University of Oulu

Clark, D.W., Okada, Y., Moore, K.H.S. et al. Associations of autozygosity with a broad range of human phenotypes. Nat Commun 10, 4957 (2019). https://doi.org/10.1038/s41467-019-12283-6

Associations of autozygosity with a broad range of human phenotypes

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Author: Clark, David W.1; Okada, Yukinori2,3,4; Moore, Kristjan H. S.5;
Mason, Dan6; Pirastu, Nicola1; Gandin, Ilaria7,8; Mattsson, Hannele9,10; Barnes, Catriona L. K.1; Lin, Kuang11; Zhao, Jing Hua12,13; Deelen, Patrick14; Rohde, Rebecca15; Schurmann, Claudia16; Guo, Xiuqing17; Giulianini, Franco18; Zhang, Weihua19,20; Medina-Gomez, Carolina21,22,23; Karlsson, Robert24; Bao, Yanchun25; Bartz, Traci M.26; Baumbach, Clemens27; Biino, Ginevra28; Bixley, Matthew J.29; Brumat, Marco8; Chai, Jin-Fang30; Corre, Tanguy31,32,33; Cousminer, Diana L.34,35; Dekker, Annelot M.36; Eccles, David A.37,38; Van Eijk, Kristel R.36; Fuchsberger, Christian39; Gao, He19,40; Germain, Marine41,42; Gordon, Scott D.43; de Haan, Hugoline G.44; Harris, Sarah E.45,46; Hofer, Edith47,48; Huerta-Chagoya, Alicia49; Igartua, Catherine50; Jansen, Iris E.51,52; Jia, Yucheng17; Kacprowski, Tim53,54; Karlsson, Torgny55; Kleber, Marcus E.56; Li, Shengchao Alfred57; Li-Gao, Ruifang44; Mahajan, Anubha58; Matsuda, Koichi59; Meidtner, Karina60,61; Meng, Weihua62,63; Montasser, May E.64,65; van der Most, Peter J.66; Munz, Matthias67,68,69,70,71,72,73,74; Nutile, Teresa75; Palviainen, Teemu76; Prasad, Gauri77; Prasad, Rashmi B.78; Priyanka, Tallapragada Divya Sri79; Rizzi, Federica80,81; Salvi, Erika81,82; Sapkota, Bishwa R.83; Shriner, Daniel84; Skotte, Line85; Smart, Melissa C.25; Smith, Albert Vernon86,87; van der Spek, Ashley22; Spracklen, Cassandra N.88; Strawbridge, Rona J.89,90; Tajuddin, Salman M.91; Trompet, Stella92,93; Turman, Constance94,95; Verweij, Niek96; Viberti, Clara97,98; Wang, Lihua99; Warren, Helen R.100,101; Wootton, Robyn E.102,103; Yanek, Lisa R.104; Yao, Jie17; Yousri, Noha A.105,106; Zhao, Wei107; Adeyemo, Adebowale A.84; Afaq, Saima19; Alberto Aguilar-Salinas, Carlos108,109; Akiyama, Masato3,110; Albert, Matthew L.111,112,113,114; Allison, Matthew A.115; Alver, Maris116; Aung, Tin117,118,119; Azizi, Fereidoun120; Bentley, Amy R.84; Boeing, Heiner121; Boerwinkle, Eric122; Borja, Judith B.123; de Borst, Gert J.124; Bottinger, Erwin P.16,125; Broer, Linda21; Campbell, Harry1; Chanock, Stephen126; Chee, Miao-Li117; Chen, Guanjie84; Chen, Yii-Der I.17; Chen, Zhengming11; Chiu, Yen-Feng127; Cocca, Massimiliano128; Collins, Francis S.129; Concas, Maria Pina128; Corley, Janie45,130; Cugliari, Giovanni97,98; Van Dam, Rob M.30,131,132; Damulina, Anna47; Daneshpour, Maryam S.133; Day, Felix R.12; Delgado, Graciela E.56; Dhana, Klodian22,132,134; Doney, Alexander