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11 pages, 932 KB  
Article
Early Insights from Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD) Patients: An Observational Study on Polygenic Risk and Liver Biomarkers
by Pietro Torre, Benedetta Maria Motta, Tommaso Sarcina, Mariano Festa, Mario Masarone and Marcello Persico
Int. J. Mol. Sci. 2025, 26(17), 8426; https://doi.org/10.3390/ijms26178426 - 29 Aug 2025
Cited by 1 | Viewed by 645
Abstract
Metabolic dysfunction-associated steatotic liver disease (MASLD) is a growing public health concern influenced by both genetic and metabolic factors. Polygenic risk scores (PRSs), which combine the effects of known single-nucleotide polymorphisms (SNPs), may improve early risk stratification. We conducted an observational study on [...] Read more.
Metabolic dysfunction-associated steatotic liver disease (MASLD) is a growing public health concern influenced by both genetic and metabolic factors. Polygenic risk scores (PRSs), which combine the effects of known single-nucleotide polymorphisms (SNPs), may improve early risk stratification. We conducted an observational study on 298 MASLD patients: 148 from a Hepatology Unit and 150 from a Bariatric Surgery Unit. Genotyping was performed for the PNPLA3, TM6SF2, MBOAT7, and GCKR variants. A PRS was calculated and used to stratify patients by genetic risk. Liver fibrosis was assessed using the FIB-4 index, and a subset also underwent transient elastography. Clinical, biochemical, and anthropometric data were analyzed across genetic strata. PRSs showed positive correlations with AST, ALT, and FIB-4, indicating increased liver injury and fibrosis risk with higher genetic burden. Transaminases increased significantly across PRS quartiles (p < 0.05), and individuals with PRS > 0.532 exhibited elevated AST, ALT, and borderline FIB-4. Variant-specific associations included PNPLA3 with increased AST and MBOAT7 with higher hepatic steatosis (CAP). Subgroup analyses revealed distinct genetic and phenotypic patterns between the two clinical cohorts. These findings support the additive role of genetic risk in MASLD progression and underscore the value of polygenic profiling for the early identification and personalized management of high-risk patients. Full article
(This article belongs to the Special Issue Role of Mutations and Polymorphisms in Various Diseases: 2nd Edition)
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14 pages, 649 KB  
Article
Polygenic Risk Score Associated with Gestational Diabetes Mellitus in an AmericanIndian Population
by Karrah Peterson, Camille E. Powe, Quan Sun, Crystal Azure, Tia Azure, Hailey Davis, Kennedy Gourneau, Shyanna LaRocque, Craig Poitra, Sabra Poitra, Shayden Standish, Tyler J. Parisien, Kelsey J. Morin and Lyle G. Best
J. Pers. Med. 2025, 15(9), 395; https://doi.org/10.3390/jpm15090395 - 22 Aug 2025
Viewed by 722
Abstract
Background/Objectives: Gestational diabetes mellitus (GDM) is a state of hyperglycemia during pregnancy, increasing the risk of birth complications, and subsequent type 2 diabetes mellitus in the mother and offspring. Risk factors such as diet, obesity, and family history have demonstrated strong association with [...] Read more.
Background/Objectives: Gestational diabetes mellitus (GDM) is a state of hyperglycemia during pregnancy, increasing the risk of birth complications, and subsequent type 2 diabetes mellitus in the mother and offspring. Risk factors such as diet, obesity, and family history have demonstrated strong association with GDM, but no clear pathophysiology has been ascertained. Methods: An analysis was conducted on 38 women with and 296 without GDM, within a case/control study of pre-eclampsia. The genetic variants examined were selected from among a published polygenic risk score of 10 variants (PRS-10). Genetic models were evaluated for each variant by multivariate logistic regression methods adjusted for age, body mass index, and pre-eclampsia. Since the genotypes for three of the PRS-10 were not available, a risk score comprising the total risk alleles among seven of the variants (PRS-7) was evaluated among those with all genotypes available. Results: Multivariate logistic regression showed significant, independent, positive associations between body mass index (BMI) and age. The posited PRS-7 showed a trend (OR 1.56, 95% CI 0.92–2.56, p = 0.070), and sensitivity