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Metabolic diseases result from interactions between genetic and lifestyle factors. Understanding the combined influences of single-nucleotide polymorphisms (SNPs) and lifestyle is crucial. This study employs genetic risk scores (GRS) to assess SNPs, providing insight beyond single gene/SNP studies by revealing synergistic effects. Here, we aim to investigate the association of a 23-SNP GRS with metabolic disease-related traits (obesity and type 2 diabetes) to understand if these associations are altered by lifestyle/dietary factors. For this study, 106 Minangkabau women were included and underwent physical, anthropometric, biochemical, dietary and genetic evaluations. The interaction of GRS with lifestyle factors was analyzed using linear regression models, adjusting for potential confounders. No statistically significant associations were observed between GRS and metabolic traits; however, this study demonstrates a novel interaction observed between 13-SNP GRS and monounsaturated fatty acid (MUFA) intake, and that it had an effect on HbA1c levels (p = 0.026). Minangkabau women with low MUFA intake (≤7.0 g/day) and >13 risk alleles had significantly higher HbA1c levels (p = 0.010). This finding has implications for public health, suggesting the need for large-scale studies to confirm our results before implementing dietary interventions in the Indonesian population. Identifying genetic influences on dietary response can inform personalized nutrition strategies to reduce the risk of metabolic disease.

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BACKGROUND: Inflammatory bowel disease (IBD) and systemic lupus erythematosus (SLE) are autoimmune diseases that often coexist clinically. This phenomenon might be due to shared genetic components. METHODS: Genome-wide association study (GWAS) data for IBD and SLE were analyzed to determine both global and local genetic correlations using three methodologies: linkage disequilibrium score regression (LDSC), genetic covariance analyzer (GNOVA), and SUPERGNOVA. The genetic overlap and risk loci were subsequently examined using the conditional/conjunctional false discovery rate (cond/conjFDR) statistical framework. Furthermore, a multi-trait analysis of MTAG was employed to validate the loci, followed by an LDSC analysis focusing on tissue-specific gene expression. RESULTS: GWAS findings demonstrated a marked global genetic correlation between IBD (including Crohn's disease and ulcerative colitis) and SLE. Locally, SLE showed a strong association with IBD and Crohn's disease on chromosomes 10, 19, and 22. ConjFDR analysis confirmed the genetic overlap and identified relevant genetic risk loci. MTAG further validated several shared susceptibility genes. Additionally, the LDSC-SEG analysis results indicate that IBD (including CD and UC) and SLE are jointly enriched in the tissues of Spleen and Whole Blood. CONCLUSION: This study confirms a genetic overlap between IBD and SLE, identifying marked comorbid genes and offering new insights for treating these diseases.

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This study aimed to investigate the associations between carbohydrate intake and gout risk, along with interactions between genetic susceptibility and carbohydrates, and the mediating roles of biomarkers. We included 187,387 participants who were free of gout at baseline and completed at least one dietary assessment in the UK Biobank. Cox proportional hazard models were used to estimate the associations between carbohydrate intake and gout risk. Over a median follow-up of 11.69 years, 2548 incident cases of gout were recorded. Total carbohydrate intake was associated with a reduced gout risk (Q4 vs. Q1: HR 0.67, 95% CI 0.60-0.74), as were total sugars (0.89, 0.80-0.99), non-free sugars (0.70, 0.63-0.78), total starch (0.70, 0.63-0.78), refined grain starch (0.85, 0.76-0.95), wholegrain starch (0.73, 0.65-0.82), and fiber (0.72, 0.64-0.80), whereas free sugars (1.15, 1.04-1.28) were associated with an increased risk. Significant additive interactions were found between total carbohydrates and genetic risk, as well as between total starch and genetic risk. Serum urate was identified as a significant mediator in all associations between carbohydrate intake (total, different types, and sources) and gout risk. In conclusion, total carbohydrate and different types and sources of carbohydrate (excluding free sugars) intake were associated with a reduced risk of gout.

