OBJECTIVES: To investigate the relationship between the polygenic risks for various psychiatric disorders and clinical and neuropsychological characteristics in children with attention-deficit/hyperactivity disorder (ADHD). METHODS: Using a cross-sectional design, 285 children with ADHD and 107 healthy controls were assessed using the Child Behavior Checklist, the Behavior Rating Inventory of Executive Function for parents, the Wechsler Intelligence Scale for Children, Fourth Edition, and the Cambridge Neuropsychological Test Automated Battery. Blood samples were collected for genetic data. Polygenic risk scores (PRSs) for various psychiatric disorders were calculated using the PRSice-2 software. RESULTS: Compared with the healthy controls, the children with ADHD displayed significantly higher PRSs for ADHD, major depressive disorder, anxiety disorder, and obsessive-compulsive disorder (P<0.05). In terms of daily-life executive function, ADHD-related PRS was significantly correlated with the working memory factor; panic disorder-related PRS was significantly correlated with the initiation factor; bipolar disorder-related PRS was significantly correlated with the shift factor; schizophrenia-related PRS was significantly correlated with the inhibition, emotional control, initiation, working memory, planning, organization, and monitoring factors (P<0.05). The PRS related to anxiety disorders was negatively correlated with total IQ and processing speed index (P<0.05). The PRS related to obsessive-compulsive disorder was negatively correlated with the processing speed index and positively correlated with the stop-signal reaction time index of the stop-signal task (P<0.05). CONCLUSIONS PRSs for various psychiatric disorders are closely correlated with the behavioral and cognitive characteristics in children with ADHD, which provides more insights into the heterogeneity of ADHD.
Humans ; Attention Deficit Disorder with Hyperactivity/genetics* ; Child ; Male ; Female ; Cross-Sectional Studies ; Neuropsychological Tests ; Multifactorial Inheritance ; Adolescent ; Mental Disorders/etiology* ; Executive Function ; Genetic Risk Score

BACKGROUND: A polygenic risk score (PRS) derived from 112 single-nucleotide polymorphisms (SNPs) for gastric cancer has been reported in Chinese populations (PRS-112). However, its performance in other populations is unknown. A functional PRS (fPRS) using functional SNPs (fSNPs) may improve the generalizability of the PRS across populations with distinct ethnicities. METHODS: We performed functional annotations on SNPs in strong linkage disequilibrium (LD) with the 112 previously reported SNPs to identify fSNPs that affect protein-coding or transcriptional regulation. Subsequently, we constructed an fPRS based on the fSNPs by using the LDpred2-infinitesimal model and then analyzed the performance of the PRS-112 and fPRS in the risk prediction of gastric cancer in 457,521 European participants of the UK Biobank cohort. Finally, the performance of the fPRS in combination with lifestyle factors were evaluated in predicting the risk of gastric cancer. RESULTS: During 4,582,045 person-years of follow-up with a total of 623 incident gastric cancer cases, we found no significant association between the PRS-112 and gastric cancer risk in the European population (hazard ratio [HR] = 1.00 [95% confidence interval (CI) 0.93-1.09], P = 0.846). We identified 125 fSNPs, including seven deleterious protein-coding SNPs and 118 regulatory non-coding SNPs, and used them to construct the fPRS-125. Our result showed that the fPRS-125 was significantly associated with gastric cancer risk (HR = 1.11 [95% CI, 1.03-1.20], P = 0.009). Compared to participants with a low fPRS-125 (bottom quintile), those with a high fPRS-125 (top quintile) had a higher risk of incident gastric cancer (HR = 1.43 [95% CI, 1.12-1.84], P = 0.005). Moreover, we observed that participants with both an unfavorable lifestyle and a high genetic risk had the highest risk of incident gastric cancer (HR = 4.99 [95% CI, 1.55-16.10], P = 0.007) compared to those with both a favorable lifestyle and a low genetic risk. CONCLUSION These results indicate that the fPRS-125 derived from fSNPs may act as an indicator to measure the genetic risk of gastric cancer in the European population.
Humans ; Prospective Studies ; Stomach Neoplasms/genetics* ; Genetic Predisposition to Disease/genetics* ; Risk Factors ; Multifactorial Inheritance/genetics* ; Polymorphism, Single Nucleotide/genetics* ; Genome-Wide Association Study

