonging to both Khmuic and Palaungic branches, our genomic data indicate that the Khmuic-speaking Lua living on the eastern side of the region are relatively distant from the Palaungic-speaking Lavue and Lwa populations living on the western side. The Lavue populations, primarily inhabiting mountainous areas, exhibit a genetic makeup unique to the AA family, with a close genetic relationship to the Karenic subgroup of the Sino-Tibetan language family. Conversely, the Lwa and Blang populations, residing in lowland river valleys, display genetic signatures resulting from admixture with Tai-Kadai-speaking ethnic groups.ConclusionUtilizing genome-wide SNP markers, our findings indicate genetic heterogeneity among the Lua, Lavue, and Lwa ethnic groups. The intricate interplay of genetics, cultural heritage, and historical influences has shaped these ethnic communities. Our study underscores the importance of accurate ethnic classifications, emphasizing the use of self-identified endonyms, names created and used by the ethnic groups themselves. This approach respects the AA communities in northern Thailand and acknowledges their significant contributions to advancing our understanding of genetic anthropology.

Exploring Transgressive Segregation for Enhanced Yield in F2 Segregants of Sesame (Sesamum indicum L.)

The experiment involved F2 generation of three superior crosses of sesame: Thilak X Ayali 1, Thilathara X Ayali 2 and Thilak X Ayali 5, grown in a Compact Family Block Design. A total of 200 plants were grown with a spacing of 30 x 25 cm, and observations were recorded on yield related characters. Significant variation was found among most traits, except for capsule length, capsule width, number of seeds per capsule and the number of primary branches. The cross Thilathara X Ayali 2 exhibited a high frequency of transgressive segregants for multiple traits, particularly for seed yield per plant, making it highly promising for further breeding efforts. Plant height had the highest mean and range, showing considerable potential for selection. CV analysis revealed high variability for traits like the number of capsules per plant and seed yield per plant. In contrast, low variability and high stability was observed for traits like capsule length, number of seeds per capsule and days to maturity. Higher PCV and GCV were recorded for traits like days to first flowering, number of capsules per plant, and seed yield per plant, showing substantial genetic and environmental influences. Moderate PCV and GCV were found for plant height and days to maturity, while traits like capsule length, number of seeds per capsule, and capsule width had the lowest PCV and GCV, indicating limited genetic variation. Days to first flowering and days to maturity showed high heritability combined with high genetic advance, suggesting the preponderance of additive gene action and are ideal for simple selection. Traits like capsule length, capsule width, and number of seeds per capsule showed low heritability and genetic advance, making them less ideal for selection. The cross, Thilathara X Ayali 2 should be prioritized in future generations to recover desirable segregants, especially for economically important traits like seed yield.

EMPOWERMENT THROUGH UNDERSTANDING: A DEEP DIVE INTO LEARNING DIFFICULTIES

&lt;p&gt;This qualitative study focuses on a detailed investigation into the complexities of learning difficulties, aiming to uncover the underlying causes, identify prevalent symptoms, discern societal attitudes, and evaluate the efficacy of various intervention strategies. By engaging a substantial participant base of 863 individuals, the study leverages qualitative methodologies to shed light on the nuanced experiences of those with learning disabilities, including challenges related to perception, skill acquisition, and social integration. The research outcomes emphasize the critical need for a holistic understanding of learning difficulties, taking into account the intricate interplay between psychological, genetic, environmental, and educational influences. Such comprehensive insights are pivotal for the development of tailored support and intervention programs, with the potential to significantly impact educational policies and practices. This study not only enriches the academic and clinical discourse surrounding learning disabilities but also advocates for enhanced societal support mechanisms, thereby aiming to improve the educational journey and quality of life for individuals facing these challenges.&lt;/p&gt;&lt;p&gt; &lt;/p&gt;&lt;p&gt;&lt;strong&gt; Article visualizations:&lt;/strong&gt;&lt;/p&gt;&lt;p&gt;&lt;img src="/-counters-/soc/0746/a.php" alt="Hit counter" /&gt;&lt;/p&gt;

Analysis of ABCB1 Gene Polymorphisms and Their Impact on Tacrolimus Blood Levels in Kidney Transplant Recipients.

