Associations of autozygosity with a broad range of human phenotypes

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 confoundi...

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Detalhes bibliográficos
Autores: Clark, DW; Okada, Y; Moore, KHS; Mason, D; Pirastu, N; Gandin, I; Mattsson, H; Barnes, CLK; Lin, K; Zhao, JH; Deelen, P; Rohde, R; Schurmann, C; Guo, XQ; Giulianini, F; Zhang, WH; Medina-Gomez, C; Karlsson, R; Bao, Y; Bartz, TM; Baumbach, C; Biino, G; Bixley, MJ; Brumat, M; Chai, JF; Corre, T; Cousminer, DL; Dekker, AM; Eccles, DA; Van Eijk, KR; Fuchsberger, C; Gao, H; Germain, M; Gordon, SD; de Haan, HG; Harris, SE; Hofer, E; Huerta-Chagoya, A; Igartua, C; Jansen, IE; Jia, YC; Kacprowski, T; Karlsson, T; Kleber, ME; Li, SA; Li-Gao, R; Mahajan, A; Matsuda, K; Meidtner, K; Meng, W; Montasser, ME; van der Most, PJ; Munz, M; Nutile, T; Palviainen, T; Prasad, G; Prasad, RB; Priyanka, TDS; Rizzi, F; Salvi, E; Sapkota, BR; Shriner, D; Skotte, L; Smart, MC; Smith, AV; van der Spek, A; Spracklen, CN; Strawbridge, RJ; Tajuddin, SM; Trompet, S; Turman, C; Verweij, N; Viberti, C; Wang, L; Warren, HR; Wootton, RE; Yanek, LR; Yao, J; Yousri, NA; Zhao, W; Adeyemo, AA; Afaq, S; Aguilar-Salinas, CA; Akiyama, M; Albert, ML; Allison, MA; Alver, M; Aung, T; Azizi, F; Bentley, AR; Boeing, H; Boerwinkle, E; Borja, JB; de Borst, GJ; Bottinger, EP; Broer, L; Campbell, H; Chanock, S; Chee, ML; Chen, G; Chen, YDI; Chen, ZM; Chiu, YF; Cocca, M; Collins, FS; Concas, MP; Corley, J; Cugliari, G; Van Dam, RM; Damulina, A; Daneshpour, MS; Day, FR; Delgado, GE; Dhana, K; Doney, ASF; Dorr, M; Doumatey, AP; Dzimiri, N; Ebenesersdottir, SS; Elliott, J; Elliott, P; Ewert, R; Felix, JF; Fischer, K; Freedman, BI; Girotto, G; Goel, A; Gogele, M; Goodarzi, MO; Graff, M; Granot-Hershkovitz, E; Grodstein, F; Guarrera, S; Gudbjartsson, DF; Guity, K; Gunnarsson, B; Guo, Y; Hagenaars, SP; Haiman, CA; Halevy, A; Harris, TB; Hedayati, M; van Heel, DA; Hirata, M; Hofer, I; Hsiung, CA; Huang, JY; Hung, YJ; Ikram, MA; Jagadeesan, A; Jousilahti, P; Kamatani, Y; Kanai, M; Kerrison, ND; Kessler, T; Khaw, KT; Khor, CC; de Kleijn, DPV; Koh, WP; Kolcic, I; Kraft, P; Kramer, BK; Kutalik, Z; Kuusisto, J; Langenberg, C; Launer, LJ; Lawlor, DA; Lee, IT; Lee, WJ; Lerch, MM; Li, LM; Liu, JJ; Loh, M; London, SJ; Loomis, S; Lu, YC; Luan, J; Magi, R; Manichaikul, AW; Manunta, P; Masson, G; Matoba, N; Mei, XW; Meisinger, C; Meitinger, T; Mezzavilla, M; Milani, L; Millwood, IY; Momozawa, Y; Moore, A; Morange, PE; Moreno-Macias, H; Mori, TA; Morrison, AC; Muka, T; Murakami, Y; Murray, AD; de Mutsert, R; Mychaleckyj, JC; Nalls, MA; Nauck, M; Neville, MJ; Nolte, IM; Ong, KK; Orozco, L; Padmanabhan, S; Palsson, G; Pankow, JS; Pattaro, C; Pattie, A; Polasek, O; Poulter, N; Pramstaller, PP; Quintana-Murci, L; Raikkonen, K; Ralhan, S; Rao, DC; van Rheenen, W; Rich, SS; Ridker, PM; Rietveld, CA; Robino, A; van Rooij, FJA; Ruggiero, D; Saba, Y; Sabanayagam, C; Sabater-Lleal, M; Sala, CF; Salomaa, V; Sandow, K; Schmidt, H; Scott, LJ; Scott, WR; Sedaghati-Khayat, B; Sennblad, B; van