analysis comprising three variants (PRS-3) was significantly associated with GDM (OR 2.43, 95% CI 1.17–5.06, p = 0.017). In univariate analysis, rs1421085 was associated with GDM (OR 0.50, 95% CI 0.26–0.95, p = 0.034), but not after adjustment for covariates, and paradoxically not for the expected risk allele. None of the other six variants showed an individual association with GDM. The previously published meta-analysis of PRS-10 showed a degree of heterogeneity (pQ= 0.03) among the three cohorts analyzed, suggesting that variant effects may differ according to the genetic background, which points to the importance of examining the generalizability of any posited polygenic risk scores. Conclusions: In conclusion, we provide additional support for and further refine the results of a previously published polygenic risk score for GDM in an ethically unrelated population. Full article
(This article belongs to the Section Omics/Informatics)
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21 pages, 1997 KB  
Article
Genetic and Metabolic Factors of Familial Dysbetalipoproteinemia Phenotype: Insights from a Cross-Sectional Study
by Anastasia V. Blokhina, Alexandra I. Ershova, Anna V. Kiseleva, Evgeniia A. Sotnikova, Marija Zaicenoka, Anastasia A. Zharikova, Yuri V. Vyatkin, Vasily E. Ramensky, Elizaveta A. Novokhatskaya, Anna L. Borisova, Svetlana A. Shalnova, Alexey N. Meshkov and Oxana M. Drapkina
Int. J. Mol. Sci. 2025, 26(15), 7376; https://doi.org/10.3390/ijms26157376 - 30 Jul 2025
Viewed by 573
Abstract
Familial dysbetalipoproteinemia (FD) is a prevalent and highly atherogenic hyperlipoproteinemia associated with the ε2/ε2 APOE genotype or rare APOE variants. The contributions of additional genetic and clinical factors to the FD phenotype remain unclear. We investigated these factors in both autosomal recessive and [...] Read more.
Familial dysbetalipoproteinemia (FD) is a prevalent and highly atherogenic hyperlipoproteinemia associated with the ε2/ε2 APOE genotype or rare APOE variants. The contributions of additional genetic and clinical factors to the FD phenotype remain unclear. We investigated these factors in both autosomal recessive and autosomal dominant forms of FD. Targeted (n = 4666) and exome (n = 194) sequencing were used to identify the ε2/ε2 APOE genotype or rare FD-causative APOE variants. Twenty-four lipid-related genes and forty variants included in a polygenic risk score for hypertriglyceridemia (HTG) were analyzed. FD was defined by the presence of FD variants and triglycerides (TG) ≥ 1.5 mmol/L (main study group). The comparison group consisted of patients with FD variants but TG < 1.5 mmol/L. Univariable and multivariable regression analyses were performed. A total of 71 unrelated subjects were identified (45.1% male, median age 50 years). FD was diagnosed in 52 patients, while 19 had FD variants only. Age (p = 0.019), elevated polygenic risk for HTG (p = 0.001), and the presence of metabolic syndrome components (p = 0.014) were independently associated with the FD phenotype. TG levels were significantly associated with polygenic burden (0.05 mmol/L per percentile), the presence of additional rare lipid-related variants (7.0 mmol/L), and glucose metabolism disorders (3.62 mmol/L), together explaining 30% of TG variance in cross-validated model. These results highlight the interplay of genetic and metabolic factors in FD development and support the integration of HTG genetic risk scores and metabolic control into personalized FD management. Full article
(This article belongs to the Special Issue Genes and Human Diseases: 3rd Edition)
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11 pages, 275 KB  
Article
Polygenic Score for Body Mass Index Is Associated with Weight Loss and Lipid Outcomes After Metabolic and Bariatric Surgery
by Luana Aldegheri, Chiara Cipullo, Natalia Rosso, Eulalia Catamo, Biagio Casagranda, Pablo Giraudi, Nicolò de Manzini, Silvia Palmisano and Antonietta Robino
Int. J. Mol. Sci. 2025, 26(15), 7337; https://doi.org/10.3390/ijms26157337 - 29 Jul 2025
Viewed by 845
Abstract
Metabolic and bariatric surgery (MBS) is an effective treatment for severe obesity, though individual responses vary widely, partly due to genetic predisposition. This study investigates the association of a body mass index (BMI) polygenic score (PGS) with weight loss and metabolic outcomes following [...] Read more.
