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Associations of autozygosity with a broad range of human phenotypes.


ABSTRACT: In many species, the offspring of related parents suffer reduced reproductive success, a phenomenon known as inbreeding depression. In humans, the importance of this effect has remained unclear, partly because reproduction between close relatives is both rare and frequently associated with confounding social factors. Here, using genomic inbreeding coefficients (FROH) for >1.4 million individuals, we show that FROH is significantly associated (p?

SUBMITTER: Clark DW 

PROVIDER: S-EPMC6823371 | biostudies-literature | 2019 Oct

REPOSITORIES: biostudies-literature

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Associations of autozygosity with a broad range of human phenotypes.

Clark David W DW   Okada Yukinori Y   Moore Kristjan H S KHS   Mason Dan D   Pirastu Nicola N   Gandin Ilaria I   Mattsson Hannele H   Barnes Catriona L K CLK   Lin Kuang K   Zhao Jing Hua JH   Deelen Patrick P   Rohde Rebecca R   Schurmann Claudia C   Guo Xiuqing X   Giulianini Franco F   Zhang Weihua W   Medina-Gomez Carolina C   Karlsson Robert R   Bao Yanchun Y   Bartz Traci M TM   Baumbach Clemens C   Biino Ginevra G   Bixley Matthew J MJ   Brumat Marco M   Chai Jin-Fang JF   Corre Tanguy T   Cousminer Diana L DL   Dekker Annelot M AM   Eccles David A DA   van Eijk Kristel R KR   Fuchsberger Christian C   Gao He H   Germain Marine M   Gordon Scott D SD   de Haan Hugoline G HG   Harris Sarah E SE   Hofer Edith E   Huerta-Chagoya Alicia A   Igartua Catherine C   Jansen Iris E IE   Jia Yucheng Y   Kacprowski Tim T   Karlsson Torgny T   Kleber Marcus E ME   Li Shengchao Alfred SA   Li-Gao Ruifang R   Mahajan Anubha A   Matsuda Koichi K   Meidtner Karina K   Meng Weihua W   Montasser May E ME   van der Most Peter J PJ   Munz Matthias M   Nutile Teresa T   Palviainen Teemu T   Prasad Gauri G   Prasad Rashmi B RB   Priyanka Tallapragada Divya Sri TDS   Rizzi Federica F   Salvi Erika E   Sapkota Bishwa R BR   Shriner Daniel D   Skotte Line L   Smart Melissa C MC   Smith Albert Vernon AV   van der Spek Ashley A   Spracklen Cassandra N CN   Strawbridge Rona J RJ   Tajuddin Salman M SM   Trompet Stella S   Turman Constance C   Verweij Niek N   Viberti Clara C   Wang Lihua L   Warren Helen R HR   Wootton Robyn E RE   Yanek Lisa R LR   Yao Jie J   Yousri Noha A NA   Zhao Wei W   Adeyemo Adebowale A AA   Afaq Saima S   Aguilar-Salinas Carlos Alberto CA   Akiyama Masato M   Albert Matthew L ML   Allison Matthew A MA   Alver Maris M   Aung Tin T   Azizi Fereidoun F   Bentley Amy R AR   Boeing Heiner H   Boerwinkle Eric E   Borja Judith B JB   de Borst Gert J GJ   Bottinger Erwin P EP   Broer Linda L   Campbell Harry H   Chanock Stephen S   Chee Miao-Li ML   Chen Guanjie G   Chen Yii-Der I YI   Chen Zhengming Z   Chiu Yen-Feng YF   Cocca Massimiliano M   Collins Francis S FS   Concas Maria Pina MP   Corley Janie J   Cugliari Giovanni G   van Dam Rob M RM   Damulina Anna A   Daneshpour Maryam S MS   Day Felix R FR   Delgado Graciela E GE   Dhana Klodian K   Doney Alexander S F ASF   Dörr Marcus M   Doumatey Ayo P AP   Dzimiri Nduna N   Ebenesersdóttir S Sunna SS   Elliott Joshua J   Elliott Paul P   Ewert Ralf R   Felix Janine F JF   Fischer Krista K   Freedman Barry I BI   Girotto Giorgia G   Goel Anuj A   Gögele Martin M   Goodarzi Mark O MO   Graff Mariaelisa M   