RESUMO
With the advent of whole genome-sequencing (WGS) studies, family-based designs enable sex-specific analysis approaches that can be applied to only affected individuals; tests using family-based designs are attractive because they are completely robust against the effects of population substructure. These advantages make family-based association tests (FBATs) that use siblings as well as parents especially suited for the analysis of late-onset diseases such as Alzheimer's Disease (AD). However, the application of FBATs to assess sex-specific effects can require additional filtering steps, as sensitivity to sequencing errors is amplified in this type of analysis. Here, we illustrate the implementation of robust analysis approaches and additional filtering steps that can minimize the chances of false positive-findings due to sex-specific sequencing errors. We apply this approach to two family-based AD datasets and identify four novel loci (GRID1, RIOK3, MCPH1, ZBTB7C) showing sex-specific association with AD risk. Following stringent quality control filtering, the strongest candidate is ZBTB7C (Pinter = 1.83 × 10-7), in which the minor allele of rs1944572 confers increased risk for AD in females and protection in males. ZBTB7C encodes the Zinc Finger and BTB Domain Containing 7C, a transcriptional repressor of membrane metalloproteases (MMP). Members of this MMP family were implicated in AD neuropathology.
Assuntos
Doença de Alzheimer/genética , Análise de Dados , Bases de Dados Genéticas , Família , Estudos de Associação Genética , Loci Gênicos/genética , Estudo de Associação Genômica Ampla , Peptídeos e Proteínas de Sinalização Intracelular/genética , Sequenciamento Completo do Genoma , Alelos , Domínio BTB-POZ/genética , Feminino , Humanos , Masculino , Metaloproteases/genética , Metaloproteases/metabolismo , Risco , Fatores Sexuais , Dedos de Zinco/genéticaRESUMO
Dental implants as abutments for full-arch restorations are a well-documented treatment modality. This report presents a case in which the patient was treated initially with fixed restorations supported by either implants or natural teeth and subsequently treated with a removable implant/telescopic crown-supported overdenture. Advantages and disadvantages of each approach are described and discussed. While the fixed restoration resulted in a functionally satisfactory treatment outcome, the patient was displeased with the esthetic appearance. The main concern was the unnaturally long tooth shape necessary to compensate for the insufficient alveolar ridge height. Replacement of the existing restoration with an implant-supported removable overdenture led to a functionally and esthetically acceptable result. When deciding whether to use a fixed or removable implant-supported full-arch restoration, a multitude of factors must be considered. Due to the possible need for additional surgical steps to enhance the esthetic appearance surrounding fixed restorations, removable implant-supported partial dentures often are the better choice.