S. F.135; Doerr, Marcus136,137; Doumatey, Ayo P.84; Dzimiri, Nduna138; Ebenesersdottir, S. Sunna5,139; Elliott, Joshua19; Elliott, Paul19,40,140,141,142,143; Ewert, Ralf136; Felix, Janine F.22,23,144; Fischer, Krista116; Freedman, Barry I.145; Girotto, Giorgia8,146; Goel, Anuj58,147; Gogele, Martin39; Goodarzi, Mark O.148; Graff, Mariaelisa15; Granot-Hershkovitz, Einat149; Grodstein, Francine94; Guarrera, Simonetta97,98; Gudbjartsson, Daniel F.5,150; Guity, Kamran133; Gunnarsson, Bjarni5; Guo, Yu151; Hagenaars, Saskia P.45,130,152; Haiman, Christopher A.153; Halevy, Avner149; Harris, Tamara B.91; Hedayati, Mehdi133; van Heel, David A.154; Hirata, Makoto155; Hofer, Imo156; Hsiung, Chao Agnes127; Huang, Jinyan157; Hung, Yi-Jen158,159; Ikram, M. Arfan22; Jagadeesan, Anuradha5,139; Jousilahti, Pekka160; Kamatani, Yoichiro3,161; Kanai, Masahiro2,3,162,163; Kerrison, Nicola D.12; Kessler, Thorsten; Khaw, Kay-Tee164; Khor, Chiea Chuen117,165; de Kleijn, Dominique P. V.124; Koh, Woon-Puay30,166; Kolcic, Ivana167; Kraft, Peter132; Kramer, Bernhard K.56; Kutalik, Zoltan32,33; Kuusisto, Johanna168,169; Langenberg, Claudia12; Launer, Lenore J.91; Lawlor, Deborah A.102,170,171; Lee, I-Te172,173,174; Lee, Wen-Jane175; Lerch, Markus M.176; Li, Liming177; Liu, Jianjun131,165; Loh, Marie19,178,179; London, Stephanie J.180; Loomis, Stephanie181; Lu, Yingchang16; Luan, Jian'an12; Magi, Reedik116; Manichaikul, Ani W.182; Manunta, Paolo183; Masson, Gisli5; Matoba, Nana3; Mei, Xue W.11; Meisinger, Christa184; Meitinger, Thomas185,186,187; Mezzavilla, Massimo146; Milani, Lili188; Millwood, Iona Y.11; Momozawa, Yukihide189; Moore, Amy126; Morange, Pierre-Emmanuel190,191; Moreno-Macias, Hortensia192; Mori, Trevor A.193; Morrison, Alanna C.194; Muka, Taulant22,195; Murakami, Yoshinori196; Murray, Alison D.197; de Mutsert, Renee44; Mychaleckyj, Josyf C.182; Nalls, Mike A.198,199; Nauck, Matthias137,200; Neville, Matt J.201,202; Nolte, Ilja M.66; Ong, Ken K.12,203; Orozco, Lorena204; Padmanabhan, Sandosh205; Palsson, Gunnar5; Pankow, James S.206; Pattaro, Cristian39; Pattie, Alison130; Polasek, Ozren167,207; Poulter, Neil208,209; Pramstaller, Peter P.39; Quintana-Murci, Lluis210,211,212; Raikkonen, Katri213; Ralhan, Sarju214,215; Rao, Dabeeru C.216; van Rheenen, Wouter36; Rich, Stephen S.182; Ridker, Paul M.18,217; Rietveld, Cornelius A.218,219; Robino, Antonietta128; van Rooij, Frank J. A.22; Ruggiero, Daniela75,220; Saba, Yasaman221; Sabanayagam, Charumathi117,118,119; Sabater-Lleal, Maria90,222; Felicita Sala, Cinzia223; Salomaa, Veikko224; Sandow, Kevin17; Schmidt, Helena221; Scott, Laura J.225,226; Scott, William R.19; Sedaghati-Khayat, Bahareh133; Sennblad, Bengt90,227; van Setten, Jessica228; Sever, Peter J.208; Sheu, Wayne H-H159,172,229,230; Shi, Yuan117; Shrestha, Smeeta79,231; Shukla, Sharvari