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BACKGROUND: Blood lipid levels were associated with chronic kidney disease (CKD) in patients with type 2 diabetes (T2D), but the genetic basis and causal nature remains unclear. OBJECTIVE: This study aimed to investigate the relationships of lipids and their fractions with CKD in patients with T2D. METHODS: Our prospective analysis involved 8,607 White participants with T2D but no CKD at baseline from the UK Biobank. Five common lipid traits were included as exposures. Weighted genetic risk scores (GRSs) for these lipid traits were developed. The causal associations between lipid traits, as well as lipid fractions, and CKD were explored using linear or nonlinear Mendelian randomization (MR). The 10-year predicted probabilities of CKD were evaluated via integrating MR and Cox models. RESUTLS: Higher GRS of apolipoprotein B (ApoB) was associated with an increased CKD risk (HR[95 % CI]:1.07[1.02,1.13] per SD;P = 0.008) after adjusting for potential confounders. Linear MR indicated a positive association between genetically predicted ApoB levels and CKD (HR[95 % CI]:1.53[1.12,2.09];P = 0.008), but no evidence of associations was found between other lipid traits and CKD in T2D. Regarding 12 ApoB-contained lipid fractions, a significant causal association was found between medium very-low-density lipoprotein particles and CKD (HR[95 % CI]:1.16[1.02,1.32];P = 0.020). Nonlinear MR did not support nonlinearity in these causal associations. The 10-year probability curve showed that ApoB levels was positively associated with the risk of CKD in patients with T2D. CONCLUSION: Lower ApoB levels were causally associated with a reduced risk of CKD in patients with T2D, positioning ApoB as a potential therapeutic target for CKD prevention in this population.

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Given the high growth rates of cognitive decline among the elderly population and the lack of effective etiological treatments, early diagnosis of cognitive impairment progression is an imperative task for modern science and medicine. It is of particular interest to identify predictors of an unfavorable subsequent course of cognitive disorders, specifically, rapid progression. Our study assessed the informative role of various risk factors on the dynamics of cognitive impairment among mild cognitive impairment (MCI) patients. The study included patients with MCI (N = 338) who underwent neuropsychological assessment, magnetic resonance imaging (MRI) examination, blood sampling for general and biochemical analysis, APOE genotyping, and polygenic risk score (PRS) evaluation. The APOE ε4/ε4 genotype was found to be associated with a diminished overall cognitive scores initial assessment and negative cognitive dynamics. No associations were found between cognitive changes and the PRS. The progression of cognitive impairment was associated with the width of the third ventricle and hematological parameters, specifically, hematocrit and erythrocyte levels. The absence of significant associations between the dynamics of cognitive decline and PRS over three years can be attributed to the provided suitable medical care for the prevention of cognitive impairment. Adding other risk factors and their inclusion in panels assessing the risk of progression of cognitive impairment should be considered.

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Background: Large population-based DNA biobanks linked to electronic health records (EHRs) may provide advantages over traditional study designs for identifying genetic drivers of ARDS. Research Question: Can ARDS be identified in an EHR biobank, and can this approach validate a previously reported genetic risk factor for ARDS? Study Design and Methods: We analyzed two genotyped cohorts from one academic medical center: a prospective biomarker study of critically ill adults (VALID cohort), and hospitalized participants in a de-identified EHR biobank (BioVU). ARDS status was assessed by clinician-investigator review in VALID and an EHR-derived algorithm in BioVU (EHR-ARDS). We tested the association between the MUC5B promoter polymorphism (rs35705950) with development of ARDS/EHR-ARDS in each cohort. Results: In VALID, 2,795 patients were included, age was 55 [43, 66] (median [IQR]) years, and 718 (25.7%) developed ARDS. In BioVU, 9,025 hospitalized participants were included, age was 60 [48, 70] , and 1,056 (11.7%) developed EHR-ARDS. We observed a significant interaction between age and rs35705950 on ARDS risk in VALID: in older patients rs35705950 was associated with increased ARDS risk (OR: 1.44; 95%CI 1.08-1.92; p=0.012) whereas among younger patients this effect was attenuated (OR: 0.84; 95%CI: 0.62-1.14; p=0.26). In BioVU, rs35705950 was associated with increased risk for EHR-ARDS among all participants (OR: 1.20; 95%CI: 1.00-1.43, p=0.043) and this relationship did not vary by age. The polymorphism was also associated with more severe oxygenation impairment among BioVU participants who required mechanical ventilation. Interpretation: The MUC5B promoter polymorphism was associated with ARDS in two cohorts of at-risk hospitalized adults. Although age-related effect modification was observed only in the prospective biomarker cohort, the EHR cohort identified a consistent association between MUC5B and ARDS risk regardless of age and a novel association with oxygenation impairment. Our study highlights the potential for EHR biobanks to enable precision-medicine ARDS studies.

