Por favor, use este identificador para citar o enlazar este Item:http://hdl.handle.net/20.500.12105/14737
Título
Determinants of penetrance and variable expressivity in monogenic metabolic conditions across 77,184 exomes
Autor(es)
Goodrich, Julia K | Singer-Berk, Moriel | Son, Rachel | Sveden, Abigail | Wood, Jordan | England, Eleina | Cole, Joanne B | Weisburd, Ben | Watts, Nick | Caulkins, Lizz | Dornbos, Peter | Koesterer, Ryan | Zappala, Zachary | Zhang, Haichen | Maloney, Kristin A | Dahl, Andy | Aguilar-Salinas, Carlos A | Atzmon, Gil | Barajas-Olmos, Francisco | Barzilai, Nir | Blangero, John | Boerwinkle, Eric | Bonnycastle, Lori L | Bottinger, Erwin | Bowden, Donald W | Centeno-Cruz, Federico | Chambers, John C | Chami, Nathalie | Chan, Edmund | Chan, Juliana | Cheng, Ching-Yu | Cho, Yoon Shin | Contreras-Cubas, Cecilia | Córdova, Emilio | Correa, Adolfo | DeFronzo, Ralph A | Duggirala, Ravindranath | Dupuis, Josée | Garay-Sevilla, María Eugenia | García-Ortiz, Humberto | Gieger, Christian | Glaser, Benjamin | González-Villalpando, Clicerio | Gonzalez, Ma Elena | Grarup, Niels | Groop, Leif | Gross, Myron | Haiman, Christopher | Han, Sohee | Hanis, Craig L | Hansen, Torben | Heard-Costa, Nancy L | Henderson, Brian E | Malacara Hernández, Juan Manuel | Hwang, Mi Yeong | Islas-Andrade, Sergio | Jørgensen, Marit E | Kang, Hyun Min | Kim, Bong-Jo | Kim, Young Jin | Koistinen, Heikki A | Kooner, Jaspal Singh | Kuusisto, Johanna | Kwak, Soo-Heon | Laakso, Markku | Lange, Leslie | Lee, Jong-Young | Lee, Juyoung | Lehman, Donna M | Linneberg, Allan | Liu, Jianjun | Loos, Ruth JF | Lyssenko, Valeriya | Ma, Ronald CW | Martínez-Hernández, Angélica | Meigs, James B | Meitinger, Thomas | Mendoza-Caamal, Elvia | Mohlke, Karen L | Morris, Andrew D | Morrison, Alanna C | Ng, Maggie C Y | Nilsson, Peter M | O'Donnell, Christopher J | Orozco, Lorena | Palmer, Colin NA | Park, Kyong Soo | Post, Wendy S | Pedersen, Oluf | Preuss, Michael | Psaty, Bruce M | Reiner, Alexander P | Revilla-Monsalve, Cristina | Rich, Stephen S | Rotter, Jerome I | Saleheen, Danish | Schurmann, Claudia | Sim, Xueling | Sladek, Rob | Small, Kerrin S | So, Wing Yee | Spector, Timothy D | Strauch, Konstantin | Strom, Tim M | Tai, E Shyong | Tam, Claudia H T | Teo, Yik Ying | Thameem, Farook | Tomlinson, Brian | Tracy, Russell P | Tuomi, Tiinamaija | Tuomilehto, Jaakko ISCIII | Tusié-Luna, Teresa | van Dam, Rob M | Vasan, Ramachandran S | Wilson, James G | Witte, Daniel R | Wong, Tien-Yin | Burtt, Noël P | Zaitlen, Noah | McCarthy, Mark I | Boehnke, Michael | Pollin, Toni I | Flannick, Jason | Mercader, Josep M | O'Donnell-Luria, Anne | Baxter, Samantha | Florez, Jose C | MacArthur, Daniel G | Udler, Miriam S | AMP-T2D-GENES Consortia
Fecha de publicación
2021-06-09
Cita
Nat Commun. 2021 Jun 9;12(1):3505.
Idioma
Inglés
Tipo de documento
journal article
Resumen
Hundreds of thousands of genetic variants have been reported to cause severe monogenic diseases, but the probability that a variant carrier develops the disease (termed penetrance) is unknown for virtually all of them. Additionally, the clinical utility of common polygenetic variation remains uncertain. Using exome sequencing from 77,184 adult individuals (38,618 multi-ancestral individuals from a type 2 diabetes case-control study and 38,566 participants from the UK Biobank, for whom genotype array data were also available), we apply clinical standard-of-care gene variant curation for eight monogenic metabolic conditions. Rare variants causing monogenic diabetes and dyslipidemias display effect sizes significantly larger than the top 1% of the corresponding polygenic scores. Nevertheless, penetrance estimates for monogenic variant carriers average 60% or lower for most conditions. We assess epidemiologic and genetic factors contributing to risk prediction in monogenic variant carriers, demonstrating that inclusion of polygenic variation significantly improves biomarker estimation for two monogenic dyslipidemias.
MESH
Adult | Biological Variation, Population | Biomarkers | Diabetes Mellitus, Type 2 | Dyslipidemias | Exome | Genetic Predisposition to Disease | Genotype | Humans | Multifactorial Inheritance | Penetrance | Risk Assessment
Versión en línea
DOI
Aparece en las colecciones
Ficheros en el ítem
- Nombre:
- DeterminantsOfPenetranceAnd_20 ...
- Tamaño:
- 2.619Mb
- Formato:
- Descripción:
- Artículo principal
- Nombre:
- DeterminantsOfPenetranceAndDes ...
- Tamaño:
- 12.35Kb
- Formato:
- Microsoft Word 2007
- Descripción:
- Supplementary Information
- Nombre:
- DeterminantsOfPenetranceAndRep ...
- Tamaño:
- 360.0Kb
- Formato:
- Descripción:
- Supplementary Information
- Nombre:
- DeterminantsOfPenetranceAndSup ...
- Tamaño:
- 176.0Kb
- Formato:
- Microsoft Excel 2007
- Nombre:
- DeterminantsOfPenetranceAndSup ...
- Tamaño:
- 911.7Kb
- Formato:
- Descripción:
- Supplementary Information