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: Common single-nucleotide polymorphisms (SNPs) are predicted to collectively explain 40-50% of phenotypic variation in human height, but identifying the specific variants and associated regions requires huge sample sizes1. Here, using data from a genome-wide association study of 5.4 million individuals of diverse ancestries, we show that 12,111 independent SNPs that are significantly associated with height account for nearly all of the common SNP-based heritability. These SNPs are clustered within 7,209 non-overlapping genomic segments with a mean size of around 90 kb, covering about 21% of the genome. The density of independent associations varies across the genome and the regions of increased density are enriched for biologically relevant genes. In out-of-sample estimation and prediction, the 12,111 SNPs (or all SNPs in the HapMap 3 panel2) account for 40% (45%) of phenotypic variance in populations of European ancestry but only around 10-20% (14-24%) in populations of other ancestries. Effect sizes, associated regions and gene prioritization are similar across ancestries, indicating that reduced prediction accuracy is likely to be explained by linkage disequilibrium and differences in allele frequency within associated regions. Finally, we show that the relevant biological pathways are detectable with smaller sample sizes than are needed to implicate causal genes and variants. Overall, this study provides a comprehensive map of specific genomic regions that contain the vast majority of common height-associated variants. Although this map is saturated for populations of European ancestry, further research is needed to achieve equivalent saturation in other ancestries.
A saturated map of common genetic variants associated with human height
Yengo, Loïc;Vedantam, Sailaja;Marouli, Eirini;Sidorenko, Julia;Bartell, Eric;Sakaue, Saori;Graff, Marielisa;Eliasen, Anders U;Jiang, Yunxuan;Raghavan, Sridharan;Miao, Jenkai;Arias, Joshua D;Graham, Sarah E;Mukamel, Ronen E;Spracklen, Cassandra N;Yin, Xianyong;Chen, Shyh-Huei;Ferreira, Teresa;Highland, Heather H;Ji, Yingjie;Karaderi, Tugce;Lin, Kuang;Lüll, Kreete;Malden, Deborah E;Medina-Gomez, Carolina;Machado, Moara;Moore, Amy;Rüeger, Sina;Sim, Xueling;Vrieze, Scott;Ahluwalia, Tarunveer S;Akiyama, Masato;Allison, Matthew A;Alvarez, Marcus;Andersen, Mette K;Ani, Alireza;Appadurai, Vivek;Arbeeva, Liubov;Bhaskar, Seema;Bielak, Lawrence F;Bollepalli, Sailalitha;Bonnycastle, Lori L;Bork-Jensen, Jette;Bradfield, Jonathan P;Bradford, Yuki;Braund, Peter S;Brody, Jennifer A;Burgdorf, Kristoffer S;Cade, Brian E;Cai, Hui;Cai, Qiuyin;Campbell, Archie;Cañadas-Garre, Marisa;Catamo, Eulalia;Chai, Jin-Fang;Chai, Xiaoran;Chang, Li-Ching;Chang, Yi-Cheng;Chen, Chien-Hsiun;Chesi, Alessandra;Choi, Seung Hoan;Chung, Ren-Hua;Cocca, Massimiliano;Concas, Maria Pina;Couture, Christian;Cuellar-Partida, Gabriel;Danning, Rebecca;Daw, E Warwick;Degenhard, Frauke;Delgado, Graciela E;Delitala, Alessandro;Demirkan, Ayse;Deng, Xuan;Devineni, Poornima;Dietl, Alexander;Dimitriou, Maria;Dimitrov, Latchezar;Dorajoo, Rajkumar;Ekici, Arif