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Next Generation Rare Variant Discovery in Multiplex AD Families

Next Generation Rare Variant Discovery in Multiplex AD Families
多重 AD 家族中下一代罕见变异的发现
批准号:
10214751
负责人:
David B. Goldstein
金额:
$15.63万
依托单位国家:
美国
项目类别:
财政年份:
2015
资助国家:
美国
项目状态:
已结题
起止时间:
2015-09-01 至 2022-05-31

项目摘要

项目成果

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中文摘要
翻译
世界卫生组织(世卫组织)目前报告了4 793 076例确诊病例
英文摘要
The World Health Organization (WHO) is currently reporting 4,793,076 confirmed cases of COVID-19 infection world-wide with 316,341 deaths. With each new pandemic the population is at risk until vaccines and medications can be developed. Quarantine of the entire population appears to be only alternative until sufficient time elapses for vaccine development. Therefore, an important public health goal is to determine who must be sheltered in place and who can resume normal activities. Older individuals appear to be disproportionately adversely affected by the virus. Although immune functioning tends to wane with age, genetic and lifestyle factors appear to greatly alter susceptibility. The goal of this project is to identify individuals who may be more or less resilient due to their lifetime use of alcohol. Those with an alcohol use disorder (AUD) may have a greater risk for adverse consequences of SARS-CoV-2 exposure, yet low dose consumption may improve immune functioning. A better understanding of whether alcohol use has a different effect at low doses than at high doses is critical to public health campaigns that advise the public on safe use of alcohol. Genetic variation in the Major Histocompatiblity Locus (MHC) located on chromosome 6 plays an important role in immune functioning. Variation in the human leucocyte antigens (HLA) have been significantly associated with many diseases and hold promise for personalized antigen-specific disease prevention. Having this information available, as part of routine medical screening in the future, would enable us to stratify the population into those needing sheltering in place and those who do not. This project would determine the feasibility of using HLA gene variation along with screening for alcohol use as an important part of stratifying the population at the onset of viral epidemics. The present proposal builds on existing resources from participants for whom exome sequencing and/or HLA serology was completed and utilizes the extensive alcohol use histories, psychiatric diagnoses, and health histories obtained at baseline. New interviews concerning alcohol use, both distal and proximal, current health status, and exposure histories for the SARS- CoV-2 virus will enable us to determine their contribution to infection and progression. We will contrast those with AUD with those without and unaffected members of high risk versus low risk families in (Aim 1). In Aim 2, we will assess levels of recent and past alcohol consumption to viral response. Genetic variation in the major histocompatibility complex (HLA) region will be tested for association with outcome among those that are demonstrated to have been exposed (Aim 3).
期刊论文(1)
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会议论文
Factors influencing COVID-19 Infection in older individuals: History of Alcohol Use Disorder, Major Depressive illness, genetic variation and current use of alcohol.
影响老年人感染 COVID-19 的因素:酒精使用障碍史、重度抑郁症、遗传变异和当前饮酒情况。
DOI: 10.1101/2021.12.06.21267386
发表时间: 2021
期刊: medRxiv : the preprint server for health sciences
影响因子: --
作者: [Hill,ShirleyY, Holmes,BrianJ, Locke-Wellman,Jeannette]
通讯作者: Locke-Wellman,Jeannette
Next Generation Rare Variant Discovery in Multiplex AD Families
Next Generation Rare Variant Discovery in Multiplex AD Families
1/3-Identifying regulatory mutations that influence neuropsychiatric disease
  • 批准号:
    8805881
  • 项目类别:
  • 资助金额:
    $12.06万
  • 财政年份:
    2014
  • 负责人:
    David B. Goldstein
  • 依托单位:
An integrated and diverse genomic medicine program for undiagnosed diseases
  • 批准号:
    9081624
  • 项目类别:
  • 资助金额:
    $230.0万
  • 财政年份:
    2014
  • 负责人:
    David B. Goldstein
  • 依托单位:
海外基金