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BACKGROUND: Few studies have explored the association between stair climbing and osteoarthritis (OA) to determine whether the former is a protective or risk factor for the latter. This study prospectively evaluated the associations among stair climbing, genetic susceptibility, and their interaction with the risk of incident hip/knee OA. METHODS: The cohort analyses included 398,939 participants from the UK Biobank. Stair climbing was assessed using a questionnaire. Genetic risk scores (GRSs) consisting of 70, 83, and 87 single-nucleotide polymorphisms for hip, knee, and hip/knee OA were constructed. Cox proportional hazard regression models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for the associations among stair climbing, genetic predisposition, and hip and/or knee OA risk. RESULTS: After 3,621,735 person-years of follow-up, 31,940 patients developed OA. Stair climbing was positively associated with incident hip/knee (P for trend<0.001) and knee (P for trend<0.0001) OA but not hip OA. After adjustments, compared with no stair climbing, climbing >150 steps/day was associated with a higher risk of hip/knee OA (HR, 1.08; 95% CI, 1.03-1.12) and knee OA (HR, 1.13; 95% CI, 1.06-1.20). Although no significant interaction between stair climbing and the GRS of OA risk was found, the above associations were only significant in participants with middle and high GRSs. CONCLUSION: A higher frequency of stair climbing was positively associated with the risk of knee OA but not hip OA, highlighting the importance of avoiding frequent stair climbing in preventing knee OA, especially in genetically predisposed individuals.

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The omnigenic model posits that genetic risk for traits with complex heritability involves cumulative effects of peripheral genes on mechanistic "core genes," suggesting that in a network of genes, those closer to clusters including core genes should have higher GWAS signals. In gene co-expression networks, we confirmed that GWAS signals accumulate in genes more connected to risk-enriched gene clusters, highlighting across-network risk convergence. This was strongest in adult psychiatric disorders, especially schizophrenia (SCZ), spanning 70% of network genes, suggestive of super-polygenic architecture. In snRNA-seq cell type networks, SCZ risk convergence was strongest in L2/L3 excitatory neurons. We prioritized genes most connected to SCZ-GWAS genes, which showed robust association to a CRISPRa measure of PGC3 regulation and were consistently identified across several brain regions. Several genes, including dopamine-associated ones, were prioritized specifically in the striatum. This strategy thus retrieves current drug targets and can be used to prioritize other potential drug targets.

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OBJECTIVES: This study aimed to investigate the interplay between genetic susceptibility and socioeconomic disparities on psychiatric disorders. METHODS: In this study, we utilized data from the UK Biobank to analyze the Generalized Anxiety Disorder (GAD)-7 scale (N = 74,425) and the Patient Health Questionnaire (PHQ)-9 (N = 74,101), along with the Index of Multiple Deprivation (IMD). The polygenic risk score (PRS) was calculated to assess the genetic risk associated with GAD-7/PHQ-9 scores, and the individuals were classified into low, medium, and high genetic risk groups according to tertiles of PRSs related to the GAD-7/PHQ-9. Linear regression models were used to explore the relationships between GAD-7/PHQ-9 scores and IMD scores in patients with different genetic susceptibilities. RESULTS: Disadvantaged socioeconomic status was associated with the risk of anxiety and depression across all strata of genetic risk, and stronger associations were shown for individuals with greater genetic susceptibility. From low to high genetic risk, the risk of psychiatric disorders increased for the GAD-7 (ß = 0.002 to 0.032) and PHQ-9 (ß = 0.003 to 0.045) scores. In addition, strong associations of high genetic risk with anxiety (ß = 0.875) and depression (ß = 1.152) were detected in the IMD quartile 4 group compared with the least deprivation quartile group. Furthermore, income and employment were estimated to contribute strongly to anxiety (ßemployment = 7.331, ßincome = 4.492) and depression (ßemployment = 9.951, ßincome = 6.453) in the high genetic risk group. CONCLUSION: The results suggest that we should pay more attention to psychiatric disorders with high genetic susceptibility and try to improve their socioeconomic status to prevent the development of psychiatric disorders.