B;Engmann, Jorgen E;Fairhurst-Hunter, Zammy;Farmaki, Aliki-Eleni;Faul, Jessica D;Fernandez-Lopez, Juan-Carlos;Forer, Lukas;Francescatto, Margherita;Freitag-Wolf, Sandra;Fuchsberger, Christian;Galesloot, Tessel E;Gao, Yan;Gao, Zishan;Geller, Frank;Giannakopoulou, Olga;Giulianini, Franco;Gjesing, Anette P;Goel, Anuj;Gordon, Scott D;Gorski, Mathias;Grove, Jakob;Guo, Xiuqing;Gustafsson, Stefan;Haessler, Jeffrey;Hansen, Thomas F;Havulinna, Aki S;Haworth, Simon J;He, Jing;Heard-Costa, Nancy;Hebbar, Prashantha;Hindy, George;Ho, Yuk-Lam A;Hofer, Edith;Holliday, Elizabeth;Horn, Katrin;Hornsby, Whitney E;Hottenga, Jouke-Jan;Huang, Hongyan;Huang, Jie;Huerta-Chagoya, Alicia;Huffman, Jennifer E;Hung, Yi-Jen;Huo, Shaofeng;Hwang, Mi Yeong;Iha, Hiroyuki;Ikeda, Daisuke D;Isono, Masato;Jackson, Anne U;Jäger, Susanne;Jansen, Iris E;Johansson, Ingegerd;Jonas, Jost B;Jonsson, Anna;Jørgensen, Torben;Kalafati, Ioanna-Panagiota;Kanai, Masahiro;Kanoni, Stavroula;Kårhus, Line L;Kasturiratne, Anuradhani;Katsuya, Tomohiro;Kawaguchi, Takahisa;Kember, Rachel L;Kentistou, Katherine A;Kim, Han-Na;Kim, Young Jin;Kleber, Marcus E;Knol, Maria J;Kurbasic, Azra;Lauzon, Marie;Le, Phuong;Lea, Rodney;Lee, Jong-Young;Leonard, Hampton L;Li, Shengchao A;Li, Xiaohui;Li, Xiaoyin;Liang, Jingjing;Lin, Honghuang;Lin, Shih-Yi;Liu, Jun;Liu, Xueping;Lo, Ken Sin;Long, Jirong;Lores-Motta, Laura;Luan, Jian'an;Lyssenko, Valeriya;Lyytikäinen, Leo-Pekka;Mahajan, Anubha;Mamakou, Vasiliki;Mangino, Massimo;Manichaikul, Ani;Marten, Jonathan;Mattheisen, Manuel;Mavarani, Laven;McDaid, Aaron F;Meidtner, Karina;Melendez, Tori L;Mercader, Josep M;Milaneschi, Yuri;Miller, Jason E;Millwood, Iona Y;Mishra, Pashupati P;Mitchell, Ruth E;Møllehave, Line T;Morgan, Anna;Mucha, Soeren;Munz, Matthias;Nakatochi, Masahiro;Nelson, Christopher P;Nethander, Maria;Nho, Chu Won;Nielsen, Aneta A;Nolte, Ilja M;Nongmaithem, Suraj S;Noordam, Raymond;Ntalla, Ioanna;Nutile, Teresa;Pandit, Anita;Christofidou, Paraskevi;Pärna, Katri;Pauper, Marc;Petersen, Eva R B;Petersen, Liselotte V;Pitkänen, Niina;Polašek, Ozren;Poveda, Alaitz;Preuss, Michael H;Pyarajan, Saiju;Raffield, Laura M;Rakugi, Hiromi;Ramirez, Julia;Rasheed, Asif;Raven, Dennis;Rayner, Nigel W;Riveros, Carlos;Rohde, Rebecca;Ruggiero, Daniela;Ruotsalainen, Sanni E;Ryan, Kathleen A;Sabater-Lleal, Maria;Saxena, Richa;Scholz, Markus;Sendamarai, Anoop;Shen, Botong;Shi, Jingchunzi;Shin, Jae Hun;Sidore, Carlo;Sitlani, Colleen M;Slieker, Roderick C;Smit, Roelof A J;Smith, Albert V;Smith, Jennifer A;Smyth, Laura J;Southam, Lorraine;Steinthorsdottir, Valgerdur;Sun, Liang;Takeuchi, Fumihiko;Tallapragada, Divya Sri Priyanka;Taylor, Kent D;Tayo, Bamidele O;Tcheandjieu, Catherine;Terzikhan, Natalie;Tesolin, Paola;Teumer, Alexander;Theusch, Elizabeth;Thompson, Deborah J;Thorleifsson, Gudmar;Timmers, Paul R H J;Trompet, Stella;Turman, Constance;Vaccargiu, Simona;van der Laan, Sander W;van der Most, Peter J;van Klinken, Jan B;van Setten, Jessica;Verma, Shefali S;Verweij, Niek;Veturi, Yogasudha;Wang, Carol A;Wang, Chaolong;Wang, Lihua;Wang, Zhe;Warren, Helen R;Bin Wei, Wen;Wickremasinghe, Ananda