Why does a person get sick?
The answer is 110 million case histories long
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A group of scientists from Chicago has done a truly titanic job. They processed 110 million case histories in search of a link between monogenic diseases caused by known mutations and diseases whose exact causes are unknown (Blair et al., A Nondegenerate Code of Deleterious Variants in Mendelian Loci Contributes to Complex Disease Risk // Cell, 2013).
Why does a person get sick? Some diseases are caused by pathogens coming from outside: bacteria, viruses or some other parasites. Sometimes diseases are caused genetically. For a number of diseases, an unambiguous relationship between the disease and a mutation in the genome has been revealed. For example, for cystic fibrosis, sickle cell anemia, Down's disease, hemophilia. For some other diseases, such a connection may exist, but be less rigid. Then they talk about hereditary predisposition. This is the case, for example, with inherited breast cancer. Some mutations significantly increase the risk of getting sick, but not all, and yet rarely up to 100%. In some cases, family histories suggest that the role of heredity in the development of the disease is great, but it is not possible to detect specific genes responsible for the disease. This happens with cardiovascular diseases, diabetes, and some mental illnesses. In such cases, one should not forget about the influence of the environment and, in particular, lifestyle. If we add to this the fact that mutations can not only be inherited from parents, but also appear in humans for the first time, it becomes clear how difficult it is to identify the causes of diseases.
Today, it is impossible to say unequivocally about most of the diseases most relevant for developed countries (cardiovascular, oncological, diabetes mellitus), whether they are genetically determined, and, if so, how much, and which genes. Since it is very important to find out, many large-scale studies are being conducted, candidate genes are being found, assumptions are being made about the mechanism of their influence, in short, work is in full swing. Understanding the exact mechanisms of the disease will greatly simplify treatment, help to create fundamentally new drugs, and, possibly, gene therapy approaches to treatment.
The calculation of researchers who studied 110 million case histories of patients from the USA and Denmark was as follows: if there is a noticeable positive correlation between a monogenic disease and a disease of unknown nature, then it will be possible to suggest that the same genes that are responsible for a monogenic disease are responsible for another.
It turned out that almost every multifactorial disease can be matched with a unique set of monogenic diseases and, accordingly, genetic loci. In total, about 3000 correlations were found. Some of them are already well-known. For example, problems of lipid metabolism were associated with the risk of heart attacks and heart failure. Others were much more unexpected. Thus, Morphan syndrome (connective tissue disease) was associated with neuropsychiatric diseases: autism, manic-depressive psychosis and depression. The syndrome of the brittle X chromosome (characterized mainly by mental retardation) has been associated with asthma, psoriasis and a tendency to viral infections, so perhaps the immune system is somehow affected here.
The authors have mapped the genes of monogenic diseases that have a high correlation with multifactorial diseases.
Graph from the article in Cell – VM.Now they propose to look in the vicinity of these genes for less destructive mutations that do not cause monogenic diseases, but increase the likelihood of multifactorial ones.
Portal "Eternal youth" http://vechnayamolodost.ru02.10.2013