{"id":3413,"date":"2019-04-24T11:19:47","date_gmt":"2019-04-24T02:19:47","guid":{"rendered":"http:\/\/163.180.4.222\/lab\/?p=3413"},"modified":"2019-04-24T11:19:47","modified_gmt":"2019-04-24T02:19:47","slug":"genetic-study-homes-in-on-heights-heritability-mystery","status":"publish","type":"post","link":"https:\/\/biochemistry.khu.ac.kr\/lab\/?p=3413","title":{"rendered":"Genetic study homes in on height\u2019s heritability mystery"},"content":{"rendered":"<p>&nbsp;<\/p>\n<p>&nbsp;<\/p>\n<h5>Analysis of 20,000 genomes reveals that rare gene variants can help to explain how the trait is inherited.<\/h5>\n<p>&nbsp;<\/p>\n<div class=\"article__body serif cleared\">\n<figure class=\"figure\">\n<div class=\"embed intensity--high\">\n<div class=\"embed intensity--high\"><img decoding=\"async\" class=\"figure__image\" src=\"https:\/\/media.nature.com\/w800\/magazine-assets\/d41586-019-01157-y\/d41586-019-01157-y_16646786.jpg\" alt=\"Silhouetted people of various heights walk across London Bridge at sunset.\" data-src=\"\/\/media.nature.com\/w800\/magazine-assets\/d41586-019-01157-y\/d41586-019-01157-y_16646786.jpg\" \/><\/div>\n<\/div><figcaption>\n<p class=\"figure__caption sans-serif\"><span class=\"mr10\">Height is often inherited \u2014 but the precise genetics factors have long eluded researchers.<\/span>Credit: Shomos Uddin\/Getty<\/p>\n<\/figcaption><\/figure>\n<p>&nbsp;<\/p>\n<p>&nbsp;<\/p>\n<p>You need only to look at families to see that\u00a0<a href=\"https:\/\/www.nature.com\/news\/2007\/070902\/full\/news070827-8.html\" data-track=\"click\" data-label=\"https:\/\/www.nature.com\/news\/2007\/070902\/full\/news070827-8.html\" data-track-category=\"body text link\">height is inherited<\/a>\u00a0\u2014 and studies of identical twins and families have long confirmed that suspicion. About 80% of variation in height is down to genetics, they suggest. But since the\u00a0<a href=\"https:\/\/www.nature.com\/news\/human-genome-project-twenty-five-years-of-big-biology-1.18436\" data-track=\"click\" data-label=\"https:\/\/www.nature.com\/news\/human-genome-project-twenty-five-years-of-big-biology-1.18436\" data-track-category=\"body text link\">human genome was sequenced nearly two decades ago<\/a>, researchers have struggled to fully identify the genetic factors responsible.<\/p>\n<p>Studies seeking the genes that govern height have identified hundreds of common gene variants linked to the trait. But the findings also posed a quandry: each variant had a tiny effect on height that together didn\u2019t amount to the genetic contribution predicted by family studies. This phenomenon, which occurs for many other traits and diseases,\u00a0<a href=\"https:\/\/www.nature.com\/news\/2008\/081105\/full\/456018a.html\" data-track=\"click\" data-label=\"https:\/\/www.nature.com\/news\/2008\/081105\/full\/456018a.html\" data-track-category=\"body text link\">was dubbed missing heritability<\/a>, and had even prompted some researchers to speculate that there\u2019s something fundamentally wrong with our understanding of genetics.<\/p>\n<p>&nbsp;<\/p>\n<aside class=\"recommended pull pull--left sans-serif\" data-label=\"Related\"><a href=\"https:\/\/www.nature.com\/news\/2008\/081105\/full\/456018a.html\" data-track=\"click\" data-track-label=\"recommended article\"><img decoding=\"async\" class=\"recommended__image\" src=\"https:\/\/media.nature.com\/w400\/magazine-assets\/d41586-019-01157-y\/d41586-019-01157-y_16179380.jpg\" \/><\/a><\/p>\n<p class=\"recommended__title serif\">The case of the missing heritability<\/p>\n<\/aside>\n<p>&nbsp;<\/p>\n<p>&nbsp;<\/p>\n<p>Now, a study suggests that most of the missing heritability for height and body mass index (BMI) can, as some researchers had suspected, be found in rarer gene variants that had lain undiscovered until now.<\/p>\n<p>\u201cIt is a reassuring paper because it suggests that there isn\u2019t something terribly wrong with genetics,\u201d says Tim Spector, a genetic epidemiologist at King\u2019s College London. \u201cIt\u2019s just that sorting it out is more complex than we thought.\u201d The\u00a0<a href=\"https:\/\/www.biorxiv.org\/content\/10.1101\/588020v1\" data-track=\"click\" data-label=\"https:\/\/www.biorxiv.org\/content\/10.1101\/588020v1\" data-track-category=\"body text link\">research<\/a>\u00a0was posted<sup><a href=\"https:\/\/www.nature.com\/articles\/d41586-019-01157-y?utm_source=feedburner&amp;utm_medium=feed&amp;utm_campaign=Feed%3A+nature%2Frss%2Fcurrent+%28Nature+-+Issue%29#ref-CR1\">1<\/a><\/sup>\u00a0to the bioRxiv preprint server on 25 March.