Rahul232,233; Sigurdsson, Jon K.5; Sikka, Timo Tonis116; Singh, Jai Rup234; Smith, Blair H.235; Stancakova, Alena168; Stanton, Alice236; Starr, John M.45,237; Stefansdottir, Lilja5; Straker, Leon238; Sulem, Patrick5; Sveinbjornsson, Gardar5; Swertz, Morris A.14; Taylor, Adele M.130; Taylor, Kent D.17; Terzikhan, Natalie22,239; Tham, Yih-Chung117,118; Thorleifsson, Gudmar5; Thorsteinsdottir, Unnur5,87; Tillander, Annika24; Tracy, Russell P.240; Tusie-Luna, Teresa241,242; Tzoulaki, Ioanna19,40,243; Vaccargiu, Simona244; Vangipurapu, Jagadish168; Veldink, Jan H.36; Vitart, Veronique245; Volker, Uwe53,137; Vuoksimaa, Eero246; Wakil, Salma M.138; Waldenberger, Melanie27; Wander, Gurpreet S.247; Wang, Ya Xing248; Wareham, Nicholas J.12; Wild, Sarah249; Yajnik, Chittaranjan S.250; Yuan, Jian-Min251; Zeng, Lingyao; Zhang, Liang117; Zhou, Jie84; Amin, Najaf22; Asselbergs, Folkert W.252,253,254,255,256; Bakker, Stephan J. L.257; Becker, Diane M.104; Lehne, Benjamin19; Bennett, David A.258,259; van den Berg, Leonard H.36; Berndt, Sonja I.126; Bharadwaj, Dwaipayan260; Bielak, Lawrence F.107; Bochud, Murielle32; Boehnke, Mike225,226; Bouchard, Claude261; Bradfield, Jonathan P.262,263; Brody, Jennifer A.264; Campbell, Archie46; Carmi, Shai149; Caulfield, Mark J.100,101; Cesarini, David265,266; Chambers, John C.19,20,40,267,268; Chandak, Giriraj Ratan79; Cheng, Ching-Yu117,118,119; Ciullo, Marina75,220; Cornelis, Marilyn269; Cusi, Daniele81,270,271; Smith, George Davey102,171; Deary, Ian J.45,130; Dorajoo, Rajkumar165; van Duijn, Cornelia M.11,22; Ellinghaus, David272; Erdmann, Jeanette67; Eriksson, Johan G.273,274,275,276,277; Evangelou, Evangelos19,243; Evans, Michele K.91; Faul, Jessica D.278; Feenstra, Bjarke85; Feitosa, Mary99; Foisy, Sylvain279; Franke, Andre272; Friedlander, Yechiel149; Gasparini, Paolo8,146; Gieger, Christian27,61; Gonzalez, Clicerio280; Goyette, Philippe279; Grant, Struan F. A.35,262,281; Griffiths, Lyn R.37; Groop, Leif76,78; Gudnason, Vilmundur86,87; Gyllensten, Ulf55; Hakonarson, Hakon262,281; Hamsten, Anders282; van der Harst, Pim96; Heng, Chew-Kiat283,284; Hicks, Andrew A.39; Hochner, Hagit149; Huikuri, Heikki285,286; Hunt, Steven C.105,287; Jaddoe, Vincent W. V.22,23,144; De Jager, Philip L.288,289; Johannesson, Magnus290; Johansson, Asa55; Jonas, Jost B.248,291; Jukema, J. Wouter92; Junttila, Juhani285,286; Kaprio, Jaakko76,292; Kardia, Sharon L. R.107; Karpe, Fredrik201,293; Kumari, Meena25; Laakso, Markku168,169; van der Laan, Sander W.156; Lahti, Jari213,294; Laudes, Matthias295; Lea, Rodney A.37; Lieb, Wolfgang296,297; Lumley, Thomas298; Martin, Nicholas G.43; Marz, Winfried56,299,300; Matullo, Giuseppe97,98; McCarthy, Mark I.58,201,293; Medland, Sarah E.43; Merriman, Tony R.29; Metspalu, Andres116; Meyer, Brian