Metabolic and bariatric surgery (MBS) is an effective treatment for severe obesity, though individual responses vary widely, partly due to genetic predisposition. This study investigates the association of a body mass index (BMI) polygenic score (PGS) with weight loss and metabolic outcomes following surgery. A cohort of 225 patients undergoing MBS was analyzed at baseline (T0), six (T6), and twelve (T12) months, with anthropometric and biochemical parameters recorded at each time point. Total weight loss (TWL) and excess weight loss (EWL) percentages were calculated. PGS was computed using the LDpred-grid Bayesian method. The mean age was 45.9 ± 9.4 years. Males had a higher baseline prevalence of type 2 diabetes (T2D) and comorbidities (p < 0.001). Linear regression analysis confirmed an association between PGS and baseline BMI (p = 0.012). Moreover, mediation analysis revealed that baseline BMI mediated the effect of the PGS on %TWL at T12, with an indirect effect (p-value = 0.018). In contrast, high-density lipoprotein-cholesterol (HDL-C) at T6 and triglycerides (TG) at T12 showed direct associations with the PGS (p-value = 0.004 and p-value = 0.08, respectively), with no significant mediation by BMI. This study showed a BMI-mediated association of PGS with %TWL and a direct association with lipid changes, suggesting its potential integration into personalized obesity treatment. Full article
(This article belongs to the Special Issue Genetic and Molecular Mechanisms of Obesity)
18 pages, 2118 KB  
Article
Screening of Mutant Lines and Varieties/Hybrids of Tomato (Solanum lycopersicum) for Resistance to the Northern Root-Knot Nematode Meloidogyne hapla
by Svetlana Nikolaevna Nekoval, Zhanneta Zaurovna Tukhuzheva, Arina Konstantinovna Churikova, Valentin Valentinovich Ivanov and Oksana Aleksandrovna Maskalenko
Horticulturae 2025, 11(7), 798; https://doi.org/10.3390/horticulturae11070798 - 5 Jul 2025
Viewed by 744
Abstract
Root-knot nematodes, Meloidogyne spp., are widespread phytoparasites that cause a significant reduction in the yield of tomato Solanum lycopersicum. In the Russian Federation, where the use of chemical nematicides is limited due to environmental and toxicological risks, the cultivation of resistant varieties [...] Read more.
Root-knot nematodes, Meloidogyne spp., are widespread phytoparasites that cause a significant reduction in the yield of tomato Solanum lycopersicum. In the Russian Federation, where the use of chemical nematicides is limited due to environmental and toxicological risks, the cultivation of resistant varieties and hybrids remains the most effective and environmentally safe method to control Meloidogyne. In the course of this study, the resistance screening of 20 tomato varieties/hybrids and 21 mutant lines from the collection of the FSBSI FRCBPP to M. hapla was carried out using a comprehensive approach that included morphological and biochemical analysis methods. Resistance was assessed by calculating the gall formation index, the degree of root system damage, and biochemical parameters of fruits—vitamin C content and titratable acidity. In addition, molecular screening was carried out using the SCAR marker Mi23 to identify the Mi-1.2 gene, known as a key factor in resistance to a number of Meloidogyne spp. Although Mi-1.2 is not typically associated with resistance to M. hapla, all genotypes carrying this gene showed phenotypic resistance. This unexpected correlation suggests the possible involvement of Mi-associated or parallel mechanisms and highlights the need for further investigation into noncanonical resistance pathways. It was found that when susceptible genotypes were infected with M. hapla, there was a tendency for the vitamin C content to decrease, while resistant lines retained values close to the control. The presence of the Mi-1.2 gene was confirmed in 9.5% of samples. However, the phenotypic resistance of some lines, such as Volgogradets, which do not contain a marker for the Mi-1.2 gene, indicates a polygenic nature of resistance, alternative genetic mechanisms, or the possible influence of epigenetic mechanisms. The obtained data highlight the potential of using the identified resistant genotypes in breeding programs and the need for further studies of the molecular mechanisms of resistance, including the search for new markers specific to M. hapla, to develop effective strategies for tomato protection in sustainable agriculture. Full article
(This article belongs to the Special Issue Sustainable Management of Pathogens in Horticultural Crops)
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23 pages, 1348 KB  
Review
The Genome Era of Forage Selection: Current Status and Future Directions for Perennial Ryegrass Breeding and Evaluation
by Jiashuai Zhu, Kevin F. Smith, Noel O. Cogan, Khageswor Giri and Joe L. Jacobs
Agronomy 2025, 15(6), 1494; https://doi.org/10.3390/agronomy15061494 - 19 Jun 2025
Cited by 1 | Viewed by 1244
Abstract
Perennial ryegrass (Lolium perenne L.) is a cornerstone forage species in temperate dairy systems worldwide, valued for its high yield potential, nutritive quality, and grazing recovery. However, current regional evaluation systems face challenges in accurately assessing complex traits like seasonal dry matter [...] Read more.
