Concordance (genetics)

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In genetics, concordance is the probability that a pair of individuals will both have a certain characteristic (phenotypic trait) given that one of the pair has the characteristic. Concordance can be measured with concordance rates, reflecting the odds of one person having the trait if the other does. Important clinical examples include the chance of offspring having a certain disease if the mother has it, if the father has it, or if both parents have it. Concordance among siblings is similarly of interest: what are the odds of a subsequent offspring having the disease if an older child does? In research, concordance is often discussed in the context of both members of a pair of twins. Twins are concordant when both have or both lack a given trait. [1] The ideal example of concordance is that of identical twins, because the genome is the same, an equivalence that helps in discovering causation via deconfounding, regarding genetic effects versus epigenetic and environmental effects (nature versus nurture).

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In contrast, discordance occurs when a similar trait is not shared by the persons. Studies of twins have shown that genetic traits of monozygotic twins are fully concordant, whereas in dizygotic twins, half of genetic traits are concordant, while the other half are discordant. Discordant rates that are higher than concordant rates express the influence of the environment on twin traits. [2]

Studies

A twin study compares the concordance rate of identical twins to that of fraternal twins. This can help suggest whether a disease or a certain trait has a genetic cause. [3] Controversial uses of twin data have looked at concordance rates for homosexuality and intelligence. Other studies have involved looking at the genetic and environmental factors that can lead to increased LDL in women twins. [4]

Because identical twins are genetically virtually identical, it follows that a genetic pattern carried by one would very likely also be carried by the other. If a characteristic identified in one twin is caused by a certain gene, then it would also very likely be present in the other twin. Thus, the concordance rate of a given characteristic helps suggest whether or to what extent a characteristic is related to genetics.

There are several problems with this assumption:

  1. A given genetic pattern may not have 100% penetrance, in which case it may have different phenotypic consequences in genetically identical individuals;
  2. Developmental and environmental conditions may be different for genetically identical individuals. If developmental and environmental conditions contribute to the development of the disease or other characteristic, there can be differences in the outcome of genetically identical individuals;
  3. The logic is further complicated if the characteristic is polygenic, i.e., caused by differences in more than one gene.
  4. Epigenetic effects can alter the genetic expressions in twins through varied factors. The expression of the epigenetic effect is typically weakest when the twins are young and increases as the identical twins grow older. [5]
  5. Where in the absence of one or more environmental factors a condition will not develop in an individual, even with high concordance rates, the proximate cause is environmental, with strong genetic influence: thus "a substantial role of genetic factors does not preclude the possibility that the development of the disease can be modified by environmental intervention." So "genetic factors are assumed to contribute to the development of that disease", but cannot be assumed alone to be causal. [6]

Genotyping studies

In genotyping studies where DNA is directly assayed for positions of variance (see SNP), concordance is a measure of the percentage of SNPs that are measured as identical. Samples from the same individual or identical twins theoretically have a concordance of 100%, but due to assaying errors and somatic mutations, they are usually found in the range of 99% to 99.95%. Concordance can therefore be used as a method of assessing the accuracy of a genotyping assay platform.

Because a child inherits half of his or her DNA from each parent, parents and children, siblings, and fraternal (dizygotic) twins have a concordance that averages 50% using this measure.

See also

Related Research Articles

An allele, or allelomorph, is a variant of the sequence of nucleotides at a particular location, or locus, on a DNA molecule.

The genotype of an organism is its complete set of genetic material. Genotype can also be used to refer to the alleles or variants an individual carries in a particular gene or genetic location. The number of alleles an individual can have in a specific gene depends on the number of copies of each chromosome found in that species, also referred to as ploidy. In diploid species like humans, two full sets of chromosomes are present, meaning each individual has two alleles for any given gene. If both alleles are the same, the genotype is referred to as homozygous. If the alleles are different, the genotype is referred to as heterozygous.

