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Approach for Genetic Studies

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Precision Medicine in Stroke

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Abstract

The genetic basis of disease started with the recognition of variations of patterns in disease risk and changes in risk among migrants, race/ethnicity, socioeconomic class, time trends, age effects, and gender variation. The first epidemiological steps in dissecting this genetic variation are assessment of family history, twin, and adoption studies at the phenotype level demonstrating that the disease tends to run in families more than would be expected by chance and examination of how that familial tendency is modified by the degree or type of relationship, age, or environmental factors. The next step still on the phenotype level in pedigree data is studies of the families of a population-based series of cases to determine whether the pattern of disease among relatives is compatible with one or more major genes, polygenes, or shared environmental factors. Further assessment is at the genotype level, to collect blood samples from potentially informative members of multiple case families and types of genetic markers at known locations. A variety of strategies exist. Genetic association studies are used to detect association between one or more genetic markers with continuous or discrete phenotype. They allow us to compare different alleles with the phenotype in a similar manner across unrelated individuals or families. Mendelian randomisation uses genetic variants as instrumental variables to infer whether a risk factor causally affects the phenotype. Genome-wide association studies (GWAS) use chip technology to genotype hundreds of thousands of common single-nucleotide polymorphisms (SNPs), which are then analysed for association with a disease or trait. GWAS are hypothesis-free methods for identifying associations between genetic regions and traits. Next-generation sequencing (NGS) is the catch-all term used to describe a number of different modern sequencing technologies. These technologies allow for sequencing of DNA and RNA much more quickly and cheaply than the previously used sequencing, and as such revolutionised the study of genomics and molecular biology. The genetic studies estimate the frequency of the various mutations and the effect of each on disease risk, including any interactions with age, host, or environmental factors.

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Authors and Affiliations

  1. Institute of Cardiovascular Research Royal Holloway, University of London (ICR2UL), London, UK

    Gie Ken-Dror & Pankaj Sharma

  2. Department of Clinical Neuroscience, Imperial College Healthcare NHS Trust, London, UK

    Pankaj Sharma

Authors
  1. Gie Ken-Dror
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  2. Pankaj Sharma
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Correspondence to Pankaj Sharma .

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Editors and Affiliations

  1. Neurology, University of Lisbon, Lisbon, Portugal

    Ana Catarina Fonseca

  2. Department of Neurosciences, University of Lisbon, Lisbon, Portugal

    José M. Ferro

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Ken-Dror, G., Sharma, P. (2021). Approach for Genetic Studies. In: Fonseca, A.C., Ferro, J.M. (eds) Precision Medicine in Stroke. Springer, Cham. https://doi.org/10.1007/978-3-030-70761-3_13

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  • DOI: https://doi.org/10.1007/978-3-030-70761-3_13

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