Perennial ryegrass (Lolium perenne L.) is a cornerstone forage species in temperate dairy systems worldwide, valued for its high yield potential, nutritive quality, and grazing recovery. However, current regional evaluation systems face challenges in accurately assessing complex traits like seasonal dry matter yield due to polygenic nature, environmental variability, and lengthy evaluation cycles. This review examines the evolution of perennial ryegrass evaluation systems, from regional frameworks—like Australia’s Forage Value Index (AU-FVI), New Zealand’s Forage Value Index (NZ-FVI), and Ireland’s Pasture Profit Index (PPI)—to advanced genomic prediction (GP) approaches. We discuss prominent breeding frameworks—F2 family, Half-sib family, and Synthetic Population—and their integration with high-throughput genotyping technologies. Statistical models for GP are compared, including marker-based, kernel-based, and non-parametric approaches, highlighting their strengths in capturing genetic complexity. Key research efforts include representative genotyping approaches for heterozygous populations, disentangling endophyte–host interactions, extending prediction to additional economically important traits, and modeling genotype-by-environment (G × E) interactions. The integration of multi-omics data, advanced phenotyping technologies, and environmental modeling offers promising avenues for enhancing prediction accuracy under changing environmental conditions. By discussing the combination of regional evaluation systems with GP, this review provides comprehensive insights for enhancing perennial ryegrass breeding and evaluation programs, ultimately supporting sustainable productivity of the dairy industry in the face of climate challenges. Full article
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16 pages, 3469 KB  
Article
Phenotypic Characters and Inheritance Tendency of Agronomic Traits in F1 Progeny of Pear
by Xiaojie Zhang, Mengyue Tang, Jiamei Li, Yue Chi, Kexin Wang, Jianying Peng and Yuxing Zhang
Plants 2025, 14(10), 1491; https://doi.org/10.3390/plants14101491 - 16 May 2025
Cited by 1 | Viewed by 742
Abstract
Studying fruit genetic trends, heterosis, and growth traits in pear hybrid progeny provides the foundation for variety breeding. The aim of this research is to reveal the trait performance of the hybrid progeny of Chinese white pear and Western pear and provide a [...] Read more.
Studying fruit genetic trends, heterosis, and growth traits in pear hybrid progeny provides the foundation for variety breeding. The aim of this research is to reveal the trait performance of the hybrid progeny of Chinese white pear and Western pear and provide a theoretical basis for other breeders to predict the trait performance of their hybrid progeny when selecting Eastern pear and Western pear as parents. Our research team constructed a ‘Yuluxiang’ × ‘Xianghongli’ interspecific hybrid population in 2015, and in 2023, we conducted a two-year investigation of 16 traits in 140 hybrid progeny, including 11 fruit traits and 5 growth traits, and analyzed and compared the genetic variation and heterosis of traits, as well as the correlation between various traits. The results showed that the hybrid progeny was widely segregated for single fruit weight (FW), soluble solid (SS) content, and titratable acid (TA) content and conformed to a normal distribution, with quantitative genetic traits under polygenic control. The highest two-year coefficients of variation for TA were 54.42% in 2023 and 39.17% in 2024. A genetic trend of decreasing FW was observed, which was greatly influenced by the male sex. The ratio of soft soluble flesh to crispy flesh was 1:1, and the gene controlling this trait may be a quality trait controlled by a single gene. The traits that showed transgressive heterosis for two years included fruit longitudinal diameter (FLoD), fruit shape index (FSI), and TA, and those that showed negative heterosis included FW, SS, leaf longitudinal diameter (LLoD), and leaf lateral diameter (LLaD). Correlation analysis indicated that the progeny of crosses in this combination, which had red fruit skin, may also present red early flowering color (EFC) and young leaf color (YLC), reddish brown annual branch color (ABC), and lower FSI, fruit stalk length (FSL), LLaD, and TA. Thus, at the seedling stage, individuals with red-colored fruit may be screened by observing the color of young leaves and young stems and the lateral diameter of the leaves. Principal component analysis showed that among the 16 traits included in six principal components, peel color (PC), FLoD, 2024SS, fruit tape (FT), and FSI were the main factors causing differences in fruit phenotypes. This study systematically elucidated the genetic trends of agronomic traits in pears and will provide a theoretical basis for the selection of parents and early selection of hybrid progeny in pear hybrid breeding. Full article
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15 pages, 2554 KB  
Article
Major Gene with Polygene Inheritance Analysis of Prostrate Growth Habit in Hybrids of Chrysanthemum yantaiense × C. indicum
by Dawei Li, Yuxian Xu, Yuchao Tang, Tongjun Zhou, Hai Li, Ziyu Guo, Yilin Liang, Yuxin Wang, Yuyuan Chen and Ming Sun
Plants 2025, 14(9), 1338; https://doi.org/10.3390/plants14091338 - 29 Apr 2025
Viewed by 715
Abstract
Plant architecture is a crucial trait for ornamental plants. Chrysanthemum with prostrate growth habit is a novel cultivar group of ground-cover chrysanthemum, which have high ornamental value, strong lodging resistance, and outstanding landscape greening capability. To explore the genetic mechanism underlying the prostrate [...] Read more.