<\/p>\n<p>&nbsp;<\/p>\n<p><strong>Scouring the genome<\/strong><\/p>\n<p>To seek out the genetic factors that underlie diseases and traits, geneticists turn to\u00a0<a href=\"https:\/\/www.nature.com\/news\/new-concerns-raised-over-value-of-genome-wide-disease-studies-1.22152\" data-track=\"click\" data-label=\"https:\/\/www.nature.com\/news\/new-concerns-raised-over-value-of-genome-wide-disease-studies-1.22152\" data-track-category=\"body text link\">mega-searches known as genome-wide association studies (GWAS)<\/a>. These scour the genomes of, typically, tens of thousands of people \u2014 or, increasingly, more than a million \u2014 for single-letter changes, or SNPs, in genes that commonly appear in individuals with a particular disease or that could explain a common trait such as height.<\/p>\n<p>But GWAS have limitations. Because sequencing the entire genomes of thousands of people is expensive, GWAS themselves scan only a strategically selected set of SNPs, perhaps 500,000, in each person\u2019s genome. That\u2019s only a snapshot of the roughly six billion nucleotides \u2014 the building blocks of DNA \u2014 strung together in our genome. In turn, these 500,000 common variants would have been found from sequencing the genomes of just a few hundred people, says Timothy Frayling, a human geneticist at the University of Exeter, UK.<\/p>\n<p>A team led by Peter Visscher at the Queensland Brain Institute in Brisbane, Australia, decided to investigate whether rarer SNPs than those typically scanned in GWAS might explain the missing heritability for height and BMI. They turned to whole-genome sequencing \u2014 performing a complete readout of all 6 billion bases \u2014 of 21,620 people. (The authors declined to comment on the preprint, because it is under submission at a journal.)<\/p>\n<p>They relied on the simple, but powerful, principle that all people are related to some extent \u2014 albeit distantly \u2014 and that DNA can be used to calculate degrees of relatedness. Then, information on the people\u2019s height and BMI could be combined to identify both common and rare SNPs that might be contributing to these traits.<\/p>\n<p>Say, for instance, that a pair of third cousins is closer in height than a pair of second cousins is in a different family: that\u2019s an indication that the third cousins\u2019 height is mostly down to genetics, and the extent of that correlation will tell you how much, Frayling explains. \u201cThey used all of the genetic information, which enables you to work out how much of the relatedness was due to rarer things as well as the common things.\u201d<\/p>\n<p>As a result, the researchers captured genetic differences that occur in only 1 in 500, or even 1 in 5,000, people.<\/p>\n<p>And by using information on both common and rare variants, the researchers arrived at roughly the same estimates of heritability as those indicated by twin studies. For height, Visscher and colleagues estimate a heritability of 79%, and for BMI, 40%. This means that if you take a large group of people, 79% of the height differences would be due to genes rather than to environmental factors, such as nutrition.<\/p>\n<p>&nbsp;<\/p>\n<p><strong>Complex processes<\/strong><\/p>\n<p>The researchers also suggest how the previously undiscovered variants might be contributing to physical traits. Tentatively, they found that these rare variants were slightly enriched in protein-coding regions of the genome, and that they had an increased likelihood of being disruptive to these regions, notes Terence Capellini, an evolutionary biologist at Harvard University in Cambridge, Massachusetts. This indicates that the rare variants might partly influence height by affecting protein-coding regions instead of the rest of the genome \u2014 the vast majority of which does not include instructions for making proteins, but might influence their expression.<\/p>\n<p>The rarity of the variants also suggests that natural selection could be weeding them out, perhaps because they are harmful in some way.<\/p>\n<p>The complexity of heritability means that understanding the roots of many common diseases \u2014 necessary if researchers are to develop effective therapies against them \u2014 will take considerably more time and money, and it could involve sequencing hundreds of thousands or even millions of whole genomes to identify the rare variants that explain a substantial portion of the illnesses\u2019 genetic components.