R;Wielscher, Matthias;Wiggins, Kerri L;Winsvold, Bendik S;Wong, Andrew;Wu, Yang;Wuttke, Matthias;Xia, Rui;Xie, Tian;Yamamoto, Ken;Yang, Jingyun;Yao, Jie;Young, Hannah;Yousri, Noha A;Yu, Lei;Zeng, Lingyao;Zhang, Weihua;Zhang, Xinyuan;Zhao, Jing-Hua;Zhao, Wei;Zhou, Wei;Zimmermann, Martina E;Zoledziewska, Magdalena;Adair, Linda S;Adams, Hieab H H;Aguilar-Salinas, Carlos A;Al-Mulla, Fahd;Arnett, Donna K;Asselbergs, Folkert W;Åsvold, Bjørn Olav;Attia, John;Banas, Bernhard;Bandinelli, Stefania;Bennett, David A;Bergler, Tobias;Bharadwaj, Dwaipayan;Biino, Ginevra;Bisgaard, Hans;Boerwinkle, Eric;Böger, Carsten A;Bønnelykke, Klaus;Boomsma, Dorret I;Børglum, Anders D;Borja, Judith B;Bouchard, Claude;Bowden, Donald W;Brandslund, Ivan;Brumpton, Ben;Buring, Julie E;Caulfield, Mark J;Chambers, John C;Chandak, Giriraj R;Chanock, Stephen J;Chaturvedi, Nish;Chen, Yii-Der Ida;Chen, Zhengming;Cheng, Ching-Yu;Christophersen, Ingrid E;Ciullo, Marina;Cole, John W;Collins, Francis S;Cooper, Richard S;Cruz, Miguel;Cucca, Francesco;Cupples, L Adrienne;Cutler, Michael J;Damrauer, Scott M;Dantoft, Thomas M;de Borst, Gert J;de Groot, Lisette C P G M;De Jager, Philip L;de Kleijn, Dominique P V;Janaka de Silva, H;Dedoussis, George V;den Hollander, Anneke I;Du, Shufa;Easton, Douglas F;Elders, Petra J M;Eliassen, A Heather;Ellinor, Patrick T;Elmståhl, Sölve;Erdmann, Jeanette;Evans, Michele K;Fatkin, Diane;Feenstra, Bjarke;Feitosa, Mary F;Ferrucci, Luigi;Ford, Ian;Fornage, Myriam;Franke, Andre;Franks, Paul W;Freedman, Barry I;Gasparini, Paolo;Gieger, Christian;Girotto, Giorgia;Goddard, Michael E;Golightly, Yvonne M;Gonzalez-Villalpando, Clicerio;Gordon-Larsen, Penny;Grallert, Harald;Grant, Struan F A;Grarup, Niels;Griffiths, Lyn;Gudnason, Vilmundur;Haiman, Christopher;Hakonarson, Hakon;Hansen, Torben;Hartman, Catharina A;Hattersley, Andrew T;Hayward, Caroline;Heckbert, Susan R;Heng, Chew-Kiat;Hengstenberg, Christian;Hewitt, Alex W;Hishigaki, Haretsugu;Hoyng, Carel B;Huang, Paul L;Huang, Wei;Hunt, Steven C;Hveem, Kristian;Hyppönen, Elina;Iacono, William G;Ichihara, Sahoko;Ikram, M Arfan;Isasi, Carmen R;Jackson, Rebecca D;Jarvelin, Marjo-Riitta;Jin, Zi-Bing;Jöckel, Karl-Heinz;Joshi, Peter K;Jousilahti, Pekka;Jukema, J Wouter;Kähönen, Mika;Kamatani, Yoichiro;Kang, Kui Dong;Kaprio, Jaakko;Kardia, Sharon L R;Karpe, Fredrik;Kato, Norihiro;Kee, Frank;Kessler, Thorsten;Khera, Amit V;Khor, Chiea Chuen;Kiemeney, Lambertus A L M;Kim, Bong-Jo;Kim, Eung Kweon;Kim, Hyung-Lae;Kirchhof, Paulus;Kivimaki, Mika;Koh, Woon-Puay;Koistinen, Heikki A;Kolovou, Genovefa D;Kooner, Jaspal S;Kooperberg, Charles;Köttgen, Anna;Kovacs, Peter;Kraaijeveld, Adriaan;Kraft, Peter;Krauss, Ronald M;Kumari, Meena;Kutalik, Zoltan;Laakso, Markku;Lange, Leslie A;Langenberg, Claudia;Launer, Lenore J;Le Marchand, Loic;Lee, Hyejin;Lee, Nanette R;Lehtimäki, Terho;Li, Huaixing;Li, Liming;Lieb, Wolfgang;Lin, Xu;Lind, Lars;Linneberg, Allan;Liu, Ching-Ti;Liu, Jianjun;Loeffler, Markus;London, Barry;Lubitz, Steven A;Lye, Stephen J;Mackey, David A;Mägi, Reedik;Magnusson, Patrik K E;Marcus, Gregory M;Vidal, Pedro Marques;Martin, Nicholas