Setten, J; Sever, PJ; Sheu, WHH; Shi, Y; Shrestha, S; Shukla, SR; Sigurdsson, JK; Sikka, TT; Singh, JR; Smith, BH; Stancakova, A; Stanton, A; Starr, JM; Stefansdottir, L; Straker, L; Sulem, P; Sveinbjornsson, G; Swertz, MA; Taylor, AM; Taylor, KD; Terzikhan, N; Tham, YC; Thorleifsson, G; Thorsteinsdottir, U; Tillander, A; Tracy, RP; Tusie-Luna, T; Tzoulaki, I; Vaccargiu, S; Vangipurapu, J; Veldink, JH; Vitart, V; Volker, U; Vuoksimaa, E; Wakil, SM; Waldenberger, M; Wander, GS; Wang, YX; Wareham, NJ; Wild, S; Yajnik, CS; Yuan, JM; Zeng, LY; Zhang, L; Zhou, J; Amin, N; Asselbergs, FW; Bakker, SJL; Becker, DM; Lehne, B; Bennett, DA; den Berg, LH; Berndt, SI; Bharadwaj, D; Bielak, LF; Bochud, M; Boehnke, M; Bouchard, C; Bradfield, JP; Brody, JA; Campbell, A; Carmi, S; Caulfield, MJ; Cesarini, D; Chambers, JC; Chandak, GR; Cheng, CY; Ciullo, M; Cornelis, M; Cusi, D; Smith, GD; Deary, IJ; Dorajoo, R; van Duijn, CM; Ellinghaus, D; Erdmann, J; Eriksson, JG; Evangelou, E; Evans, MK; Faul, JD; Feenstra, B; Feitosa, M; Foisy, S; Franke, A; Friedlander, Y; Gasparini, P; Gieger, C; Gonzalez, C; Goyette, P; Grant, SFA; Griffiths, LR; Groop, L; Gudnason, V; Gyllensten, U; Hakonarson, H; Hamsten, A; van der Harst, P; Heng, CK; Hicks, AA; Hochner, H; Huikuri, H; Hunt, SC; Jaddoe, VWV; De Jager, PL; Johannesson, M; Johansson, A; Jonas, JB; Jukema, JW; Junttila, J; Kaprio, J; Kardia, SLR; Karpe, F; Kumari, M; Laakso, M; van der Laan, SW; Lahti, J; Laudes, M; Lea, RA; Lieb, W; Lumley, T; Martin, NG; Marz, W; Matullo, G; McCarthy, MI; Medland, SE; Merriman, TR; Metspalu, A; Meyer, BF; Mohlke, KL; Montgomery, GW; Mook-Kanamori, D; Munroe, PB; North, KE; Nyholt, DR; O'connell, JR; Ober, C; Oldehinkel, AJ; Palmas, W; Palmer, C; Pasterkamp, GG; Patin, E; Pennell, CE; Perusse, L; Peyser, PA; Pirastu, M; Polderman, TJC; Porteous, DJ; Posthuma, D; Psaty, BM; Rioux, JD; Rivadeneira, F; Rotimi, C; Rotter, JI; Rudan, I; Den Ruijter, HM; Sanghera, DK; Sattar, N; Schmidt, R; Schulze, MB; Schunkert, H; Scott, RA; Shuldiner, AR; Sim, X; Small, N; Smith, JA; Sotoodehnia, N; Tai, ES; Teumer, A; Timpson, NJ; Toniolo, D; Tregouet, DA; Tuomi, T; Vollenweider, P; Wang, CA; Weir, DR; Whitfield, JB; Wijmenga, C; Wong, TY; Wright, J; Yang, J; Yu, L; Zemel, BS; Zonderman, AB; Perola, M; Magnusson, PKE; Uitterlinden, AG; Kooner, JS; Chasman, DI; Loos, RJF; Franceschini, N; Franke, L; Haley, CS; Hayward, C; Walters, RG; Perry, JRB; Esko, T; Helgason, A; Stefansson, K; Joshi, PK; Kubo, M; Wilson, JF
Tipo de documento: Artigo
Estado:Published version
Data de publicação:2019
País:España
Recursos:Institut d’Investigació Biomèdica Sant Pau (IIB Sant Pau)
Repositório:r-IIB SANT PAU. Repositorio Institucional de Producción Científica del Instituto de Investigación Biomédica Sant Pau
OAI Identifier:oai:iibsantpau.fundanetsuite.com:p2299
Acesso em linha:https://iibsantpau.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=2299
Nível de acesso:Acesso aberto
Descrição
Resumo: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-ROH) for >1.4 million individuals, we show that F-ROH 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: F-ROH 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 F-ROH are confirmed within full-sibling pairs, where the variation in F-ROH is independent of all environmental confounding.