<\/p>\n<p>The study reveals only the total amount of rare variants contributing to these common traits \u2014 not which ones are important, says Spector. \u201cThe next stage is to go and work out which of these rare variants are important for traits or diseases that you want to get a drug for.\u201d<\/p>\n<p>&nbsp;<\/p>\n<p>&nbsp;<\/p>\n<\/div>\n<p><span class=\"emphasis\">Nature<\/span>\u00a0<strong>568<\/strong>, 444-445 (2019)<\/p>\n<p>&nbsp;<\/p>\n<div class=\"emphasis\">doi: 10.1038\/d41586-019-01157-y<\/div>\n<p>&nbsp;<\/p>\n<p>&nbsp;<\/p>\n<p>&nbsp;<\/p>\n<p>(\uc6d0\ubb38: <a href=\"https:\/\/www.nature.com\/articles\/d41586-019-01157-y?utm_source=feedburner&amp;utm_medium=feed&amp;utm_campaign=Feed%3A+nature%2Frss%2Fcurrent+%28Nature+-+Issue%29\">\uc5ec\uae30<\/a>\ub97c \ud074\ub9ad\ud558\uc138\uc694~)<\/p>\n<p>&nbsp;<\/p>\n<p>&nbsp;<\/p>\n<p>&nbsp;<\/p>\n","protected":false},"excerpt":{"rendered":"<p>&nbsp; &nbsp; Analysis of 20,000 genomes reveals that rare gene variants can help to explain how the trait is inherited. &nbsp; Height is often inherited<a href=\"https:\/\/biochemistry.khu.ac.kr\/lab\/?p=3413\" class=\"more-link\">(more&#8230;)<\/a><\/p>\n","protected":false},"author":1,"featured_media":0,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"_monsterinsights_skip_tracking":false,"_monsterinsights_sitenote_active":false,"_monsterinsights_sitenote_note":"","_monsterinsights_sitenote_category":0,"_jetpack_newsletter_access":"","_jetpack_dont_email_post_to_subs":false,"_jetpack_newsletter_tier_id":0,"_jetpack_memberships_contains_paywalled_content":false,"_jetpack_memberships_contains_paid_content":false,"footnotes":"","jetpack_publicize_message":"","jetpack_publicize_feature_enabled":true,"jetpack_social_post_already_shared":true,"jetpack_social_options":{"image_generator_settings":{"template":"highway","default_image_id":0,"font":"","enabled":false},"version":2},"jetpack_post_was_ever_published":false},"categories":[33,29,30],"tags":[],"class_list":["post-3413","post","type-post","status-publish","format-standard","hentry","category-do-biology","category-lets-do-science","category-recent-science-news"],"aioseo_notices":[],"jetpack_publicize_connections":[],"jetpack_featured_media_url":"","jetpack-related-posts":[{"id":474,"url":"https:\/\/biochemistry.khu.ac.kr\/lab\/?p=474","url_meta":{"origin":3413,"position":0},"title":"Heredity beyond the gene","author":"biochemistry","date":"May 30, 2018","format":false,"excerpt":"\u00a0 \u00a0 (\uc6d0\ubb38) \u00a0 \u00a0 Nick Lane relishes Carl Zimmer\u2019s history of inherited traits in all their messiness, from genes and culture to epigenetics. \u00a0 \u00a0 Human chromosomes and a nucleus in a false-colour image taken by scanning electron microscope.Credit: Power and Syred\/SPL \u00a0 She Has Her Mother\u2019s Laugh: The\u2026","rel":"","context":"In &quot;Let's Do Biology!&quot;","block_context":{"text":"Let's Do Biology!","link":"https:\/\/biochemistry.khu.ac.kr\/lab\/?cat=33"},"img":{"alt_text":"","src":"","width":0,"height":0},"classes":[]},{"id":1027,"url":"https:\/\/biochemistry.khu.ac.kr\/lab\/?p=1027","url_meta":{"origin":3413,"position":1},"title":"Beyond epigenetics","author":"biochemistry","date":"July 2, 2018","format":false,"excerpt":"\u00a0 \u00a0 (\uc6d0\ubb38) \u00a0 \u00a0 Extended Heredity: A New Understanding of Inheritance and Evolution\u00a0Russell Bonduriansky and Troy Day\u00a0Princeton University Press, 2018. 302 pp. \u00a0 \u00a0 Science\u00a0\u00a029 Jun 2018: Vol. 360, Issue 6396, pp. 1408 DOI: 10.1126\/science.aau1392 \u00a0 \u00a0 \u00a0 In the 19th century, August Weismann severed the tails of mice,\u2026","rel":"","context":"In &quot;Essays on Science&quot;","block_context":{"text":"Essays on Science","link":"https:\/\/biochemistry.khu.ac.kr\/lab\/?cat=32"},"img":{"alt_text":"","src":"","width":0,"height":0},"classes":[]},{"id":2580,"url":"https:\/\/biochemistry.khu.ac.kr\/lab\/?p=2580","url_meta":{"origin":3413,"position":2},"title":"On the road to a gene drive in mammals","author":"biochemistry","date":"January 29, 2019","format":false,"excerpt":"\u00a0 \u00a0 A method for making a version of a gene more likely to be inherited than normal, generating what is called a gene drive, might be used to control insect populations. 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