G;März, Winfried;Matsuda, Fumihiko;McGarrah, Robert W;McGue, Matt;McKnight, Amy Jayne;Medland, Sarah E;Mellström, Dan;Metspalu, Andres;Mitchell, Braxton D;Mitchell, Paul;Mook-Kanamori, Dennis O;Morris, Andrew D;Mucci, Lorelei A;Munroe, Patricia B;Nalls, Mike A;Nazarian, Saman;Nelson, Amanda E;Neville, Matt J;Newton-Cheh, Christopher;Nielsen, Christopher S;Nöthen, Markus M;Ohlsson, Claes;Oldehinkel, Albertine J;Orozco, Lorena;Pahkala, Katja;Pajukanta, Päivi;Palmer, Colin N A;Parra, Esteban J;Pattaro, Cristian;Pedersen, Oluf;Pennell, Craig E;Penninx, Brenda W J H;Perusse, Louis;Peters, Annette;Peyser, Patricia A;Porteous, David J;Posthuma, Danielle;Power, Chris;Pramstaller, Peter P;Province, Michael A;Qi, Qibin;Qu, Jia;Rader, Daniel J;Raitakari, Olli T;Ralhan, Sarju;Rallidis, Loukianos S;Rao, Dabeeru C;Redline, Susan;Reilly, Dermot F;Reiner, Alexander P;Rhee, Sang Youl;Ridker, Paul M;Rienstra, Michiel;Ripatti, Samuli;Ritchie, Marylyn D;Roden, Dan M;Rosendaal, Frits R;Rotter, Jerome I;Rudan, Igor;Rutters, Femke;Sabanayagam, Charumathi;Saleheen, Danish;Salomaa, Veikko;Samani, Nilesh J;Sanghera, Dharambir K;Sattar, Naveed;Schmidt, Börge;Schmidt, Helena;Schmidt, Reinhold;Schulze, Matthias B;Schunkert, Heribert;Scott, Laura J;Scott, Rodney J;Sever, Peter;Shiroma, Eric J;Shoemaker, M Benjamin;Shu, Xiao-Ou;Simonsick, Eleanor M;Sims, Mario;Singh, Jai Rup;Singleton, Andrew B;Sinner, Moritz F;Smith, J Gustav;Snieder, Harold;Spector, Tim D;Stampfer, Meir J;Stark, Klaus J;Strachan, David P;'t Hart, Leen M;Tabara, Yasuharu;Tang, Hua;Tardif, Jean-Claude;Thanaraj, Thangavel A;Timpson, Nicholas J;Tönjes, Anke;Tremblay, Angelo;Tuomi, Tiinamaija;Tuomilehto, Jaakko;Tusié-Luna, Maria-Teresa;Uitterlinden, Andre G;van Dam, Rob M;van der Harst, Pim;Van der Velde, Nathalie;van Duijn, Cornelia M;van Schoor, Natasja M;Vitart, Veronique;Völker, Uwe;Vollenweider, Peter;Völzke, Henry;Wacher-Rodarte, Niels H;Walker, Mark;Wang, Ya Xing;Wareham, Nicholas J;Watanabe, Richard M;Watkins, Hugh;Weir, David R;Werge, Thomas M;Widen, Elisabeth;Wilkens, Lynne R;Willemsen, Gonneke;Willett, Walter C;Wilson, James F;Wong, Tien-Yin;Woo, Jeong-Taek;Wright, Alan F;Wu, Jer-Yuarn;Xu, Huichun;Yajnik, Chittaranjan S;Yokota, Mitsuhiro;Yuan, Jian-Min;Zeggini, Eleftheria;Zemel, Babette S;Zheng, Wei;Zhu, Xiaofeng;Zmuda, Joseph M;Zonderman, Alan B;Zwart, John-Anker;Chasman, Daniel I;Cho, Yoon Shin;Heid, Iris M;McCarthy, Mark I;Ng, Maggie C Y;O'Donnell, Christopher J;Rivadeneira, Fernando;Thorsteinsdottir, Unnur;Sun, Yan V;Tai, E Shyong;Boehnke, Michael;Deloukas, Panos;Justice, Anne E;Lindgren, Cecilia M;Loos, Ruth J F;Mohlke, Karen L;North, Kari E;Stefansson, Kari;Walters, Robin G;Winkler, Thomas W;Young, Kristin L;Loh, Po-Ru;Yang, Jian;Esko, Tõnu;Assimes, Themistocles L;Auton, Adam;Abecasis, Goncalo R;Willer, Cristen J;Locke, Adam E;Berndt, Sonja I;Lettre, Guillaume;Frayling, Timothy M;Okada, Yukinori;Wood, Andrew R;Visscher, Peter M;Hirschhorn, Joel N
2022
Abstract