F.301; Mohlke, Karen L.88; Montgomery, Grant W.43,302; Mook-Kanamori, Dennis44,303; Munroe, Patricia B.100,101; North, Kari E.15; Nyholt, Dale R.43,304; O'connell, Jeffery R.64,65; Ober, Carole50; Oldehinkel, Albertine J.305; Palmas, Walter306; Palmer, Colin307; Pasterkamp, Gerard G.156; Patin, Etienne210,211,212; Pennell, Craig E.308,309; Perusse, Louis310,311; Peyser, Patricia A.107; Pirastu, Mario312; Polderman, Tinca J. C.51; Porteous, David J.45,46; Posthuma, Danielle51,313; Psaty, Bruce M.314,315,316,317; Rioux, John D.279,318; Rivadeneira, Fernando21,22,23; Rotimi, Charles84; Rotter, Jerome I.17; Rudan, Igor1; Den Ruijter, Hester M.319; Sanghera, Dharambir K.83,320; Sattar, Naveed205; Schmidt, Reinhold47; Schulze, Matthias B.60,61,321; Schunkert, Heribert322; Scott, Robert A.12; Shuldiner, Alan R.64,65,323; Sim, Xueling30; Small, Neil324; Smith, Jennifer A.107,278; Sotoodehnia, Nona325; Tai, E-Shyong30,131,326; Teumer, Alexander137,327; Timpson, Nicholas J.102,328,329; Toniolo, Daniela223; Tregouet, David-Alexandre41; Tuomi, Tiinamaija10,330,276,331; Vollenweider, Peter332; Wang, Carol A.308,309; Weir, David R.278; Whitfield, John B.43; Wijmenga, Cisca14; Wong, Tien-Yin117,118; Wright, John6; Yang, Jingyun258,259; Yu, Lei258,259; Zemel, Babette S.281,333; Zonderman, Alan B.91; Perola, Markus334; Magnusson, Patrik K. E.24; Uitterlinden, Andre G.21,22,23; Kooner, Jaspal S.20,40,268,335; Chasman, Daniel I.18,217; Loos, Ruth J. F.16,336; Franceschini, Nora15; Franke, Lude14; Haley, Chris S.245,337,338; Hayward, Caroline245; Walters, Robin G.11; Perry, John R. B.12; Esko, Tonu116,339; Helgason, Agnar5,139; Stefansson, Kari5,87; Joshi, Peter K.1; Kubo, Michiaki189; Wilson, James F.1,245
Organizations: 1Univ Edinburgh, Usher Inst, Ctr Global Hlth Res, Edinburgh EH8 9AG, Midlothian, Scotland.
2Osaka Univ, Dept Stat Genet, Grad Sch Med, Suita, Osaka 5650871, Japan.
3RIKEN, Lab Stat Anal, Ctr Integrat Med Sci, Yokohama, Kanagawa 2300045, Japan.
4Osaka Univ, Immunol Frontier Res Ctr WPI IFReC, Lab Stat Immunol, Suita, Osaka 5650871, Japan.
5Amgen Inc, DeCODE Genet, IS-101 Reykjavik, Iceland.
6Bradford Teaching Hosp NHS Trust, Bradford Inst Hlth Res, Bradford BD9 6RJ, W Yorkshire, England.
7Area Sci Pk, Res Unit, I-34149 Trieste, Italy.
8Univ Trieste, Dept Med Surg & Hlth Sci, Trieste, Italy.
9Natl Inst Hlth & Welf, Unit Publ Hlth Solut, Helsinki, Finland.
10Univ Helsinki, Inst Mol Med Finland, Helsinki, Finland.
11Univ Oxford, Nuffield Dept Populat Hlth, Oxford OX3 7LF, England.
12Univ Cambridge, Sch Clin Med, MRC Epidemiol Unit, Cambridge CB2 0QQ, England.
13Univ Cambridge, Dept Publ Hlth & Primary Care, Cardiovasc Epidemiol Unit, Cambridge CB1 8RN, England.
14Univ Groningen, Univ Med Ctr Groningen, Dept Genet, NL-9700 RB Groningen, Netherlands.