Plant architecture is a crucial trait for ornamental plants. Chrysanthemum with prostrate growth habit is a novel cultivar group of ground-cover chrysanthemum, which have high ornamental value, strong lodging resistance, and outstanding landscape greening capability. To explore the genetic mechanism underlying the prostrate growth habit in chrysanthemum, we used tetraploid prostrate-type Chrysanthemum yantaiense as the female parent and erect-type Chrysanthemum indicum as the male parent to produce four generations (P1, P2, F1, F2). Five traits related to prostrate growth habit in chrysanthemum were investigated including plant height (PH), crown width of the plant (CP), creeping index (CI), gravitropic set-point angle (GSA), and growth habit (GH). The major gene plus polygene mixed inheritance analysis was conducted on five traits across four generations over two years. For the five traits, the coefficients of variation (CVs) were wide-ranging and high (16.64–42.75%), with the PH having the highest CV among them. Genetic analysis revealed that PH conformed to the additive-dominant-epistatic polygene model (C-0) and the model of two equally dominant major genes plus additive-dominant polygene (E-5). The most suitable genetic model for CI was an additive-dominant major gene plus additive-dominant-epistatic polygene model (D-0). The best-fit models for CP and GH were both C-0. For GSA, the best-fit models were E-4 and C-0. Additionally, it appeared that both genetic and environmental factors influenced the prostrate growth habit, as the heritability of major genes and polygenes was less than 50%. This study can serve as a theoretical foundation for the mapping of quantitative trait loci (QTLs) and further exploration of the genetic mechanisms underlying plant architecture in chrysanthemum. Full article
(This article belongs to the Special Issue Flower Germplasm Resources and Genetic Breeding, 2nd Edition)
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11 pages, 1365 KB  
Article
Intrafamilial Phenotypic Variability of the FGFR1 p.Cys277Tyr Variant: A Case Report and Review of the Literature
by Anna Szoszkiewicz, Anna Sowińska-Seidler, Karolina Gruca-Stryjak and Aleksander Jamsheer
Genes 2025, 16(5), 495; https://doi.org/10.3390/genes16050495 - 26 Apr 2025
Viewed by 1231
Abstract
Background: Split-hand/foot malformation (SHFM) is a rare congenital limb anomaly defined by the absence or hypoplasia of the central rays of the autopod. SHFM occurs as an isolated entity or part of genetic syndromes with several causative copy-number variations or monogenic alterations known [...] Read more.
Background: Split-hand/foot malformation (SHFM) is a rare congenital limb anomaly defined by the absence or hypoplasia of the central rays of the autopod. SHFM occurs as an isolated entity or part of genetic syndromes with several causative copy-number variations or monogenic alterations known to be involved in the disease pathomechanism. On the other hand, cleft lip/palate (CL/P) usually results from polygenic and environmental factors, with the complex interplay of both leading to this malformation. Pathogenic variants in FGFR1 have been linked to phenotypically distinct disorders, including Hartsfield syndrome, Kallmann syndrome, Jackson–Weiss syndrome, osteoglophonic dysplasia, and Pfeiffer syndrome. Although pathogenic variants in FGFR1 can contribute to syndromic SHFM or CL/P, their role in isolated SHFM or CL remains poorly described in the literature. Methods: We conducted targeted next-generation sequencing (NGS) in the proband with SHFM, followed by segregation analysis in the family members. Results: In this study, we report an index patient presenting with isolated SHFM and his brother with CL and facial dysmorphism, as well as their father with isolated hyposmia. Targeted next-generation sequencing revealed a previously reported heterozygous missense pathogenic variant in FGFR1 (c.830G>A; p.Cys277Tyr) in both affected siblings and their hyposmic father. Conclusions: This study expands the phenotypic spectrum associated with FGFR1 pathogenic variants, emphasizing their involvement in non-syndromic SHFM and CL or isolated hyposmia. Our findings highlight the importance of considering FGFR1 in the molecular diagnosis of isolated SHFM or orofacial clefting, point to the high intrafamilial variability of FGFR1 pathogenic variants, and demonstrate the diagnostic value of targeted NGS in rare congenital malformations. Full article
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14 pages, 289 KB  
Article
Circulating Bilirubin Levels, but Not Their Genetic Determinants, Are Inversely Associated with Steatotic Liver Disease in Adolescents
by José Patricio Miranda, Juan Cristóbal Gana, Gigliola Alberti, Karen Galindo, Ana Pereira and José Luis Santos
Int. J. Mol. Sci. 2025, 26(7), 2980; https://doi.org/10.3390/ijms26072980 - 25 Mar 2025
Viewed by 824
Abstract
Epidemiologic studies suggest that elevated plasma unconjugated bilirubin confer protection against steatotic liver disease (SLD) in adults. However, evidence supporting this protective role in adolescents remains limited. We aimed to assess the association between serum bilirubin levels and their genetic determinants in protecting [...] Read more.