Granot-Hershkovitz Einat E   Grodstein Francine F   Guarrera Simonetta S   Gudbjartsson Daniel F DF   Guity Kamran K   Gunnarsson Bjarni B   Guo Yu Y   Hagenaars Saskia P SP   Haiman Christopher A CA   Halevy Avner A   Harris Tamara B TB   Hedayati Mehdi M   van Heel David A DA   Hirata Makoto M   Höfer Imo I   Hsiung Chao Agnes CA   Huang Jinyan J   Hung Yi-Jen YJ   Ikram M Arfan MA   Jagadeesan Anuradha A   Jousilahti Pekka P   Kamatani Yoichiro Y   Kanai Masahiro M   Kerrison Nicola D ND   Kessler Thorsten T   Khaw Kay-Tee KT   Khor Chiea Chuen CC   de Kleijn Dominique P V DPV   Koh Woon-Puay WP   Kolcic Ivana I   Kraft Peter P   Krämer Bernhard K BK   Kutalik Zoltán Z   Kuusisto Johanna J   Langenberg Claudia C   Launer Lenore J LJ   Lawlor Deborah A DA   Lee I-Te IT   Lee Wen-Jane WJ   Lerch Markus M MM   Li Liming L   Liu Jianjun J   Loh Marie M   London Stephanie J SJ   Loomis Stephanie S   Lu Yingchang Y   Luan Jian'an J   Mägi Reedik R   Manichaikul Ani W AW   Manunta Paolo P   Másson Gísli G   Matoba Nana N   Mei Xue W XW   Meisinger Christa C   Meitinger Thomas T   Mezzavilla Massimo M   Milani Lili L   Millwood Iona Y IY   Momozawa Yukihide Y   Moore Amy A   Morange Pierre-Emmanuel PE   Moreno-Macías Hortensia H   Mori Trevor A TA   Morrison Alanna C AC   Muka Taulant T   Murakami Yoshinori Y   Murray Alison D AD   de Mutsert Renée R   Mychaleckyj Josyf C JC   Nalls Mike A MA   Nauck Matthias M   Neville Matt J MJ   Nolte Ilja M IM   Ong Ken K KK   Orozco Lorena L   Padmanabhan Sandosh S   Pálsson Gunnar G   Pankow James S JS   Pattaro Cristian C   Pattie Alison A   Polasek Ozren O   Poulter Neil N   Pramstaller Peter P PP   Quintana-Murci Lluis L   Räikkönen Katri K   Ralhan Sarju S   Rao Dabeeru C DC   van Rheenen Wouter W   Rich Stephen S SS   Ridker Paul M PM   Rietveld Cornelius A CA   Robino Antonietta A   van Rooij Frank J A FJA   Ruggiero Daniela D   Saba Yasaman Y   Sabanayagam Charumathi C   Sabater-Lleal Maria M   Sala Cinzia Felicita CF   Salomaa Veikko V   Sandow Kevin K   Schmidt Helena H   Scott Laura J LJ   Scott William R WR   Sedaghati-Khayat Bahareh B   Sennblad Bengt B   van Setten Jessica J   Sever Peter J PJ   Sheu Wayne H-H WH   Shi Yuan Y   Shrestha Smeeta S   Shukla Sharvari Rahul SR   Sigurdsson Jon K JK   Sikka Timo Tonis TT   Singh Jai Rup JR   Smith Blair H BH   Stančáková Alena A   Stanton Alice A   Starr John M JM   Stefansdottir Lilja L   Straker Leon L   Sulem Patrick P   Sveinbjornsson Gardar G   Swertz Morris A MA   Taylor Adele M AM   Taylor Kent D KD   Terzikhan Natalie N   Tham Yih-Chung YC   Thorleifsson Gudmar G   Thorsteinsdottir Unnur U   Tillander Annika A   Tracy Russell P RP   Tusié-Luna Teresa T   Tzoulaki Ioanna I   Vaccargiu Simona S   Vangipurapu Jagadish J   Veldink Jan H JH   Vitart Veronique V   Völker Uwe U   Vuoksimaa Eero E   Wakil Salma M SM   Waldenberger Melanie M   Wander Gurpreet S GS   Wang Ya Xing YX   Wareham Nicholas J NJ   Wild Sarah S   Yajnik Chittaranjan S CS   Yuan Jian-Min JM   Zeng Lingyao L   Zhang Liang L   Zhou Jie J   Amin Najaf N   Asselbergs Folkert W FW   Bakker Stephan J L SJL   Becker Diane M DM   Lehne Benjamin B   Bennett David A DA   van den Berg Leonard H LH   Berndt Sonja I SI   Bharadwaj Dwaipayan D   Bielak Lawrence F LF   Bochud Murielle M   Boehnke Mike M   Bouchard Claude C   Bradfield Jonathan P JP   Brody Jennifer A JA   Campbell Archie A   Carmi Shai S   Caulfield Mark