Nature versus nurture is a long-standing debate in biology and society about the relative influence on human beings of their genetic inheritance (nature) and the environmental conditions of their development (nurture). The alliterative expression "nature and nurture" in English has been in use since at least the Elizabethan period and goes back to medieval French. The complementary combination of the two concepts is an ancient concept. Nature is what people think of as pre-wiring and is influenced by genetic inheritance and other biological factors. Nurture is generally taken as the influence of external factors after conception e.g. the product of exposure, experience and learning on an individual.

<span class="mw-page-title-main">Genotype–phenotype distinction</span> Distinction made in genetics

The genotype–phenotype distinction is drawn in genetics. "Genotype" is an organism's full hereditary information. "Phenotype" is an organism's actual observed properties, such as morphology, development, or behavior, and the consequences thereof. This distinction is fundamental in the study of inheritance of traits and their evolution.

<span class="mw-page-title-main">Twin</span> One of two offspring produced by the same pregnancy

Twins are two offspring produced by the same pregnancy. Twins can be either monozygotic ('identical'), meaning that they develop from one zygote, which splits and forms two embryos, or dizygotic, meaning that each twin develops from a separate egg and each egg is fertilized by its own sperm cell. Since identical twins develop from one zygote, they will share the same sex, while fraternal twins may or may not. In very rare cases twins can have the same mother and different fathers.

<span class="mw-page-title-main">Heritability</span> Estimation of effect of genetic variation on phenotypic variation of a trait

Heritability is a statistic used in the fields of breeding and genetics that estimates the degree of variation in a phenotypic trait in a population that is due to genetic variation between individuals in that population. The concept of heritability can be expressed in the form of the following question: "What is the proportion of the variation in a given trait within a population that is not explained by the environment or random chance?"

Twin studies are studies conducted on identical or fraternal twins. They aim to reveal the importance of environmental and genetic influences for traits, phenotypes, and disorders. Twin research is considered a key tool in behavioral genetics and in related fields, from biology to psychology. Twin studies are part of the broader methodology used in behavior genetics, which uses all data that are genetically informative – siblings studies, adoption studies, pedigree, etc. These studies have been used to track traits ranging from personal behavior to the presentation of severe mental illnesses such as schizophrenia.

<span class="mw-page-title-main">Human variability</span> Range of possible values for any characteristic of human beings

Human variability, or human variation, is the range of possible values for any characteristic, physical or mental, of human beings.

A quantitative trait locus (QTL) is a locus that correlates with variation of a quantitative trait in the phenotype of a population of organisms. QTLs are mapped by identifying which molecular markers correlate with an observed trait. This is often an early step in identifying the actual genes that cause the trait variation.

<span class="mw-page-title-main">Human behaviour genetics</span> Field that examines the role of genetic and environmental influences on human behaviour

Human behaviour genetics is an interdisciplinary subfield of behaviour genetics that studies the role of genetic and environmental influences on human behaviour. Classically, human behavioural geneticists have studied the inheritance of behavioural traits. The field was originally focused on determining the importance of genetic influences on human behaviour. It has evolved to address more complex questions such as: how important are genetic and/or environmental influences on various human behavioural traits; to what extent do the same genetic and/or environmental influences impact the overlap between human behavioural traits; how do genetic and/or environmental influences on behaviour change across development; and what environmental factors moderate the importance of genetic effects on human behaviour. The field is interdisciplinary, and draws from genetics, psychology, and statistics. Most recently, the field has moved into the area of statistical genetics, with many behavioural geneticists also involved in efforts to identify the specific genes involved in human behaviour, and to understand how the effects associated with these genes changes across time, and in conjunction with the environment.

In genetics, expressivity is the degree to which a phenotype is expressed by individuals having a particular genotype. Alternatively, it may refer to the expression of a particular gene by individuals having a certain phenotype. Expressivity is related to the intensity of a given phenotype; it differs from penetrance, which refers to the proportion of individuals with a particular genotype that share the same phenotype.

A genetic predisposition is a genetic characteristic which influences the possible phenotypic development of an individual organism within a species or population under the influence of environmental conditions. In medicine, genetic susceptibility to a disease refers to a genetic predisposition to a health problem, which may eventually be triggered by particular environmental or lifestyle factors, such as tobacco smoking or diet. Genetic testing is able to identify individuals who are genetically predisposed to certain diseases.