15Univ N Carolina, Gillings Sch Global Publ Hlth, Dept Epidemiol, Chapel Hill, NC 27514 USA.
16Ichan Sch Med Mt Sinai, Charles Bronfman Inst Personalized Med, New York, NY 10029 USA.
17Harbor UCLA Med Ctr, Inst Translat Genom & Populat Sci, LABioMed, Div Genom Outcomes,Dept Pediat, Torrance, CA 90502 USA.
18Brigham & Womens Hosp, Div Prevent Med, Boston, MA 02215 USA.
19Imperial Coll London, Dept Epidemiol & Biostat, London W2 1PG, England.
20Ealing Gen Hosp, Dept Cardiol, Middlesex UB1 3HW, England.
21Erasmus MC, Dept Internal Med, NL-3015 CN Rotterdam, Netherlands.
22Erasmus MC, Dept Epidemiol, NL-3015 CN Rotterdam, Netherlands.
23Erasmus MC, Generat R Study Grp, NL-3015 CN Rotterdam, Netherlands.
24Karolinska Inst, Dept Med Epidemiol & Biostat, S-17177 Stockholm, Sweden.
25Univ Essex, Inst Social & Econ Res, Colchester CO4 3SQ, Essex, England.
26Univ Washington, Dept Biostat & Med, Cardiovasc Hlth Res Unit, Seattle, WA 98101 USA.
27German Res Ctr Environm Hlth, Helmholtz Zentrum Munchen, Inst Epidemiol, Res Unit Mol Epidemiol, D-85764 Neuherberg, Germany.
28Natl Res Council Italy, Inst Mol Genet, I-27100 Pavia, Italy.
29Univ Otago, Dept Biochem, Dunedin 9054, New Zealand.
30Natl Univ Singapore, Saw Swee Hock Sch Publ Hlth, Singapore 117549, Singapore.
31Univ Lausanne, Dept Computat Biol, CH-1011 Lausanne, Switzerland.
32Univ Lausanne, Ctr Primary Care & Publ Hlth Unisante, Lausanne, Switzerland.
33Swiss Inst Bioinformat, CH-1015 Lausanne, Switzerland.
34Childrens Hosp Philadelphia, Div Human Genet, Philadelphia, PA 19104 USA.
35Univ Penn, Perelman Sch Med, Dept Genet, Philadelphia, PA 19104 USA.
36Univ Utrecht, Univ Med Ctr Utrecht, Brain Ctr Rudolf Magnus, Dept Neurol, NL-3584 CX Utrecht, Netherlands.
37Queensland Univ Technol, Inst Hlth & Biomed Innovat, Sch Biomed Sci, Genom Res Ctr, Brisbane, Qld 4059, Australia.
38Malaghan Inst Med Res, Wellington 6242, New Zealand.
39Univ Lubeck, Affiliated Inst, Inst Biomed, Eurac Res, I-39100 Bolzano, Italy.
40Imperial Coll London, MRC PHE Ctr Environm & Hlth, London W2 1PG, England.
41Sorbonne Univ, INSERM, UMR S 1166, F-75013 Paris, France.
42ICAN Inst Cardiometab & Nutr, F-75013 Paris, France.
43QIMR Berghofer Inst Med Res, Brisbane, Qld, Australia.
44Leiden Univ, Dept Clin Epidemiol, Med Ctr, NL-2333 ZA Leiden, Netherlands.
45Univ Edinburgh, Ctr Cognit Ageing & Cognit Epidemiol, Edinburgh EH8 9JZ, Midlothian, Scotland.
46Univ Edinburgh, Inst Genet & Mol Med, Ctr Genom & Expt Med, Edinburgh EH4 2XU, Midlothian, Scotland.
47Med Univ Graz, Clin Div Neurogeriatr, Dept Neurol, A-8036 Graz, Austria.
48Med Univ Graz, Inst Med Informat Stat & Documentat, A-8036 Graz, Austria.
49CONACyT, Inst Nacl Ciencias Med & Nutr Salvador Zubiran, Mexico City 03940, DF, Mexico.
50Univ Chicago, Dept Human Genet, Chicago, IL 60637 USA.