Tacrolimus (Tc) is an immunosuppressant used in transplant patients, but its therapeutic range is narrow, making precise dosing essential. This study investigates the association of three single nucleotide polymorphisms (SNPs) (ABCB1 3435C>T, 1236C>T, 2677G>T/A) with Tc levels over time to gain better insights into their role in personalized medicine. We conducted the study over four distinct periods: 1-14 days, 15-30 days, 31-60 days, and beyond 60 days post-transplantation. The analysis included allele, genotype, haplotype, and diplotype frequencies of the three SNPs concerning Tc blood levels. Statistical significance was determined, and false discovery rate (PFDR) correction was applied where appropriate. Significant associations were found between the C (ABCB1 C1236T), A alleles (ABCB1 G2677T/A), the CAC haplotype and lower Tc levels. The CAC-TGT and TGT-TGT diplotypes significantly influence how patients metabolize the drug. The TGT haplotype and the AA genotype (ABCB1 G2677T/A) were associated with higher Tc levels, suggesting a long-term genetic influence. Genetic factors, specifically certain SNPs and diplotypes, significantly impact Tc blood levels, with their influence varying over time.

Genetic influences, lifestyle and psychosocial aspects in relation to metabolically healthy obesity and conversion to a metabolically unhealthy state.

About 10%-30% of individuals with obesity are metabolically healthy, but the specific characteristics of the metabolically healthy obesity (MHO) phenotype remain unclear. We aimed to examine how physical activity, education, depressive symptoms and genetic predisposition to obesity differ between individuals with MHO and those with metabolically unhealthy obesity (MUO), and whether these factors predict stability in MHO or conversion to a metabolically unhealthy state. We retrieved data on 9809 individuals with obesity from the Health and Retirement Study collected between 2006 and 2016. We compared how physical activity, education, depressive symptoms and a polygenic score for higher body mass index (BMI) (PGSBMI) differed cross-sectionally between MHO and MUO using logistic regression. We then examined if the same factors predict conversion to a metabolically unhealthy state over 4 years in individuals with MHO. Individuals with MHO had higher physical activity (odds ratio [OR] = 0.81), higher education (OR = 0.83) and lower depressive symptoms (OR = 1.14) compared to those with MUO but did not differ in the PGSBMI. The associations were slightly attenuated in mutually adjusted models. None of the factors were associated with conversion from MHO to a metabolically unhealthy state. However, a higher PGSBMI indicated 24% lower risk of conversion to a metabolically unhealthy state (p = 0.07). Physical activity, education and depressive symptoms differed between MHO and MUO, even when mutually adjusted for, but did not predict conversion from a metabolically healthy to unhealthy state. Although not statistically significant, the results indicated that those with genetically predicted high BMI are more likely to maintain MHO and not convert to a metabolically unhealthy state.

Genome-wide association study of subfoveal choroidal thickness in a longitudinal cohort of older adults

