Search

Genetic liability for schizophrenia is associated with psychopathology in early life. It is not clear if these associations are time dependent during childhood, nor if they are specific across different forms of psychopathology. Using genotype and questionnaire data on children (N = 15 105) from the Norwegian Mother, Father and Child Cohort Study, we used schizophrenia polygenic risk scores to test developmental stability in associations with measures of emotional and behavioral problems between 18 months and 5 years, and domain specificity in associations with symptoms of depression, anxiety, conduct problems, oppositionality, inattention, and hyperactivity at 8 years. We then sought to identify symptom profiles—across development and domains—associated with schizophrenia polygenic liability. We found evidence for developmental stability in associations between schizophrenia polygenic risk scores and emotional and behavioral problems, with the latter being mediated specifically via the rate of change in symptoms (β slope = 0.032; 95% CI: 0.007–0.057). At age 8, associations were better explained by a model of symptom-specific polygenic effects rather than effects mediated via a general psychopathology factor or by domain-specific factors. Overall, individuals with higher schizophrenia polygenic risk scores were more likely (OR = 1.310 [95% CIs: 1.122–1.528]) to have a profile of increasing behavioral and emotional symptoms in early childhood, followed by elevated symptoms of conduct disorder, oppositionality, hyperactivity, and inattention by age 8. Schizophrenia-associated alleles are linked to specific patterns of early-life psychopathology. The associations are small, but findings of this nature can help us better understand the developmental emergence of schizophrenia. [ABSTRACT FROM AUTHOR]

Background: Several single-nucleotide variants (SNVs) in collagen genes have been reported as predisposing factors for anterior cruciate ligament (ACL) tears. However, the evidence is conflicting and does not support a clear association between genetic variants and risk of ACL ruptures. Purpose: To assess the association of previously identified candidate SNVs in genes encoding for collagen and the risk of ACL injury in a population of elite female athletes from high-risk team sports. Study Design: Cohort study; Level of evidence, 2. Methods: A total of 851 female Norwegian and Finnish elite athletes from team sports were included from 2007 to 2011. ACL injuries acquired before inclusion in the cohort were registered by interview. The participants were followed prospectively through 2015 to record new complete ACL injuries. Six selected SNVs were genotyped (COL1A1: rs1800012, rs1107946; COL3A1: rs1800255; COL5A1: rs12722, rs13946; COL12A1: rs970547). Results: No associations were found between ACL rupture and the SNVs tested. Conclusion: The study does not support a role of the 6 selected SNVs in genes encoding for collagen proteins as risk factors for ACL injury. Clinical Relevance: Genetic profiling to identify athletes at high risk for ACL rupture is not yet feasible. [ABSTRACT FROM AUTHOR]

Objective. The MHC exerts the greatest contribution to RA susceptibility, where certain HLA-DRB1 alleles confer the greatest risk. Interestingly, there is evidence for more risk factors in the MHC with regions surrounding the HLA class I loci, but whether these antigen-presenting loci could be causal risk variants has not been directly investigated. In this study we investigate the HLA association by direct genotyping of the HLA loci.Methods. Nine hundred and fifty RA patients and 933 healthy controls were genotyped for HLA-A, -B and -C. Eleven single-nucleotide polymorphisms (SNPs) and one insertion/deletion in the MHC were also included. Conditional logistic regression analyses were performed separately in ACPA-positive and -negative RA to identify the strongest susceptibility locus and additional risk loci.Results. In ACPA-positive RA, the most significantly associated locus was HLA-DRB1 (P = 1.58 × 10−54), with SE alleles being predisposing. After controlling for HLA-DRB1, the HLA-C locus was found to confer susceptibility (P = 2.32 × 10−9), particularly, the HLA-C*03 allele. Also, in ACPA-negative RA, HLA-DRB1 was the most significant locus (P = 7.22 × 10−9), but with other risk alleles (particularly DRB1*03). A possible independent involvement of HLA-C was also observed for ACPA-negative RA (P = 0.02).Conclusion. HLA-DRB1 was the major MHC risk locus in both ACPA-positive and ACPA-negative RA, but with allelic risk heterogeneity. Joint analyses of the HLA class I loci together with previously proposed SNP associations pointed at HLA-C as a second susceptibility locus in ACPA-positive RA. [ABSTRACT FROM PUBLISHER]

We studied the impact of genetic and traditional risk factors for type 2 diabetes in a large, population-based study from Nord-Trøndelag county in Norway (HUNT), in both cross-sectional and prospective design. Material and methods . 65,905 individuals participated in the HUNT study. We studied a randomly selected group of 869 individuals with self-reported diabetes or non-fasting serum glucose ≥11.1 mmol/L and 2,080 non-diabetic control subjects with non-fasting serum glucose <5.5 mmol/L. Four candidate polymorphisms in the three genes TCF7L2 (rs12255372 and rs7903146), PPARG (rs1801282), KCNJ11 (rs5219) and traditional risk factors were studied. Results . Risk alleles of the TCF7L2 gene showed increased risk of diabetes even when controlled for traditional diabetes risk factors (diabetes in family, waist circumference, physical activity, BMI, SBP and total and HDL-cholesterol) in both a cross-sectional and prospective setting (cross-sectional: rs12255372 OR 1.61 (1.31-1.99), rs7903146 OR 1.48 (1.20-1.83) and prospective: rs12255372 OR 1.59 (1.22-2.07), rs7903146 OR 1.47 (1.11-1.93)). The risk alleles of TCF7L2 indicated impaired β-cell function in patients and control subjects. The population attributable risks for diabetes with TCF7L2 risk alleles were 15 % and with diabetes in a first-degree relative 31 %. Conclusion . The risk alleles of the TCF7L2 gene (rs12255372 and rs7903146) were strongly associated with type 2 diabetes, even after controlling for traditional risk factors in both a cross-sectional and prospective setting. These risk alleles were associated with indices of reduced β-cell function. [ABSTRACT FROM AUTHOR]