Determinants of penetrance and variable expressivity in monogenic metabolic conditions across 77,184 exomes
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 predi...
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2021
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oai:doaj.org-article:20bcc638047441c3919ace2b384c06002021-12-02T17:47:17ZDeterminants of penetrance and variable expressivity in monogenic metabolic conditions across 77,184 exomes10.1038/s41467-021-23556-42041-1723https://doaj.org/article/20bcc638047441c3919ace2b384c06002021-06-01T00:00:00Zhttps://doi.org/10.1038/s41467-021-23556-4https://doaj.org/toc/2041-1723Penetrance 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.Julia K. GoodrichMoriel Singer-BerkRachel SonAbigail SvedenJordan WoodEleina EnglandJoanne B. ColeBen WeisburdNick WattsLizz CaulkinsPeter DornbosRyan KoestererZachary ZappalaHaichen ZhangKristin A. MaloneyAndy DahlCarlos A. Aguilar-SalinasGil AtzmonFrancisco Barajas-OlmosNir BarzilaiJohn BlangeroEric BoerwinkleLori L. BonnycastleErwin BottingerDonald W. BowdenFederico Centeno-CruzJohn C. ChambersNathalie ChamiEdmund ChanJuliana ChanChing-Yu ChengYoon Shin ChoCecilia Contreras-CubasEmilio CórdovaAdolfo CorreaRalph A. DeFronzoRavindranath DuggiralaJosée DupuisMa Eugenia Garay-SevillaHumberto García-OrtizChristian GiegerBenjamin GlaserClicerio González-VillalpandoMa Elena GonzalezNiels GrarupLeif GroopMyron GrossChristopher HaimanSohee HanCraig L. HanisTorben HansenNancy L. Heard-CostaBrian E. HendersonJuan Manuel Malacara HernandezMi Yeong HwangSergio Islas-AndradeMarit E. JørgensenHyun Min KangBong-Jo KimYoung Jin KimHeikki A. KoistinenJaspal Singh KoonerJohanna KuusistoSoo-Heon KwakMarkku LaaksoLeslie LangeJong-Young LeeJuyoung LeeDonna M. LehmanAllan LinnebergJianjun LiuRuth J. F. LoosValeriya LyssenkoRonald C. W. MaAngélica Martínez-HernándezJames B. MeigsThomas MeitingerElvia Mendoza-CaamalKaren L. MohlkeAndrew D. MorrisAlanna C. MorrisonMaggie C. Y. NgPeter M. NilssonChristopher J. O’DonnellLorena OrozcoColin N. A. PalmerKyong Soo ParkWendy S. PostOluf PedersenMichael PreussBruce M. PsatyAlexander P. ReinerCristina Revilla-MonsalveStephen S. RichJerome I. RotterDanish SaleheenClaudia SchurmannXueling SimRob SladekKerrin S. SmallWing Yee SoTimothy D. SpectorKonstantin StrauchTim M. StromE. Shyong TaiClaudia H. T. TamYik Ying TeoFarook ThameemBrian TomlinsonRussell P. TracyTiinamaija TuomiJaakko TuomilehtoTeresa Tusié-LunaRob M. van DamRamachandran S. VasanJames G. WilsonDaniel R. WitteTien-Yin WongAMP-T2D-GENES ConsortiaNoël P. BurttNoah ZaitlenMark I. McCarthyMichael BoehnkeToni I. PollinJason FlannickJosep M. MercaderAnne O’Donnell-LuriaSamantha BaxterJose C. FlorezDaniel G. MacArthurMiriam S. UdlerNature PortfolioarticleScienceQENNature Communications, Vol 12, Iss 1, Pp 1-15 (2021) |
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DOAJ |
| collection |
DOAJ |
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EN |
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Science Q |
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Science Q 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 Determinants of penetrance and variable expressivity in monogenic metabolic conditions across 77,184 exomes |
| description |
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. |
| format |
article |
| author |
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 |
| author_facet |
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 |
| author_sort |
Julia K. Goodrich |
| title |
Determinants of penetrance and variable expressivity in monogenic metabolic conditions across 77,184 exomes |
| title_short |
Determinants of penetrance and variable expressivity in monogenic metabolic conditions across 77,184 exomes |
| title_full |
Determinants of penetrance and variable expressivity in monogenic metabolic conditions across 77,184 exomes |
| title_fullStr |
Determinants of penetrance and variable expressivity in monogenic metabolic conditions across 77,184 exomes |
| title_full_unstemmed |
Determinants of penetrance and variable expressivity in monogenic metabolic conditions across 77,184 exomes |
| title_sort |
determinants of penetrance and variable expressivity in monogenic metabolic conditions across 77,184 exomes |
| publisher |
Nature Portfolio |
| publishDate |
2021 |
| url |
https://doaj.org/article/20bcc638047441c3919ace2b384c0600 |
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