Nature Communications (Jun 2021)

Determinants of penetrance and variable expressivity in monogenic metabolic conditions across 77,184 exomes

  • Julia K. Goodrich,
  • Moriel Singer-Berk,
  • Rachel Son,
  • Abigail Sveden,
  • Jordan Wood,
  • Eleina England,
  • Joanne B. Cole,
  • Ben Weisburd,
  • Nick Watts,
  • Lizz Caulkins,
  • Peter Dornbos,
  • Ryan Koesterer,
  • Zachary Zappala,
  • Haichen Zhang,
  • Kristin A. Maloney,
  • Andy Dahl,
  • Carlos A. Aguilar-Salinas,
  • Gil Atzmon,
  • Francisco Barajas-Olmos,
  • Nir Barzilai,
  • John Blangero,
  • Eric Boerwinkle,
  • Lori L. Bonnycastle,
  • Erwin Bottinger,
  • Donald W. Bowden,
  • Federico Centeno-Cruz,
  • John C. Chambers,
  • Nathalie Chami,
  • Edmund Chan,
  • Juliana Chan,
  • Ching-Yu Cheng,
  • Yoon Shin Cho,
  • Cecilia Contreras-Cubas,
  • Emilio Córdova,
  • Adolfo Correa,
  • Ralph A. DeFronzo,
  • Ravindranath Duggirala,
  • Josée Dupuis,
  • Ma Eugenia Garay-Sevilla,
  • Humberto García-Ortiz,
  • Christian Gieger,
  • Benjamin Glaser,
  • Clicerio González-Villalpando,
  • Ma Elena Gonzalez,
  • Niels Grarup,
  • Leif Groop,
  • Myron Gross,
  • Christopher Haiman,
  • Sohee Han,
  • Craig L. Hanis,
  • Torben Hansen,
  • Nancy L. Heard-Costa,
  • Brian E. Henderson,
  • Juan Manuel Malacara Hernandez,
  • Mi Yeong Hwang,
  • Sergio Islas-Andrade,
  • Marit E. Jørgensen,
  • Hyun Min Kang,
  • Bong-Jo Kim,
  • Young Jin Kim,
  • Heikki A. Koistinen,
  • Jaspal Singh Kooner,
  • Johanna Kuusisto,
  • Soo-Heon Kwak,
  • Markku Laakso,
  • Leslie Lange,
  • Jong-Young Lee,
  • Juyoung Lee,
  • Donna M. Lehman,
  • Allan Linneberg,
  • Jianjun Liu,
  • Ruth J. F. Loos,
  • Valeriya Lyssenko,
  • Ronald C. W. Ma,
  • Angélica Martínez-Hernández,
  • James B. Meigs,
  • Thomas Meitinger,
  • Elvia Mendoza-Caamal,
  • Karen L. Mohlke,
  • Andrew D. Morris,
  • Alanna C. Morrison,
  • Maggie C. Y. Ng,
  • Peter M. Nilsson,
  • Christopher J. O’Donnell,
  • Lorena Orozco,
  • Colin N. A. Palmer,
  • Kyong Soo Park,
  • Wendy S. Post,
  • Oluf Pedersen,
  • Michael Preuss,
  • Bruce M. Psaty,
  • Alexander P. Reiner,
  • Cristina Revilla-Monsalve,
  • Stephen S. Rich,
  • Jerome I. Rotter,
  • Danish Saleheen,
  • Claudia Schurmann,
  • Xueling Sim,
  • Rob Sladek,
  • Kerrin S. Small,
  • Wing Yee So,
  • Timothy D. Spector,
  • Konstantin Strauch,
  • Tim M. Strom,
  • E. Shyong Tai,
  • Claudia H. T. Tam,
  • Yik Ying Teo,
  • Farook Thameem,
  • Brian Tomlinson,
  • Russell P. Tracy,
  • Tiinamaija Tuomi,
  • Jaakko Tuomilehto,
  • Teresa Tusié-Luna,
  • Rob M. van Dam,
  • Ramachandran S. Vasan,
  • James G. Wilson,
  • Daniel R. Witte,
  • Tien-Yin Wong,
  • AMP-T2D-GENES Consortia,
  • Noël P. Burtt,
  • Noah Zaitlen,
  • Mark I. McCarthy,
  • Michael Boehnke,
  • Toni I. Pollin,
  • Jason Flannick,
  • Josep M. Mercader,
  • Anne O’Donnell-Luria,
  • Samantha Baxter,
  • Jose C. Florez,
  • Daniel G. MacArthur,
  • Miriam S. Udler

DOI
https://doi.org/10.1038/s41467-021-23556-4
Journal volume & issue
Vol. 12, no. 1
pp. 1 – 15

Abstract

Read online

Penetrance of variants in monogenic disease and clinical utility of common polygenic variation has not been well explored on a large-scale. Here, the authors use exome sequencing data from 77,184 individuals to generate penetrance estimates and assess the utility of polygenic variation in risk prediction of monogenic variants.