Study Of Susceptibility Genes Research Articles

A study of susceptibility genes in rare monozygotic twins with generalized aggressive periodontitis

A study of susceptibility genes in rare monozygotic twins with generalized aggressive periodontitis

Association of IL17RC and COL6A1 genetic polymorphisms with susceptibility to ossification of the thoracic posterior longitudinal ligament in Chinese patients

BackgroundIn our previous whole-genome sequencing study of 30 unrelated northern Chinese Han patients, we identified six single nucleotide polymorphisms (SNPs) in the interleukin 17 receptor C (IL17RC) and collagen type VI α1 chain (COL6A1) genes that were potentially associated with thoracic ossification of the posterior longitudinal ligament (T-OPLL). To determine whether these six SNPs are associated with susceptibility to T-OPLL in the northern Chinese Han population, we performed a case-control association study to confirm specific susceptible loci in the expanded samples.MethodsThe six SNPs in the IL17RC and COL6A1 genes were analyzed in 200 northern Chinese individuals (100 patients and 100 control subjects) using the Sequenom system.ResultsThe genotype distributions and allele frequencies of each SNP in the control and patient groups were compared. rs201153092, rs13051496, rs199772854, rs76999397, and rs189013166 showed potential pathogenic loci for T-OPLL in the northern Chinese Han population, whereas rs151158105 did not. At the genotype level, the differences in the genotype frequencies of rs201153092, rs13051496, rs199772854, rs76999397, and rs189013166 between T-OPLL cases and controls reached statistical significance.ConclusionsTo the best of our knowledge, this is the first association study of susceptibility genes in Han Chinese patients with T-OPLL. The results revealed five SNPs in the IL17RC and COL6A1 genes that represented potentially pathogenic mutations in patients with T-OPLL.

Abstract MP59: Revisiting Heritability Accounting For Common Environmental Effects And Maternal Inheritance

Background: Heritability measures the proportion of phenotypic variation attributable to genetic factors. Reliable heritability estimates are used to determine the necessary sample size and power for subsequent genetic studies of susceptibility genes. In addition to a shared nuclear genetic component, common environmental factors and maternal or mitochondrial inheritance may have strong effects on some phenotypes. Failure to account for necessary variance components may give rise to biased heritability estimates. Aims: Our primary goal was to investigate how heritability estimates are biased in the presence of common environmental or/and maternal effects. The second goal was to estimate mitochondrial inheritance for a number of common phenotypes. Methods: We employed variance component methods to account for additional variance components using both simulated and Framingham Heart Study (FHS) pedigree data to revisit heritability estimates in the presence of common environmental and maternal effects. Results: Using both simulated families and actual FHS extended pedigrees, we demonstrated that heritability is greatly overestimated when key variance components are not properly accounted for. The inflation in heritability ranged from 9% to 214% across several anthropometric, metabolic and life-style phenotypes when we compared models that consider correct variance components and simple models that only consider familial relationships (Table 1). Maternal inheritance was observed in most phenotypes investigated. The estimated maternal inheritance ranged from ~1 to 5%, which is considerable because the mitochondrial genome is about the size of an average gene. Conclusion/Discussion: We systematically investigated the influence of common environmental effects and maternal inheritance in heritability estimates using extended pedigrees. Our findings may explain, in part, the missing heritability for some traits and may facilitate further collaborations in the genetic study of mitochondrial DNA in disease susceptibility for common phenotypes.

Reliability of Self-reported Ancestry among Siblings: Implications for Genetic Association Studies

This study investigated the reliability of self-reported ancestry by comparing the interview responses of probands and their siblings. A total of 546 sibling pairs were ascertained in a family-based study of susceptibility genes for Parkinson's disease and asked to identify maternal and paternal countries of origin. Probands were recruited prospectively from the Department of Neurology of the Mayo Clinic in Rochester, Minnesota, from June 1, 1996, through May 31, 2005. Probands resided within Minnesota or one of the four surrounding states (Wisconsin, Iowa, South Dakota, North Dakota). Only 49 percent of these sibling pairs, primarily Caucasian, agreed completely on the countries of origin of both parents. The agreement increased to 68 percent when named countries were postcoded into six population genetic clusters (as previously defined by microsatellite markers). Self-reported ancestry may not be a reliable method to reduce the possible impact of population stratification in genetic association studies of outbred populations, such as in the United States.