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BACKGROUND: Both body mass index (BMI) and genetic factors independently contribute to cardiovascular disease (CVD). However, it is unclear whether genetic risk modifies the association between BMI and the risk of incident CVD. This study aimed to investigate whether BMI categories and genetic risk jointly and interactively contribute to incident CVD events, including hypertension (HTN), atrial fibrillation (AF), coronary heart disease (CHD), stroke, and heart failure (HF). METHODS: A total of 496,851 participants from the UK Biobank with one or more new-onset CVD events were included in the analyses. BMI was categorized as normal weight (< 25.0 kg/m2), overweight (25.0-29.9 kg/m2), and obesity (≥ 30.0 kg/m2). Genetic risk for each outcome was defined as low (lowest tertile), intermediate (second tertile), and high (highest tertile) using polygenic risk score. The joint associations of BMI categories and genetic risk with incident CVD were investigated using Cox proportional hazard models. Additionally, additive interactions were evaluated. RESULTS: Among the 496,851 participants, 270,726 (54.5%) were female, with a mean (SD) age was 56.5 (8.1) years. Over a median follow-up (IQR) of 12.4 (11.5-13.1) years, 102,131 (22.9%) participants developed HTN, 26,301 (5.4%) developed AF, 32,222 (6.9%) developed CHD, 10,684 (2.2%) developed stroke, and 13,304 (2.7%) developed HF. Compared with the normal weight with low genetic risk, the obesity with high genetic risk had the highest risk of CVD: HTN (HR: 3.96; 95%CI: 3.84-4.09), AF (HR: 3.60; 95%CI: 3.38-3.83), CHD (HR: 2.76; 95%CI: 2.61-2.91), stroke (HR: 1.44; 95%CI: 1.31-1.57), and HF (HR: 2.47; 95%CI: 2.27-2.69). There were significant additive interactions between BMI categories and genetic risk for HTN, AF, and CHD, with relative excess risk of 0.53 (95%CI: 0.43-0.62), 0.67 (95%CI: 0.51-0.83), and 0.37 (95%CI: 0.25-0.49), respectively. CONCLUSIONS: BMI and genetic factors jointly and interactively contribute to incident CVD, especially among participants with high genetic risk. These findings have public health implications for identifying populations more likely to have cardiovascular benefit from weight loss interventions.

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BACKGROUND: Latines suffer from breast cancer (BC), due to elevated biological and social determinants of health (SDOH) risks. This study compares the effects of different strategies on uptake of cancer genetic services, specifically hereditary cancer risk assessment, genetic counseling, and genetic testing, and risk-based BC care. DESIGN/METHODS: In Chicago, Illinois, Aim 1 participants are recruited from a federally qualified health center (FQHC) and community venues. For Aim 1, eligible participants: (1) are female; (2) are Latine; (3) are 30+ years old; (4) have personal or family history of BC or cancers with shared hereditary mutations; (5) have at least one SDOH risk; and (6) have not received any cancer genetic services. Participants are randomly assigned to different study arms. Both arms include phone-based sessions, FQHC-based navigation for SDOH, and low- or no-cost cancer genetic services. The educate sessions focus on risk assessment and prevention. The empower sessions focus on risk assessment and equip participants with the skills to share information about FQHC-based cancer genetic services. For Aim 2, eligible participants are: (1) female; (2) network members of Aim 1 participants; and (3) eligible for BC screening based on guidelines recommended by the American Cancer Society (ACS). Primary outcomes include uptake of any cancer genetic services. Analyses will also explore intervention differences by neighborhood context. DISCUSSION: This is one of the first trials focused on Latines' participation in cancer genetic services and risk-based BC care within the context of SDOH - which has major implications for equity in precision cancer prevention.

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Background: There is growing interest in the intersection of frailty and heart failure (HF); however, large-sample longitudinal studies in the general population are lacking. Objectives: The goal of this study was to examine the longitudinal relationship between frailty and incident HF, and whether age and genetic predisposition could modify this association. Methods: This prospective cohort study included 340,541 participants (45.7% male; mean age 55.9 ± 8.1 years) free of HF at baseline in the UK Biobank. Frailty was assessed by using the Fried frailty phenotype and included weight loss, exhaustion, low physical activity, slow gait speed, and low grip strength. The weighted polygenetic risk score was calculated. Cox models were used to estimate these associations and the interaction between the 2 factors. Results: During a median 14.1 years of follow-up, 7,590 patients with HF were documented. Compared with nonfrail participants, both prefrail and frail participants had a positive association with the risk of incident HF (prefrail HR: 1.40 [95% CI: 1.17-1.67]; frail HR: 2.07 [95% CI: 1.67-2.57]). Exhaustion (HR: 1.21; 95% CI: 1.03-1.43), slow gait speed (HR: 1.62; 95% CI: 1.39-1.90), and low grip strength (HR: 1.31; 95% CI: 1.14-1.51) were associated with a greater risk of incident HF. Furthermore, genetic susceptibility did not significantly modify the associations (P interaction = 0.094), and the association was significantly strengthened in younger participants (P interaction = 0.008). Conclusions: Frailty status was associated with a higher risk of incident HF independent of genetic risk. A younger population may be more susceptible to HF when exposed to frailty. Whether the modification of frailty status represents another avenue for preventing HF warrants further investigation.

