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Related Concept Videos

Heritability01:06

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Heritability is a statistical concept that measures the degree to which genetic differences among individuals contribute to trait variations within a population. It is a fundamental idea in genetics, often prone to misinterpretation. Heritability is expressed as a percentage, reflecting the proportion of variation in a specific trait across a population that can be linked to genetic differences. However, it's important to understand that heritability does not determine how "genetic"...
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Alzheimer Disease ll: Pathophysiology01:23

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Alzheimer disease involves structural changes in the brain that begin long before symptoms appear. The most distinctive features are extracellular neuritic plaques and intracellular neurofibrillary tangles.Neuritic plaques form in the cerebral cortex and around blood vessels. These plaques contain a dense core of beta-amyloid (Aβ)—a toxic protein fragment that clumps outside neurons. The core is surrounded by damaged neuronal extensions, as well as reactive astrocytes and...
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Alzheimer disease is a chronic, progressive, and irreversible neurodegenerative disorder and the most common cause of dementia in older adults. It leads to gradual neuronal loss, causing cognitive decline, behavioral changes, and loss of functional independence.Risk Factors and EtiologyThe disease is multifactorial. Age is the strongest risk factor, with prevalence doubling every 5 years after age 65. Genetic factors include mutations in genes such as APP, PSEN1, and PSEN2, which are associated...
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Human Genetics01:28

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Human genetics provides a profound framework for understanding the interplay between genetic predispositions and human psychology. At the heart of this discipline lies the study of how genes influence physical traits, behaviors, and susceptibility to diseases. Each person carries a unique genetic code that subtly or significantly shapes their psychological and behavioral landscape.
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Mapping Alzheimer's Disease Variants to Their Target Genes Using Computational Analysis of Chromatin Configuration
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Alzheimer's disease: analyzing the missing heritability.

Perry G Ridge1, Shubhabrata Mukherjee, Paul K Crane

  • 1Department of Biology, Brigham Young University, Provo, Utah, United States of America ; ARUP Institute for Clinical and Experimental Pathology, Salt Lake City, Utah, United States of America.

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|November 19, 2013
PubMed
Summary

Common genetic variations explain 33% of Alzheimer's disease (AD) phenotypic variance, but most of this heritability remains unexplained by known AD markers. Future studies need novel designs to uncover these genetic factors.

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Area of Science:

  • Genetics
  • Neuroscience
  • Complex Trait Analysis

Background:

  • Alzheimer's disease (AD) is a complex neurological disorder with both environmental and genetic influences.
  • Previous research identified 11 AD markers across 10 genetic loci.
  • A significant portion of AD's heritability remains unexplained by currently known genetic factors.

Purpose of the Study:

  • To analyze the phenotypic variance explained by known late-onset AD loci and all common single nucleotide polymorphisms (SNPs) in a large cohort.
  • To identify the proportion of AD heritability attributable to common SNPs.
  • To propose future research strategies for discovering novel AD genetic markers.

Main Methods:

  • Genome-wide Complex Trait Analysis (GCTA) was employed.
  • Analysis included over 2 million SNPs from 10,922 individuals in the Alzheimer's Disease Genetics Consortium (ADGC).
  • Phenotypic variance was assessed by known AD loci and then by all common SNPs.

Main Results:

  • Common SNPs collectively explained 33% of the total phenotypic variance in Alzheimer's disease.
  • The APOE gene alone accounted for 6% of the variance, while other known markers explained 2%.
  • Over 25% of the phenotypic variance is tagged by common SNPs but not explained by known markers.

Conclusions:

  • A substantial portion of Alzheimer's disease heritability is associated with common SNPs not yet linked to specific loci.
  • Novel AD markers contributing significantly to phenotypic variance are likely rare and difficult to detect with current genome-wide association studies.
  • Future research should incorporate specific study designs to identify the remaining heritability of Alzheimer's disease.