51Vrije Univ Amsterdam, Ctr Neurogenom & Cognit Res, Dept Complex Trait Genet, NL-1081 HV Amsterdam, Netherlands.
52Vrije Univ Amsterdam Med Ctr, Alzheimer Ctr, Dept Neurol, Amsterdam Neurosci, NL-1081 HV Amsterdam, Netherlands.
53Univ Med Greifswald, Interfaculty Inst Genet & Funct Genom, D-17475 Greifswald, Germany.
54Tech Univ Munich, TUM Sch Life Sci Weihenstephan, Chair Expt Bioinformat, D-85354 Freising Weihenstephan, Germany.
55Uppsala Univ, Sci Life Lab, Dept Immunol Genet & Pathol, S-75108 Uppsala, Sweden.
56Heidelberg Univ, Med Fac Mannheim, Dept Med 5, Nephrol,Hypertensiol,Rheumatol,Endocrinol,Diabeto, D-68167 Mannheim, Germany.
57Leidos Biomed Res Inc, Frederick Natl Lab Canc Res, Canc Genom Res Lab, Frederick, MD USA.
58Univ Oxford, Wellcome Ctr Human Genet, Oxford OX3 7BN, England.
59Univ Tokyo, Grad Sch Frontier Sci, Dept Computat Biol & Med Sci, Tokyo 1088639, Japan.
60German Inst Human Nutr Potsdam Rehbrucke, Dept Mol Epidemiol, Nuthetal, Germany.
61German Ctr Diabet Res DZD, Munich, Germany.
62Univ Dundee, Ninewells Hosp, Med Res Inst, Dundee, Scotland.
63Univ Dundee, Sch Med, Dundee, Scotland.
64Univ Maryland, Sch Med, Dept Med, Div Endocrinol Diabet & Nutr, Baltimore, MD 21201 USA.
65Univ Maryland, Sch Med, Dept Med, Program Personalized & Genom Med, Baltimore, MD 21201 USA.
66Univ Groningen, Univ Med Ctr Groningen, Dept Epidemiol, NL-9700 RB Groningen, Netherlands.
67Univ Lubeck, Inst Cardiogenet, D-23562 Lubeck, Germany.
68DZHK German Res Ctr Cardiovasc Res, Partner Site Hamburg Lubeck Kiel, D-23562 Lubeck, Germany.
69Univ Heart Ctr Luebeck, D-23562 Lubeck, Germany.
70Charite Univ Med Berlin, Berlin, Germany.
71Free Univ Berlin, Berlin, Germany.
72Humboldt Univ, Berlin, Germany.
73Berlin Inst Hlth, Berlin, Germany.
74Inst Dent & Craniofacial Sci, Dept Periodontol & Synopt Dent, Berlin, Germany.
75CNR, Inst Genet & Biophys A Buzzati Traverso, I-80131 Naples, Italy.
76Univ Helsinki, Finnish Inst Mol Med, Helsinki, Finland.
77CSIR Inst Genom & Integrat Biol, Genom & Mol Med Unit, New Delhi 110020, India.
78Lund Univ, Skane Univ Hosp, Diabet Ctr, Dept Clin Sci Diabet & Endocrinol, S-20502 Malmo, Sweden.
79CSIR Ctr Cellular & Mol Biol, Genom Res Complex Dis GRC Grp, Hyderabad 500007, Telangana, India.
80EPhood SRL, EPhood Sci Unit, I-20091 Milan, Italy.
81Univ Milan, Dept Hlth Sci, I-20139 Milan, Italy.
82IRCCS Fdn Carlo Besta Neurol Inst, Neuroalgol Unit, I-20133 Milan, Italy.
83Univ Oklahoma, Hlth Sci Ctr, Coll Med, Dept Pediat, Oklahoma City, OK 73104 USA.
84NHGRI, Ctr Res Genom & Global Hlth, NIH, Bethesda, MD 20892 USA.
85Statens Serum Inst, Dept Epidemiol Res, DK-2300 Copenhagen, Denmark.
86Iceland Heart Assoc, IS-201 Kopavogur, Iceland.