<span class="mw-page-title-main">Gene–environment interaction</span> Response to the same environmental variation differently by different genotypes

Gene–environment interaction is when two different genotypes respond to environmental variation in different ways. A norm of reaction is a graph that shows the relationship between genes and environmental factors when phenotypic differences are continuous. They can help illustrate GxE interactions. When the norm of reaction is not parallel, as shown in the figure below, there is a gene by environment interaction. This indicates that each genotype responds to environmental variation in a different way. Environmental variation can be physical, chemical, biological, behavior patterns or life events.

<span class="mw-page-title-main">Heritability of autism</span>

The heritability of autism is the proportion of differences in expression of autism that can be explained by genetic variation; if the heritability of a condition is high, then the condition is considered to be primarily genetic. Autism has a strong genetic basis. Although the genetics of autism are complex, autism spectrum disorder (ASD) is explained more by multigene effects than by rare mutations with large effects.

Behavioural genetics, also referred to as behaviour genetics, is a field of scientific research that uses genetic methods to investigate the nature and origins of individual differences in behaviour. While the name "behavioural genetics" connotes a focus on genetic influences, the field broadly investigates the extent to which genetic and environmental factors influence individual differences, and the development of research designs that can remove the confounding of genes and environment. Behavioural genetics was founded as a scientific discipline by Francis Galton in the late 19th century, only to be discredited through association with eugenics movements before and during World War II. In the latter half of the 20th century, the field saw renewed prominence with research on inheritance of behaviour and mental illness in humans, as well as research on genetically informative model organisms through selective breeding and crosses. In the late 20th and early 21st centuries, technological advances in molecular genetics made it possible to measure and modify the genome directly. This led to major advances in model organism research and in human studies, leading to new scientific discoveries.

A twin registry is a database of information about both identical twins and fraternal twins, which is often maintained by an academic institution, such as a university, or by other research institutions.

Genome-wide complex trait analysis (GCTA) Genome-based restricted maximum likelihood (GREML) is a statistical method for heritability estimation in genetics, which quantifies the total additive contribution of a set of genetic variants to a trait. GCTA is typically applied to common single nucleotide polymorphisms (SNPs) on a genotyping array and thus termed "chip" or "SNP" heritability.

Epigenetics in forensic science is the application of epigenetics to solving crimes.

Personality traits are patterns of thoughts, feelings and behaviors that reflect the tendency to respond in certain ways under certain circumstances.

Multifactorial diseases are not confined to any specific pattern of single gene inheritance and are likely to be caused when multiple genes come together along with the effects of environmental factors.

References

  1. ↑ Lewontin R (March 1982). Human diversity. Scientific American Press. ISBN   978-0-7167-1469-9.
  2. ↑ "Concordant vs Discordant – Twin Studies – Meddiction" . Retrieved 2020-06-19.
  3. ↑ van den Berg SM, Hjelmborg JV (September 2012). "Genetic analysis of rare disorders: bayesian estimation of twin concordance rates". Behavior Genetics. 42 (5): 857–65. doi:10.1007/s10519-012-9547-9. PMC   3442174 . PMID   22711379.
  4. ↑ Austin MA, Newman B, Selby JV, Edwards K, Mayer EJ, Krauss RM (May 1993). "Genetics of LDL subclass phenotypes in women twins. Concordance, heritability, and commingling analysis". Arteriosclerosis and Thrombosis. 13 (5): 687–95. doi: 10.1161/01.ATV.13.5.687 . PMID   8485120.
  5. ↑ "Inherent similarities in identical twins may not be so strong (Identical twins may be more different f...)". Bio-Medicine. Archived from the original on 2017-08-09. Retrieved 2010-06-27.
  6. ↑ Thomsen SF, Stensballe LG, Skytthe A, Kyvik KO, Backer V, Bisgaard H (March 2008). "Increased concordance of severe respiratory syncytial virus infection in identical twins". Pediatrics. 121 (3): 493–6. doi:10.1542/peds.2007-1889. PMID   18310197. S2CID   5192096.
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