: Common single-nucleotide polymorphisms (SNPs) are predicted to collectively explain 40-50% of phenotypic variation in human height, but identifying the specific variants and associated regions requires huge sample sizes1. Here, using data from a genome-wide association study of 5.4 million individuals of diverse ancestries, we show that 12,111 independent SNPs that are significantly associated with height account for nearly all of the common SNP-based heritability. These SNPs are clustered within 7,209 non-overlapping genomic segments with a mean size of around 90 kb, covering about 21% of the genome. The density of independent associations varies across the genome and the regions of increased density are enriched for biologically relevant genes. In out-of-sample estimation and prediction, the 12,111 SNPs (or all SNPs in the HapMap 3 panel2) account for 40% (45%) of phenotypic variance in populations of European ancestry but only around 10-20% (14-24%) in populations of other ancestries. Effect sizes, associated regions and gene prioritization are similar across ancestries, indicating that reduced prediction accuracy is likely to be explained by linkage disequilibrium and differences in allele frequency within associated regions. Finally, we show that the relevant biological pathways are detectable with smaller sample sizes than are needed to implicate causal genes and variants. Overall, this study provides a comprehensive map of specific genomic regions that contain the vast majority of common height-associated variants. Although this map is saturated for populations of European ancestry, further research is needed to achieve equivalent saturation in other ancestries.
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/20.500.14243/472461
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simulazione ASN
Il report seguente simula gli indicatori relativi alla propria produzione scientifica in relazione alle soglie ASN 2023-2025 del proprio SC/SSD. Si ricorda che il superamento dei valori soglia (almeno 2 su 3) è requisito necessario ma non sufficiente al conseguimento dell'abilitazione. La simulazione si basa sui dati IRIS e sugli indicatori bibliometrici alla data indicata e non tiene conto di eventuali periodi di congedo obbligatorio, che in sede di domanda ASN danno diritto a incrementi percentuali dei valori. La simulazione può differire dall'esito di un’eventuale domanda ASN sia per errori di catalogazione e/o dati mancanti in IRIS, sia per la variabilità dei dati bibliometrici nel tempo. Si consideri che Anvur calcola i valori degli indicatori all'ultima data utile per la presentazione delle domande.
La presente simulazione è stata realizzata sulla base delle specifiche raccolte sul tavolo ER del Focus Group IRIS coordinato dall'Università di Modena e Reggio Emilia e delle regole riportate nel DM 589/2018 e allegata Tabella A. Cineca, l'Università di Modena e Reggio Emilia e il Focus Group IRIS non si assumono alcuna responsabilità in merito all’uso che il diretto interessato o terzi faranno della simulazione. Si specifica inoltre che la simulazione contiene calcoli effettuati con dati e algoritmi di pubblico dominio e deve quindi essere considerata come un mero ausilio al calcolo svolgibile manualmente o con strumenti equivalenti.