Epidemiologic studies suggest that elevated plasma unconjugated bilirubin confer protection against steatotic liver disease (SLD) in adults. However, evidence supporting this protective role in adolescents remains limited. We aimed to assess the association between serum bilirubin levels and their genetic determinants in protecting against SLD in Chilean adolescents. We conducted a cross-sectional study with 704 adolescents aged 15.4 ± 1 years (52% girls) of the Chilean Growth and Obesity Cohort Study. Ultrasonography echogenicity was used to diagnose SLD. We measured Z-scores of body mass index (z-BMI), total bilirubin (TB), and the genetic determinants of bilirubin (including rs887829 genotypes of UGT1A1 and bilirubin polygenic scores). Multiple logistic regression models evaluated the associations between standardized TB and its genetic determinants with SLD. We found that 1-SD of standardized plasma TB was significantly associated with a 30% reduction in the likelihood of SLD after adjustment by sex, age, z-BMI, and ethnicity (OR = 0.7; 95% CI = 0.50–0.96; p = 0.03). No significant associations were found among the rs887829 genotypes, bilirubin polygenic scores, and SLD in logistic regression models adjusted by covariates. Increased circulating bilirubin levels are unlikely causally associated with protection against SLD, and the cross-sectional association could be due to unmeasured confounding. Full article
(This article belongs to the Special Issue Bilirubin: Health Challenges and Opportunities)
11 pages, 462 KB  
Article
Demographic, Premorbid, and Clinical Characteristics of Schizophrenia Spectrum Patients with High and Low Polygenic Liability to the Disorder
by Margarita Alfimova, Marina Gabaeva, Tatyana Lezheiko, Victoria Plakunova, Yulia Chaika and Vera Golimbet
Diseases 2025, 13(3), 66; https://doi.org/10.3390/diseases13030066 - 21 Feb 2025
Cited by 1 | Viewed by 743
Abstract
Background/Objectives: Schizophrenia is a clinically heterogeneous complex disorder with a substantial polygenic basis. The discovery of phenotypes indexing genetic differences advances research into the schizophrenia etiology but has proven to be challenging. The study aimed to further clarify the relationships of schizophrenia polygenic [...] Read more.
Background/Objectives: Schizophrenia is a clinically heterogeneous complex disorder with a substantial polygenic basis. The discovery of phenotypes indexing genetic differences advances research into the schizophrenia etiology but has proven to be challenging. The study aimed to further clarify the relationships of schizophrenia polygenic risk scores (SZ-PRSs) with a comprehensive array of schizophrenia antecedents and presentations using a culturally and ethnically homogeneous sample of schizophrenia spectrum patients. Methods: The top and bottom deciles (n = 172) of the SZ-PRS distribution in a group of 861 patients were compared on information derived from medical records using logistic regression. Results: High SZ-PRSs were associated with female sex, family history of a wide range of neuropsychiatric conditions, moderately poor premorbid social and cognitive adjustment in childhood, the schizophrenia diagnosis, and positive and “abnormal” psychomotor symptoms. The low-SZ-PRS group demonstrated an accumulation of both individuals with milder forms of SZ spectrum disorders and those with severe premorbid abnormalities in the social, cognitive, and neurological domains. Conclusions: The results highlight moderately poor premorbid social and cognitive adjustment as characteristic manifestations of the polygenic component of the schizophrenia etiology and provide the first piece of PRS-based evidence for the long-standing idea of a higher liability threshold in women. The presence of milder and severe cases in the bottom SZ-PRS decile, suggesting its etiological heterogeneity, might be an important source of the inconsistency in the previous research on SZ-PRSs’ relationship with schizophrenia phenotypes and should be considered in future studies. Full article
(This article belongs to the Section Neuro-psychiatric Disorders)
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11 pages, 1275 KB  
Article
Fleece-Lined Whelping Pools Associated with Reduced Incidence of Canine Hip Dysplasia in a Guide Dog Program
by Lynna C. Feng, Alexandra Philippine, Elizabeth Ball-Conley and Sarah-Elizabeth Byosiere
Animals 2025, 15(2), 152; https://doi.org/10.3390/ani15020152 - 9 Jan 2025
Viewed by 4824
Abstract
Using genetic selection, Guide Dogs for the Blind (GDB) has reduced the incidence rate of canine hip dysplasia (CHD). However, given that CHD is polygenic and multifactorial, environmental factors may impact the expression of this developmental condition. The objective of this original, correlational [...] Read more.