87Univ Iceland, Sch Hlth Sci, Fac Med, IS-101 Reykjavik, Iceland.
88Univ N Carolina, Dept Genet, Chapel Hill, NC 27599 USA.
89Univ Glasgow, Inst Hlth & Wellbeing, Glasgow G12 8RZ, Lanark, Scotland.
90Karolinska Inst, Ctr Mol Med, Dept Med Solna, Cardiovasc Med Unit, S-17176 Stockholm, Sweden.
91NIA, Lab Epidemiol & Populat Sci, NIH, Baltimore, MD 21224 USA.
92Leiden Univ, Med Ctr, Dept Cardiol, NL-2300 RC Leiden, Netherlands.
93Leiden Univ, Med Ctr, Dept Internal Med, Sect Gerontol & Geriatr, NL-2300 RC Leiden, Netherlands.
94Harvard TH Chan Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA.
95Harvard TH Chan Sch Publ Hlth, Program Genet Epidemiol & Stat Genet, Boston, MA 02115 USA.
96Univ Groningen, Univ Med Ctr Groningen, Dept Cardiol, NL-9713 GZ Groningen, Netherlands.
97Univ Turin, IIGM, I-10126 Turin, Italy.
98Univ Turin, Dept Med Sci, I-10126 Turin, Italy.
99Washington Univ, Sch Med, Dept Genet, Div Stat Genom, St Louis, MO 63110 USA.
100Queen Mary Univ London, Barts & London Sch Med & Dent, NIHR Barts Cardiovasc Biomed Res Ctr, London EC1M 6BQ, England.
101Queen Mary Univ London, William Harvey Res Inst, Barts & London Sch Med & Dent, Dept Clin Pharmacol, London EC1M 6BQ, England.
102Univ Bristol, MRC Integrat Epidemiol Unit, Bristol BS8 2BN, Avon, England.
103Univ Bristol, Sch Psychol Sci, Bristol BS8 1TU, Avon, England.
104Johns Hopkins Univ, Sch Med, GeneSTAR Res Program, Dept Med, Baltimore, MD 21287 USA.
105Weill Cornell Med Qatar, Dept Genet Med, Doha, Qatar.
106Alexandria Univ, Comp & Syst Engn, Alexandria, Egypt.
107Univ Michigan, Sch Publ Hlth, Dept Epidemiol, Ann Arbor, MI 48109 USA.
108Inst Nacl Ciencias Med & Nutr Salvador Zubiran, Dept Endocrinol & Metab, Mexico City 14080, DF, Mexico.
109Escuela Med & Ciencias Salud, Tecnol Monterrey, Unidad Invest Enfermades Metabol, Monterrey 64710, NL, Mexico.
110Kyushu Univ, Grad Sch Med Sci, Dept Ophthalmol, Fukuoka, Fukuoka 8128582, Japan.
111Inst Pasteur, Immunobiol Dendrit Cells, F-75015 Paris, France.
112INSERM, U1223, F-75015 Paris, France.
113Inst Pasteur, Ctr Translat Res, F-75015 Paris, France.
114Genentech Inc, Dept Canc Immunol, San Francisco, CA 94080 USA.
115UC San Diego Sch Med, Dept Family Med & Publ Hlth, Div Prevent Med, La Jolla, CA 92093 USA.
116Univ Tartu, Estonian Genome Ctr, EE-51010 Tartu, Estonia.
117Singapore Natl Eye Ctr, Singapore Eye Res Inst, Singapore 169856, Singapore.
118Duke NUS Med Sch, Ophthalmol & Visual Sci Acad Clin Program Eye ACP, Singapore 169857, Singapore.
119Natl Univ Singapore, Yong Loo Lin Sch Med, Dept Ophthalmol, Singapore 119228, Singapore.
120Shahid Beheshti Univ Med Sci, Res Inst Endocrine Sci, Endocrine Res Ctr, Tehran 1983963113, Iran.
121German Inst Human Nutr Potsdam Rehbrucke, Dept Epidemiol, Nuthetal, Germany.