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Background: Cardiovascular disease (CVD), which is an important global health challenge, is expanding. One of the main factors in the occurrence of CVD is a high genetic risk. The interaction between genetic risk in CVD and nutrition is debatable. Polyphenols are one of the important dietary components that may have a protective role in people who have a high genetic risk score (GRS) for cardiometabolic risk factors. This study, conducted in overweight and obese women, examines the interaction between polyphenol intake and specific genes (MC4r, Cav-1, and Cry1) related to maintaining body balance and their interaction with cardiometabolic risk factors. Methods: This cross-sectional study included 391 women who were overweight or obese, aged 18 to 48 years, with a body mass index (BMI) between 25 and 40 kg/m2. Body composition was measured using the InBody 770 scanner. Total dietary polyphenol intake (TDPI) was assessed with a validated 147-item food frequency questionnaire (FFQ), and polyphenol intakes were determined using the Phenol-Explorer database. Serum samples underwent biochemical tests. The Genetic Risk Score (GRS) was calculated based on the risk alleles of three genes: MC4r, Cav-1, and Cry1. Results: The mean ± standard deviation (SD) age and BMI of women were 36.67 (9.1) years and 30.98 (3.9) kg/m2, respectively. The high GRS and high TDPI group had a significant negative interaction with fasting blood glucose (FBS) (p = 0.01). Individuals who had a high GRS and a high phenolic acid intake were found to have a significant negative interaction with Triglyceride (p = 0.04). Similarly, individuals with high GRS and a high intake of flavonoids had a significant negative interaction with TG (p < 0.01) and a significant positive interaction with High-density lipoprotein (HDL) (p = 0.01) in the adjusted model. Conclusion: According to our findings, those with a high GRS may have a protective effect on cardiometabolic risk factors by consuming high amounts of polyphenols. Further studies will be necessary in the future to validate this association.

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BACKGROUND: Substance use disorders (SUDs) have been consistently shown to exhibit moderate intergenerational continuity (1-3). While much research has examined genetic and social influences on addiction, less attention has been paid to clients' and lay persons' perceptions of genetic influences on the heritability of SUD (4) and implications for treatment. METHODS: For this qualitative study, twenty-six structured Working Model of the Child Interviews (WMCI) were conducted with mothers receiving inpatient SUD treatment. These interviews were thematically analyzed for themes related to maternal perceptions around intergenerational transmission of substance use behaviours. RESULTS: Findings show that over half of the mothers in this sample were preoccupied with their children's risk factors for addictions. Among this group, 29% spontaneously expressed concerns about their children's genetic risk for addiction, 54% shared worries about their children's propensity for addiction without mentioning the word gene or genetic. Additionally, 37% had challenges in even discussing their children's future when prompted. These concerns mapped onto internal working models of attachment in unexpected ways, with parents who were coded with balanced working models being more likely to discuss intergenerational risk factors and parents with disengaged working models displaying difficulties in discussing their child's future. CONCLUSION: This research suggests that the dominant discourse around the brain-disease model of addictions, in its effort to reduce stigma and self-blame, may have unintended downstream consequences for parents' mental models about their children's risks for future addiction. Parents receiving SUD treatment, and the staff who deliver it, may benefit from psychoeducation about the intergenerational transmission of SUD as part of treatment.