To identify genetic influences on subfoveal choroidal thickness of older adults using a genome-wide association study (GWAS). We recruited 300 participants from the population-based Korean Longitudinal Study on Health and Aging (KLoSHA) and Korean Longitudinal Study on Cognitive Aging and Dementia (KLOSCAD) cohort studies and 500 participants from the Bundang age-related macular degeneration (AMD) cohort study dataset. We conducted a GWAS on older adult populations in the KLoSHA and KLOSCAD cohorts. Single nucleotide polymorphisms (SNPs) associated with choroidal thickness were identified with P values < 1.0 × 10−4 in both the right and left eyes, followed by validation using the Bundang AMD cohort dataset. This association was further confirmed by a functional in vitro study using human umbilical vein endothelial cells (HUVECs). The ages of the cohort participants in the discovery and validation datasets were 73.5 ± 3.3 and 71.3 ± 7.9 years, respectively. In the discovery dataset, three SNPs (rs1916762, rs7587019, and rs13320098) were significantly associated with choroidal thickness in both eyes. This association was confirmed for rs1916762 (genotypes GG, GA, and AA) and rs7587019 (genotypes GG, GA, and AA), but not for rs13320098. The mean choroidal thickness decreased by 56.7 μm (AA, 73.8%) and 31.1 μm (GA, 85.6%) compared with that of the GG genotype of rs1916762, and by 55.4 μm (AA, 74.2%) and 28.2 μm (GA, 86.7%) compared with that of the GG genotype of rs7587019. The SNPs rs1916762 and rs7587019 were located close to the FAM124B gene near its cis-regulatory region. Moreover, FAM124B was highly expressed in vascular endothelial cells. In vitro HUVEC experiments showed that the inhibition of FAM124B was associated with decreased vascular endothelial proliferation, suggesting a potential mechanism of choroidal thinning. FAM124B was identified as a susceptibility gene affecting subfoveal choroidal thickness in older adults. This gene may be involved in mechanisms underlying retinal diseases associated with altered choroidal thickness, such as age-related macular degeneration.

Exaggerated Blood Pressure Response to Exercise Is a Risk of Future Hypertension Even in Healthy, Normotensive Young Individuals—Potential Preventive Strategies for This Phenomenon?

Physical activity and regular exercise are well known to reduce the risks of cerebrovascular and cardiovascular diseases, leading the American College of Sports Medicine to endorse the concept that “exercise is medicine”. However, a single bout of exercise temporarily raises arterial blood pressure (BP) to meet the metabolic demands of working muscle, and this BP response is particularly exaggerated in older adults and patients with cardiovascular conditions, such as hypertension, resulting in an exaggerated BP response during exercise. This presents a paradox: while regular exercise is crucial for preventing these diseases, excessively high BP responses during exercise could increase the risk of vascular damage. The mechanisms underlying this exaggerated BP response during exercise remain unclear, and effective exercise regimens for these populations have yet to be established. Currently, low-intensity exercise is recommended; however, its efficacy in disease prevention is uncertain. Notably, even among healthy individuals, there is significant variation in the BP response to exercise. Some healthy individuals, despite having normal resting BP, exhibit an exaggerated BP response during physical activity. Importantly, these individuals are often unaware that their BP becomes excessively elevated during physical activity. Repeated exposure to these heightened BP responses through regular physical activity may increase their long-term risk of cardiovascular disease. How can we prevent disease development in these individuals while still ensuring the effectiveness of exercise? Some studies have shown that individuals with a family history of hypertension may experience this phenomenon even in children and adolescents. Additionally, left ventricular hypertrophy contributes to an exaggerated BP response to exercise, suggesting a possible genetic influence. Conversely, other reports indicate that factors such as arterial stiffness, obesity, and low exercise capacity also contribute to this exaggerated response. Our recent preliminary data suggest that the cognitive benefits of exercise may be diminished in individuals who exhibit an exaggerated BP response during exercise. This implies that individuals with an exaggerated BP response, despite having normal resting BP, may not fully benefit from exercise. In this perspective paper, we review the physiological aspects of this phenomenon and explore strategies to address it. Additionally, we discuss BP responses in athletes within this content. Our goal is to prevent disease while maximizing the benefits of exercise for healthy individuals with an exaggerated BP response, as well as for elderly and cardiovascular patients.

Biomarkers of cognitive and memory decline in psychotropic drug users.