J MJ   Cesarini David D   Chambers John C JC   Chandak Giriraj Ratan GR   Cheng Ching-Yu CY   Ciullo Marina M   Cornelis Marilyn M   Cusi Daniele D   Smith George Davey GD   Deary Ian J IJ   Dorajoo Rajkumar R   van Duijn Cornelia M CM   Ellinghaus David D   Erdmann Jeanette J   Eriksson Johan G JG   Evangelou Evangelos E   Evans Michele K MK   Faul Jessica D JD   Feenstra Bjarke B   Feitosa Mary M   Foisy Sylvain S   Franke Andre A   Friedlander Yechiel Y   Gasparini Paolo P   Gieger Christian C   Gonzalez Clicerio C   Goyette Philippe P   Grant Struan F A SFA   Griffiths Lyn R LR   Groop Leif L   Gudnason Vilmundur V   Gyllensten Ulf U   Hakonarson Hakon H   Hamsten Anders A   van der Harst Pim P   Heng Chew-Kiat CK   Hicks Andrew A AA   Hochner Hagit H   Huikuri Heikki H   Hunt Steven C SC   Jaddoe Vincent W V VWV   De Jager Philip L PL   Johannesson Magnus M   Johansson Åsa Å   Jonas Jost B JB   Jukema J Wouter JW   Junttila Juhani J   Kaprio Jaakko J   Kardia Sharon L R SLR   Karpe Fredrik F   Kumari Meena M   Laakso Markku M   van der Laan Sander W SW   Lahti Jari J   Laudes Matthias M   Lea Rodney A RA   Lieb Wolfgang W   Lumley Thomas T   Martin Nicholas G NG   März Winfried W   Matullo Giuseppe G   McCarthy Mark I MI   Medland Sarah E SE   Merriman Tony R TR   Metspalu Andres A   Meyer Brian F BF   Mohlke Karen L KL   Montgomery Grant W GW   Mook-Kanamori Dennis D   Munroe Patricia B PB   North Kari E KE   Nyholt Dale R DR   O'connell Jeffery R JR   Ober Carole C   Oldehinkel Albertine J AJ   Palmas Walter W   Palmer Colin C   Pasterkamp Gerard G GG   Patin Etienne E   Pennell Craig E CE   Perusse Louis L   Peyser Patricia A PA   Pirastu Mario M   Polderman Tinca J C TJC   Porteous David J DJ   Posthuma Danielle D   Psaty Bruce M BM   Rioux John D JD   Rivadeneira Fernando F   Rotimi Charles C   Rotter Jerome I JI   Rudan Igor I   Den Ruijter Hester M HM   Sanghera Dharambir K DK   Sattar Naveed N   Schmidt Reinhold R   Schulze Matthias B MB   Schunkert Heribert H   Scott Robert A RA   Shuldiner Alan R AR   Sim Xueling X   Small Neil N   Smith Jennifer A JA   Sotoodehnia Nona N   Tai E-Shyong ES   Teumer Alexander A   Timpson Nicholas J NJ   Toniolo Daniela D   Tregouet David-Alexandre DA   Tuomi Tiinamaija T   Vollenweider Peter P   Wang Carol A CA   Weir David R DR   Whitfield John B JB   Wijmenga Cisca C   Wong Tien-Yin TY   Wright John J   Yang Jingyun J   Yu Lei L   Zemel Babette S BS   Zonderman Alan B AB   Perola Markus M   Magnusson Patrik K E PKE   Uitterlinden André G AG   Kooner Jaspal S JS   Chasman Daniel I DI   Loos Ruth J F RJF   Franceschini Nora N   Franke Lude L   Haley Chris S CS   Hayward Caroline C   Walters Robin G RG   Perry John R B JRB   Esko Tōnu T   Helgason Agnar A   Stefansson Kari K   Joshi Peter K PK   Kubo Michiaki M   Wilson James F JF  

Nature communications 20191031 1


In many species, the offspring of related parents suffer reduced reproductive success, a phenomenon known as inbreeding depression. In humans, the importance of this effect has remained unclear, partly because reproduction between close relatives is both rare and frequently associated with confounding social factors. Here, using genomic inbreeding coefficients (F<sub>ROH</sub>) for >1.4 million individuals, we show that F<sub>ROH</sub> is significantly associated (p < 0.0005) with apparently del  ...[more]

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