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Genetic variants used as instruments for exposures in Mendelian randomisation (MR) analyses may have horizontal pleiotropic effects (i.e., influence outcomes via pathways other than through the exposure), which can undermine the validity of results. We examined the extent of this using smoking behaviours as an example. We first ran a phenome-wide association study in UK Biobank, using a smoking initiation genetic instrument. From the most strongly associated phenotypes, we selected those we considered could either plausibly or not plausibly be caused by smoking. We examined associations between genetic instruments for smoking initiation, smoking heaviness and lifetime smoking and these phenotypes in UK Biobank and the Avon Longitudinal Study of Parents and Children (ALSPAC). We conducted negative control analyses among never smokers, including children. We found evidence that smoking-related genetic instruments were associated with phenotypes not plausibly caused by smoking in UK Biobank and (to a lesser extent) ALSPAC. We observed associations with phenotypes among never smokers. Our results demonstrate that smoking-related genetic risk scores are associated with unexpected phenotypes that are less plausibly downstream of smoking. This may reflect horizontal pleiotropy in these genetic risk scores, and we would encourage researchers to exercise caution this when using these and genetic risk scores for other complex behavioural exposures. We outline approaches that could be taken to consider this and overcome issues caused by potential horizontal pleiotropy, for example, in genetically informed causal inference analyses (e.g., MR) it is important to consider negative control outcomes and triangulation approaches, to avoid arriving at incorrect conclusions.

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Limited research has reported the association between MTNR1B gene polymorphisms and ischemic stroke (IS), and there is insufficient evidence on whether adopting a healthy lifestyle can mitigate genetic risks in this context. This study aimed to investigate the associations between MTNR1B gene variants (rs10830963 and rs1387153) and IS, examining the potential effect of gene-lifestyle interactions on IS risk. Conducted in northern China, this family-based cohort study involved 5116 initially IS-free subjects. Genotype data for rs10830963 and rs1387153 in MTNR1B were collected. Eight modifiable lifestyle factors, including body mass index (BMI), smoking, alcohol consumption, dietary habits, physical activity, sedentary time, sleep duration, and chronotype, were considered in calculating healthy lifestyle scores. Multilevel Cox models were used to examine the associations between MTNR1B variants and IS. Participants carrying the rs10830963-G and rs1387153-T alleles exhibited an elevated IS risk. Each additional rs10830963-G allele and rs1387153-T allele increased the IS risk by 36% (HR = 1.36, 95% CI, 1.12-1.65) and 32% (HR = 1.32, 95% CI, 1.09-1.60), respectively. Participants were stratified into low, medium, and high healthy lifestyle score groups (1537, 2188, and 1391 participants, respectively). Genetic-lifestyle interactions were observed for rs10830963 and rs1387153 (p for interaction < 0.001). Notably, as the healthy lifestyle score increased, the effect of MTNR1B gene variants on IS risk diminished (p for trend < 0.001). This study underscores the association between the MTNR1B gene and IS, emphasizing that adherence to a healthy lifestyle can mitigate the genetic predisposition to IS.

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BACKGROUND: Genetic testing serves as a valuable element of reproductive care, applicable at various stages of the reproductive journey: (i) before pregnancy, when a couple's genetic reproductive risk can be evaluated; (ii) before embryo implantation, as part of in vitro fertilization (IVF) treatment, to ascertain several inherited or de novo genetic/chromosomal diseases of the embryo before transfer; (iii) during the prenatal period, to assess the genetic costitution of the fetus. Preconception carrier screening (CS) is a genetic test typically performed on couples planning a pregnancy. The primary purpose of CS is to identify couples at-risk of conceiving a child affected by a severe genetic disorder with autosomal recessive or X-linked inheritance. Detection of high reproductive risk through CS allows prospective parents to be informed of their predisposition and improve reproductive decision-making. These include undergoing IVF with preimplantation genetic testing (PGT) or donor gametes, prenatal diagnosis, adoption, remaining childless, taking no actions. Both the presence of the affected gene (PGT-M) and chromosomal status (PGT-A) of the embryo can be comprehensively assessed through modern approaches. OBJECTIVES: We provide a review of CS and PGT applications to equip healthcare providers with up-to-date information regarding their opportunities and complexities. RESULTS AND DISCUSSION: The use of CS and PGT is currently considered the most effective intervention for avoiding both an affected pregnancy whilst using autologous gametes in couples with known increased risk, and chromosomal abnormalities. As our understanding in the genetic component in pathological conditions increases, the number of tested disorders will expand, offering a more thorough assessment of one's genetic inheritance. Nevertheless, implementation and development in this field must be accompanied by scientific and ethical considerations to ensure this approach serves the best long-term interests of individuals and society, promoting justice and autonomy and preserving parenthood and the healthcare system. CONCLUSION: The combination of CS and PGT aligns with principles of personalized medicine by offering reproductive care tailored to the individual's genetic makeup.

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