Psychotropic drugs are vital in psychiatry, aiding in the management of mental health disorders. Their use requires an understanding of their pharmacological properties, therapeutic applications, and potential side effects. Ongoing research aims to improve their efficacy and safety. Biomarkers play a crucial role in understanding and predicting memory decline in psychotropic drug users. A comprehensive understanding of biomarkers, including neuroimaging, biochemical, genetic, and cognitive assessments, is essential for developing targeted interventions and preventive strategies. In this narrative review, we performed a comprehensive search on PubMed and Google using review-specific terms. Clinicians should use a multifaceted approach, including neurotransmitter analysis, neurotrophic factors, miRNA profiling, and cognitive tasks for early intervention and personalized treatment. Anxiolytics' mechanisms involve various neurotransmitter systems and emerging targets. Research on biomarkers for memory decline in anxiolytic users can lead to early detection and intervention, enhancing clinical practices and aligning with precision medicine. Mood stabilizer users can benefit from early detection of memory decline through RNA, neurophysiological, and inflammatory biomarkers, promoting timely interventions. Performance-enhancing drugs may boost athletic performance in the short term, but their long-term health risks and ethical issues make their use problematic. Long-term use of psychotropic performance enhancers in athletes shows changes in biomarkers of cognitive decline, necessitating ongoing monitoring and intervention strategies. Understanding these genetic influences on memory decline helps pave the way for personalized approaches to prevent or mitigate cognitive deterioration, emphasizing the importance of genetic screening and early interventions based on an individual's genetic profile. Future research should focus on refining these biomarkers and protective measures against cognitive deterioration. Overall, a comprehensive understanding of biomarkers in psychotropic drug users is essential for developing targeted interventions and preventive strategies.

Association of Resilience-Related Life Experiences on Variability on Age of Onset in Dominantly Inherited Alzheimer Disease.

It remains unknown whether the associations between protective lifestyles and sporadic dementia risk reported in observational studies also affect age at symptom onset (AAO) in autosomal dominant Alzheimer disease (ADAD) with predominant genetic influences. We investigated the associations between resilience-related life experiences and interindividual AAO variability in ADAD. We performed a longitudinal and confirmatory analysis of the Dominantly Inherited Alzheimer Network prospective observational cohort (January 2009-June 2018, follow-up duration 2.13 ± 2.22 years), involving clinical, CSF, and lifestyle/behavioral assessments. We performed a 2-pronged comprehensive resilience assessment in each cohort. Cohort 1, incorporating the general resilience definition (cognitive maintenance [Clinical Dementia Rating = 0] despite high pathology), included carriers during the periods of significant CSFp-tau181 variability and grouped into resilience/resistance outcome bins according to the dichotomous pathologic and cognitive statuses, subcategorized by the estimated years from expected symptom onset (EYO). Cohort 2, focused on ADAD-specific genetically determined time frame characterizing the onset predictability, included asymptomatic participants with available preclinical lifestyle data and AAO outcomes and grouped into delayed or earlier AAO relative to the parental AAO. Associations of cognitive, CSFp-tau181, and lifestyle/behavioral predictors with binary outcomes were investigated using logistic regression. Of 320 carriers (age 38.19 ± 10.94 years, female 56.25%), cohort 1 included 218 participants (39.00 ± 9.37 years, 57.34%) and cohort 2 included 28 participants (43.34 ± 7.40 years, 71.43%). In cohort 1, 218 carriers after -20 EYO, when the interindividual variability (SD) of CSFp-tau181 first became more than twice greater in carriers than in noncarriers, were grouped into low-risk control (asymptomatic, low pathology, n = 103), high-resilience (asymptomatic despite high pathology, n = 60), low-resilience (symptomatic despite low pathology, n = 15), and susceptible control (symptomatic, high pathology, n = 40) groups. Multivariable predictors of high resilience, controlling for age and depression, included higher conscientiousness (odds ratio 1.051 [95% CI 1.016-1.086], p = 0.004), openness to experience (1.068 [1.005-1.135], p = 0.03) (vs. susceptible controls), and agreeableness (1.082 [1.015-1.153], p = 0.02) (vs. low resilience). From 1 to 3 years before parental AAO (cohort 2), the multivariable predictor of delayed AAO, controlling for CSFp-tau181, was higher conscientiousness (0.916 [0.845-0.994], p = 0.036). Among the cognitively and socially integrated life experiences associated with resilience, measures of conscientiousness were useful indicators for evaluating resilience and predicting future dementia onset in late preclinical ADAD.