The research team on the National Key Scientific Program of China: "Transcriptomic regulation and molecular mechanism research of polygenic tumor at different stages" has focused on the field of transcriptomics of 4 common polygenic tumors, including nasopharyngeal carcinoma(NPC), breast cancer, colorectal cancer, and glioma. Extensive laboratory work has been carried out on the expression and regulation of tumor transcriptomics; identification of tumor suppressor/susceptible genes; mechanism of tumor epigenetics including miRNAs, and comparative study of specific gene/protein cluster of tumor transcriptomics and proteomics. Genes including SPLUNC1, LTF, BRD7, NOR1, BRCA1/2, PALB2, AF1Q, SOX17, NGX6, SOX7, and LRRC4 have been identified as the key transcriptional regulation genes during the stage of tumor initiation and invasion. Accordingly,the NPC gene signal regulation network of "SPLUNC1-miR-141-target genes", the breast cancer interaction signal pathway of "miR-193b-uPA",the glioma signal network of "miR-381- LRRC4-MEK/ERK/AKT", and the miRNA-target gene network of colorectal cancer metastasis related gene NGX6 have been thoroughly elucidated. These fruitful Results imply that the changes of key molecules in crucial signal pathway will cause severe dysfunction in signal transduction and gene regulation network in polygenic tumors, indicating that in the category of pathogenesis,these tumors may further classify as the "Disease of gene signal transduction and gene regulation network disorder". The researches have laid solid foundation for revealing the molecular mechanism and transcriptomic regulation of polygenic tumors at different stages.
Animals ; Brain Neoplasms ; genetics ; pathology ; Breast Neoplasms ; genetics ; pathology ; Colorectal Neoplasms ; genetics ; pathology ; Gene Expression Regulation, Neoplastic ; Gene Regulatory Networks ; Glioma ; genetics ; pathology ; Humans ; MicroRNAs ; genetics ; Multifactorial Inheritance ; Nasopharyngeal Neoplasms ; genetics ; pathology ; Neoplasm Proteins ; genetics ; Neoplasm Staging ; Neoplasms ; genetics ; Transcription, Genetic ; Transcriptome ; Tumor Suppressor Proteins ; genetics

OBJECTIVETo explore the effects of genetic factors on the occurrence of allergic rhinitis (AR).

METHODSThe morbidity rate of AR was surveyed by multistage sampling among 95 300 individuals (23,825 families) in Natong region, Jiangsu province. And a genetic epidemiologic investigation on AR was carried out to estimate the segregation ratio and heritability (h2) of AR by the methods of Li-Mantel-Gart and Falconer respectively.

RESULTSThe morbidity rate of AR in Natong region was 1.20% (Male 1.21%, Female 1.18%, no statistical significance between them); By the data of the AR ancestry, the segregation ratio of AR in Nantong region was 0.078, significantly less than 0.25, and the genetic model belonged to polygenetics. The 1st, the 2nd, and the 3rd generation h2 of AR were (82.6 +/- 2.19)%, (80.8 +/- 2.93)%, (78.4 +/- 7.04)%. The h2 of AR was (81.86 +/- 1.70)%. In the ancestry of AR, the morbidity rate of the 1st generation with AR was 12.11%; the 2nd generation with AR was 5.12%; the 3rd generation with AR was 2.75%; and the morbidity rate of AR in general population was 1.20%.

CONCLUSIONSThe heredity in family with AR is obvious. Several genes plus the environmental factors may cause AR, which accords with the characteristics of the polygene heredity disease.

China ; epidemiology ; Female ; Humans ; Male ; Multifactorial Inheritance ; Prevalence ; Rhinitis, Allergic, Perennial ; epidemiology ; genetics ; Rhinitis, Allergic, Seasonal ; epidemiology ; genetics

Omics docking study for polygenic inheritance tumors has become an important strategy in oncology research. This review focuses on the conceptions and technologies of omics, and puts forward the central contents and omics docking for polygenic inheritance tumor to reveal the role of molecular changes at different stages of polygenic inheritance tumor at multidisciplinary and multilayer level. It is a new strategy to explore the mechanism of tumor carcinogenesis, and to regulate the network, key molecules, and drug target by combined biology effects.
Carrier Proteins ; biosynthesis ; genetics ; Genomics ; methods ; Glycoproteins ; biosynthesis ; genetics ; Humans ; Membrane Proteins ; biosynthesis ; genetics ; Multifactorial Inheritance ; genetics ; Neoplasms ; genetics ; metabolism ; Phosphoproteins ; biosynthesis ; genetics ; Proteomics ; methods ; Tumor Suppressor Proteins ; biosynthesis ; genetics

OBJECTIVETo study the method for measuring familial correlations of quantitative trait and analyzing family data set of body height.

METHODSGeneralized estimating equation 2 (GEE2) was employed to estimating both regression coefficients and the familial correlation. Analyses was carried out on software MAREG. A example from height pedigrees illustrated the method.

RESULTSGEE2 provided robust estimations of regression coefficients and familial correlations simultaneously. In body height the correlations between parents and offspring (r = 0.459) and between siblings (r = 0.671) were significantly higher than those between two parents (r = 0.184) after adjusting gender, residence and birth age. Of the same types of relative pairs, the correlation between pairs with individuals of the same gender (eg. father-son r = 0.603, mother-daughter r = 0.456, male sibling r = 0.947, female sibling r = 0.681) was higher than those individuals of different gender (eg father-daughter r = 0.431, mother-son r = 0.364, sibling with different gender r = 0.530).

CONCLUSIONGEE2 should be considered a standard method for the investigation of familial aggregation due to its flexibility and robustness.

Adult ; Body Height ; genetics ; Female ; Humans ; Male ; Middle Aged ; Models, Genetic ; Models, Statistical ; Multifactorial Inheritance ; Nuclear Family ; Pedigree ; Quantitative Trait Loci ; Quantitative Trait, Heritable ; Regression Analysis ; Risk Factors ; Sex Factors