Using genetic selection, Guide Dogs for the Blind (GDB) has reduced the incidence rate of canine hip dysplasia (CHD). However, given that CHD is polygenic and multifactorial, environmental factors may impact the expression of this developmental condition. The objective of this original, correlational research was to investigate the relationship between the substrate in the whelping pool used from birth to 3 weeks of age and CHD diagnosis. This retrospective study included 5649 dogs (Labrador Retrievers, Golden Retrievers, and Labrador–Golden Retriever crosses) at GDB. A total of 2785 dogs were whelped between 1 July 2012 and 28 November 2015, when the whelping pools were lined with newspaper, and 2864 dogs were whelped between 5 March 2016 and 29 December 2019, when the whelping pools were lined with fleece. Bayesian regression modeling of the CHD diagnoses and PennHIP distraction index scores identified that dogs in the fleece group had a lower risk for CHD diagnosis but similar PennHIP scores compared to the newspaper group. Golden Retrievers had the highest risk of CHD diagnosis and PennHIP scores, followed by Labrador–Golden Retriever crosses and finally Labrador Retrievers, with the lowest risk of CHD diagnosis and PennHIP scores. No sex differences were identified for CHD diagnosis, but males had lower PennHIP scores than females. These results provide correlational evidence that housing-related environmental factors during the first three weeks of development—specifically, the substrate in the whelping pool—are associated with lifelong orthopedic health. Full article
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10 pages, 571 KB  
Article
Sleep Genetics and Cognitive Changes over Time: The Moderating Effect of Age and the Role of Brain
by Angeliki Tsapanou, Seonjoo Lee, Silvia Chapman, Niki Mourtzi, Christian Habeck and Yaakov Stern
Genes 2025, 16(1), 21; https://doi.org/10.3390/genes16010021 - 26 Dec 2024
Viewed by 2485
Abstract
Background: Sleep plays a crucial role in cognitive performance and cognitive changes in aging. In the current study, we investigated the role of sleep duration genetics in cognitive changes over time and the moderating effect of age. Methods: Participants were drawn from the [...] Read more.
Background: Sleep plays a crucial role in cognitive performance and cognitive changes in aging. In the current study, we investigated the role of sleep duration genetics in cognitive changes over time and the moderating effect of age. Methods: Participants were drawn from the Reference Abilities Neural Network and the Cognitive Reserve studies of Columbia University. Each participant underwent an evaluation of sleep function and an extensive neuropsychological assessment. Published GWAS summary statistics from a polygenic score for sleep duration (Sleep PGI) were used to derive Sleep PGI in our study. We examined whether this Sleep PGI is associated with cognitive changes over a 5-year follow-up and if age moderates this effect. Analysis was performed after first being adjusted for age group (young: 20–44; middle: 45–64; old: 65–80), sex, education, the first four principal components, intracranial volume (ICV), mean cortical thickness, and total gray matter volume. We included ICV, mean thickness, and total gray matter volumes as time-varying covariates. We further included interactions of time with age and the first four PCs. Results: A total of 96 white-only participants were included, aged 24 to 78 years old. In the fully adjusted model, age-specific analysis showed that in younger individuals, higher Sleep PGI was associated with lower rates of cognitive decline in speed of processing. Conclusion: Genetic variants associated with sleep duration significantly influence performance in speed of processing, with age playing a critical moderating role, over and above brain morphometry. A genetic predisposition for longer sleep duration can work as a protective factor against decline in the speed of processing in young adults. Full article
(This article belongs to the Section Human Genomics and Genetic Diseases)
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14 pages, 2451 KB  
Article
Inbreeding and Gallbladder Cancer Risk: Homozygosity Associations Adjusted for Indigenous American Ancestry, BMI, and Genetic Risk of Gallstone Disease
by Francisco Ceballos, Felix Boekstegers, Dominique Scherer, Carol Barahona Ponce, Katherine Marcelain, Valentina Gárate-Calderón, Melanie Waldenberger, Erik Morales, Armando Rojas, César Munoz, Javier Retamales, Gonzalo de Toro, Allan Vera Kortmann, Olga Barajas, María Teresa Rivera, Analía Cortés, Denisse Loader, Javiera Saavedra, Lorena Gutiérrez, Alejandro Ortega, Maria Enriqueta Bertrán, Leonardo Bartolotti, Fernando Gabler, Mónica Campos, Juan Alvarado, Fabricio Moisán, Loreto Spencer, Bruno Nervi, Daniel Carvajal-Hausdorf, Héctor Losada, Mauricio Almau, Plinio Fernández, Jordi Olloquequi, Pamela Salinas and Justo Lorenzo Bermejoadd Show full author list remove Hide full author list
Cancers 2024, 16(24), 4195; https://doi.org/10.3390/cancers16244195 - 17 Dec 2024
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Abstract
Latin Americans have a rich genetic make-up that translates into heterogeneous fractions of the autosomal genome in runs of homozygosity (FROH) and heterogeneous types and proportions of indigenous American ancestry. While autozygosity has been linked to several human diseases, very little [...] Read more.