122Univ Texas Houston, UTHlth Sch Publ Hlth, Hlth Sci Ctr Houston, Houston, TX 77030 USA.
123Univ San Carlos, USC Off Populat Studies Fdn Inc, Dept Nutr & Dietet, Cebu 6000, Cebu, Philippines.
124Univ Utrecht, Univ Med Ctr Utrecht, Div Surg Specialties, Dept Vasc Surg, NL-3584 CX Utrecht, Netherlands.
125Univ Potsdam, Hasso Plattner Inst, Digital Hlth Ctr, D-14482 Potsdam, Germany.
126NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA.
127Natl Hlth Res Inst, Inst Populat Hlth Sci, Miaoli, Taiwan.
128IRCCS Burlo Garofolo, Inst Maternal & Child Hlth, I-34137 Trieste, Italy.
129NHGRI, NIH, Bethesda, MD 20892 USA.
130Univ Edinburgh, Dept Psychol, 7 George Sq, Edinburgh EH8 9JZ, Midlothian, Scotland.
131Natl Univ Singapore, Yong Loo Lin Sch Med, Dept Med, Singapore 119228, Singapore.
132Harvard T H Chan Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA.
133Shahid Beheshti Univ Med Sci, Res Inst Endocrine Sci, Cellular & Mol Endocrine Res Ctr, Tehran 1983963113, Iran.
134Rush Univ, Med Ctr, Dept Internal Med, Chicago, IL 60612 USA.
135Univ Dundee, MEMO Res Mol & Clin Med, Dundee DD1 9SY, Scotland.
136Univ Med Greifswald, Dept Internal Med B, D-17475 Greifswald, Germany.
137DZHK German Ctr Cardiovasc Res, Partner Site Greifswald, D-17475 Greifswald, Germany.
138King Faisal Specialist Hosp & Res Ctr, Dept Genet, Riyadh 12713, Saudi Arabia.
139Univ Iceland, Dept Anthropol, IS-101 Reykjavik, Iceland.
140Imperial Coll Healthcare NHS Trust, Imperial Biomed Res Ctr, Natl Inst Hlth Res, London, England.
141Imperial Coll London, London, England.
142Imperial Coll London, UK DRI, London, England.
143Hlth Data Res UK London, London, England.
144Erasmus MC, Dept Pediat, NL-3015 CN Rotterdam, Netherlands.
145Wake Forest Sch Med, Dept Internal Med, Sect Nephrol, Winston Salem, NC 27101 USA.
146IRCCS Burlo Garofolo, Inst Maternal & Child Hlth, Med Genet, Trieste, Italy.
147Univ Oxford, Radcliffe Dept Med, Div Cardiovasc Med, Oxford OX3 9DU, England.
148Cedars Sinai Med Ctr, Dept Med, Div Endocrinol Diabet & Metab, Los Angeles, CA 90048 USA.
149Hebrew Univ Jerusalem, Hadassah Med Ctr, Braun Sch Publ Hlth, Jerusalem, Israel.
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Format: article
Version: published version
Access: open
Online Access: PDF Full Text (PDF, 5.3 MB)
Persistent link: http://urn.fi/urn:nbn:fi-fe2020042822782
Language: English
Published: Springer Nature, 2019
Publish Date: 2020-04-28
Description:

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 < 0.0005) with apparently deleterious changes in 32 out of 100 traits analysed. These changes are associated with runs of homozygosity (ROH), but not with common variant homozygosity, suggesting that genetic variants associated with inbreeding depression are predominantly rare. The effect on fertility is striking: FROH equivalent to the offspring of first cousins is associated with a 55% decrease [95% CI 44–66%] in the odds of having children. Finally, the effects of FROH are confirmed within full-sibling pairs, where the variation in FROH is independent of all environmental confounding.

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Series: Nature communications
ISSN: 2041-1723
ISSN-E: 2041-1723
ISSN-L: 2041-1723
Volume: 10
Article number: 4957
DOI: 10.1038/s41467-019-12283-6
OADOI: https://oadoi.org/10.1038/s41467-019-12283-6
Type of Publication: A1 Journal article – refereed
Field of Science: 3111 Biomedicine
Subjects:
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