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By Marta Kobla\u0144ska, January 2, 2026, 15:00 Poland’s time, Photo: double helix of DNA, Pixabay<\/p>\n
The lower the frequency of a disease-inducing gene variant, the larger the absolute effect in size; however, the growth is slower, according to the third most-cited study in 2024, published in Cell Genomics.<\/span><\/span><\/strong><\/p>\n The third most-cited study of 2024, with 101 citations, of which the first authoris is <\/span>Konrad J. Karczewski,<\/strong> originally published in the journal ,,Cell Genomics\u201d <\/strong>\u00a0(Impact Factor 11.1) in September 2022 under the title: ,,<\/span><\/span><\/span>Systematic single-variant and gene-based association testing of thousands of phenotypes in 394,841 UK Biobank exomes”<\/span><\/span><\/span><\/strong> that is<\/span> based on a<\/span>n <\/span>analysis of UK Biobank resources, <\/span>has <\/span>show<\/span>n<\/span> the gene-based<\/span> association between <\/span>about 4500 <\/span>different <\/span>diseases and traits. <\/span><\/span><\/span>However, as the authors point out, a gene considered harmful may have or may gain the potential to alleviate the strong effects that manifest as a disease.<\/span><\/span><\/span><\/span><\/p>\n The <\/span>overall <\/span>\u201cexpression\u201d in phenotype that, in this case (the study purposes), means <\/span>the disease accounts for <\/span>about<\/span> 6<\/span> percent, <\/span>while the number is <\/span>serving up 993,280,477 gene-level association statistics <\/span><\/span>(across <\/span>protein-coding <\/span>19,407 genes, up to 4 functional annotation sets, and 3 burden tests) <\/span>and 28,158,190,538 single-variant association statistics across 8,074,878 exome variants. <\/span><\/span>These statistics included a dataset of nearly 400,000 individuals of European ancestry <\/span><\/span>and relatives, <\/span><\/span>and 451,000 in total. To make an image of the study’s importance and a painted picture of Europeans’ health status<\/strong>, the authors note, that the four annotation categories comprise the,, <\/span><\/span><\/span><\/span>predicted LoF (pLoF- the gene’s tolerance for function loss), missense (including low-confidence pLoF variants and in-frame insertions or deletions [indels]), synonymous, and the combination pLoF or missense group, resulting in the mentioned 8,074,878 variants and 75,767 groups for association testing.\u00a0<\/span><\/span><\/span><\/span><\/p>\n T<\/span><\/span>he main conclusion of the paper is that we may be genetically vulnerable\/predisposed to a disease, which is influenced by natural selection (negative in the case of the most severe<\/span><\/span>\u00a0<\/span><\/span>manifestations). – However, the process of the negative selection <\/strong><\/em><\/span><\/span>will tend to decrease the frequency of functionally damaging variants, suggesting that variants with large effect sizes are more likely to be rare, <\/span><\/span><\/em>according to scientists<\/span><\/span>.<\/span><\/span><\/strong><\/span><\/span><\/p>\n Some interpretations of the study suggest that evolution has established its own security checkpoints. In simpler terms, we may accept a slightly lower overall health status among a larger population to allow for the survival of individuals with rare but more severe illnesses.<\/span><\/p>\n In line with the study, the phenotype, thus the expression of diseases in the case of the single-gen variant, will be mainly shown in endocrinometabolic, digestive, skin\/subcutaneous, and musculoskeletal malformations, as well as circulatory, nervous, and eye problems. <\/span><\/span>The good news is that neoplasms, which <\/span><\/span>can <\/span><\/span>lead to cancer, tend to stabilize. <\/span><\/span><\/strong> Nonetheless, the <\/span><\/span>outcomes of health problems <\/span><\/span>that <\/span><\/span>originate from a certain impairment due to genes\u2019 mixture can be similar to those revealed for single-gene variance.<\/span><\/span><\/span><\/span><\/p>\n What does this mean? There may be additional associations between certain numbers and diseases or developmental delays; however, these associations are not expected to alter the genetic information that we all carry.<\/strong> This allows the genes inhibiting health burdens to continue functioning. Although scientists have observed a correlation with key genes that are considered the most significant, they indicate that these genes are more likely to be associated with a phenotype (6.38%) compared to a frequency-matched set of genes. That reversed association (a correlation between selection against the tolerance of a gene function loss, which may be high or low) means that even if we are carrying a harmful gene, it does not need to be expressed\/doesn’t need to impact the gene’s structure\/ morphology\/physiology, or behaviour\/performance.\u00a0<\/span><\/p>\n <\/p>\n <\/p>\n \n","protected":false},"excerpt":{"rendered":" By Marta Kobla\u0144ska, January 2, 2026, 15:00 Poland’s time, Photo: double helix of DNA, Pixabay The lower the frequency of a disease-inducing gene variant, the larger the absolute effect in size; however, the growth is slower, according to the third most-cited study in 2024, published in Cell Genomics. The third most-cited study of 2024, with […]<\/p>\n","protected":false},"author":1,"featured_media":0,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"advanced_seo_description":"","jetpack_seo_html_title":"","jetpack_seo_noindex":false,"_jetpack_memberships_contains_paid_content":false,"footnotes":""},"categories":[5,4,10,1,6],"tags":[],"class_list":["post-1723","post","type-post","status-publish","format-standard","hentry","category-evolution-in-a-nutshell","category-genetics","category-health-security-in-a-nutshell","category-healthmedical-security","category-medicine-in-a-nutshell"],"jetpack_featured_media_url":"","jetpack_sharing_enabled":true,"_links":{"self":[{"href":"https:\/\/evolutionandsecurity.com\/index.php?rest_route=\/wp\/v2\/posts\/1723","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/evolutionandsecurity.com\/index.php?rest_route=\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/evolutionandsecurity.com\/index.php?rest_route=\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/evolutionandsecurity.com\/index.php?rest_route=\/wp\/v2\/users\/1"}],"replies":[{"embeddable":true,"href":"https:\/\/evolutionandsecurity.com\/index.php?rest_route=%2Fwp%2Fv2%2Fcomments&post=1723"}],"version-history":[{"count":20,"href":"https:\/\/evolutionandsecurity.com\/index.php?rest_route=\/wp\/v2\/posts\/1723\/revisions"}],"predecessor-version":[{"id":1820,"href":"https:\/\/evolutionandsecurity.com\/index.php?rest_route=\/wp\/v2\/posts\/1723\/revisions\/1820"}],"wp:attachment":[{"href":"https:\/\/evolutionandsecurity.com\/index.php?rest_route=%2Fwp%2Fv2%2Fmedia&parent=1723"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/evolutionandsecurity.com\/index.php?rest_route=%2Fwp%2Fv2%2Fcategories&post=1723"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/evolutionandsecurity.com\/index.php?rest_route=%2Fwp%2Fv2%2Ftags&post=1723"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}