Latin Americans have a rich genetic make-up that translates into heterogeneous fractions of the autosomal genome in runs of homozygosity (FROH) and heterogeneous types and proportions of indigenous American ancestry. While autozygosity has been linked to several human diseases, very little is known about the relationship between inbreeding, genetic ancestry, and cancer risk in Latin Americans. Chile has one of the highest incidences of gallbladder cancer (GBC) in the world, and we investigated the association between inbreeding, GBC, gallstone disease (GSD), and body mass index (BMI) in 4029 genetically admixed Chileans. We calculated individual FROH above 1.5 Mb and weighted polygenic risk scores for GSD, and applied multiple logistic regression to assess the association between homozygosity and GBC risk. We found that homozygosity was due to a heterogeneous mixture of genetic drift and consanguinity in the study population. Although we found no association between homozygosity and overall GBC risk, we detected interactions of FROH with sex, age, and genetic risk of GSD that affected GBC risk. Specifically, the increase in GBC risk per 1% FROH was 19% in men (p-value = 0.002), 30% in those under 60 years of age (p-value = 0.001), and 12% in those with a genetic risk of GSD above the median (p-value = 0.01). The present study highlighted the complex interplay between inbreeding, genetic ancestry, and genetic risk of GSD in the development of GBC. The applied methodology and our findings underscored the importance of considering the population-specific genetic architecture, along with sex- and age-specific effects, when investigating the genetic basis of complex traits in Latin Americans. Full article
(This article belongs to the Section Cancer Epidemiology and Prevention)
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Article
The Joint Contribution of Childhood Exposure to Parental Smoking and Genetic Susceptibility to Smoking to Epigenetic Age Acceleration in Late Adulthood: The Health and Retirement Study
by Tingting Liu, Yixi Sun, Ruiyuan Zhang and Changwei Li
Future 2024, 2(4), 185-193; https://doi.org/10.3390/future2040015 - 6 Dec 2024
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Abstract
The impact of childhood exposure to parental smoking on epigenetic age acceleration (EAA) in later life has not been thoroughly investigated. This study investigates the relationship while considering genetic susceptibility to smoking. We analyzed data from 3102 participants in the Health and Retirement [...] Read more.
The impact of childhood exposure to parental smoking on epigenetic age acceleration (EAA) in later life has not been thoroughly investigated. This study investigates the relationship while considering genetic susceptibility to smoking. We analyzed data from 3102 participants in the Health and Retirement Study (HRS) who also participated in the 2016 Venous Blood Study and the 2015–2017 Life History Mail Survey. Self-reported measures included childhood parental smoking exposure and smoking status in late adulthood. We utilized five epigenetic clocks—HorvathAA, HannumAA, GrimAA, PhenoAA, and DunedinAA—and assessed genetic susceptibility with a polygenic risk score (PRS) for smoking initiation, categorized into tertiles. We regressed the clocks against chronological age to derive EAA residuals. Associations between childhood exposure and EAA were examined in the overall sample and by PRS tertiles, stratified by race. The model controlled for age, sex, education, smoking, alcohol consumption, body mass index, and CESD scores. Significant associations were found between childhood exposure to parental smoking and the EAA measured by GrimAA (β = 0.98; p < 0.001) and DunedinAA (β = 0.01; p = 0.002) among White participants, with stronger effects in those with a high PRS. Similar patterns were observed in Black participants, highlighting the importance of preventing secondhand smoke exposure in children. Full article
(This article belongs to the Special Issue Feature Papers in Future)
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