Title | Associations of autozygosity with a broad range of human phenotypes. |
Publication Type | Journal Article |
Year of Publication | 2019 |
Authors | 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, X, Giulianini, F, Zhang, W, Medina-Gómez, C, Karlsson, R, Bao, Y, Bartz, TM, Baumbach, C, Biino, G, Bixley, MJ, Brumat, M, Chai, J-F, 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, Y, Kacprowski, T, Karlsson, T, Kleber, ME, Li, SAlfred, 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, TDivya Sri, Rizzi, F, Salvi, E, Sapkota, BR, Shriner, D, Skotte, L, Smart, MC, Smith, AVernon, 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, CAlberto, 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, M-L, Chen, G, Chen, Y-derI, Chen, Z, Chiu, Y-F, Cocca, M, Collins, FS, Concas, MPina, Corley, J, Cugliari, G, van Dam, RM, Damulina, A, Daneshpour, MS, Day, FR, Delgado, GE, Dhana, K, Doney, ASF, Dörr, M, Doumatey, AP, Dzimiri, N, S Ebenesersdóttir, S, Elliott, J, Elliott, P, Ewert, R, Felix, JF, Fischer, K, Freedman, BI, Girotto, G, Goel, A, Gögele, 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, Höfer, I, Hsiung, CAgnes, Huang, J, Hung, Y-J, Ikram, AM, Jagadeesan, A, Jousilahti, P, Kamatani, Y, Kanai, M, Kerrison, ND, Kessler, T, Khaw, K-T, Khor, CChuen, de Kleijn, DPV, Koh, W-P, Kolcic, I, Kraft, P, Krämer, BK, Kutalik, Z, Kuusisto, J, Langenberg, C, Launer, LJ, Lawlor, DA, Lee, I-T, Lee, W-J, Lerch, MM, Li, L, Liu, J, Loh, M, London, SJ, Loomis, S, Lu, Y, Luan, J'an, Mägi, R, Manichaikul, AW, Manunta, P, Másson, G, Matoba, N, Mei, XW, Meisinger, C, Meitinger, T, Mezzavilla, M, Milani, L, Millwood, IY, Momozawa, Y, Moore, A, Morange, P-E, 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, Pálsson, G, Pankow, JS, Pattaro, C, Pattie, A, Polasek, O, Poulter, N, Pramstaller, PP, Quintana-Murci, L, Räikkönen, 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, CFelicita, Salomaa, V, Sandow, K, Schmidt, H, Scott, LJ, Scott, WR, Sedaghati-Khayat, B, Sennblad, B, van Setten, J, Sever, PJ, Sheu, WH-H, Shi, Y, Shrestha, S, Shukla, SRahul, Sigurdsson, JK, Sikka, TTonis, Singh, JRup, Smith, BH, Stančáková, A, Stanton, A, Starr, JM, Stefansdottir, L, Straker, L, Sulem, P, Sveinbjornsson, G, Swertz, MA, Taylor, AM, Taylor, KD, Terzikhan, N, Tham, Y-C, Thorleifsson, G, Thorsteinsdottir, U, Tillander, A, Tracy, RP, Tusié-Luna, T, Tzoulaki, I, Vaccargiu, S, Vangipurapu, J, Veldink, JH, Vitart, V, Völker, U, Vuoksimaa, E, Wakil, SM, Waldenberger, M, Wander, GS, Wang, YXing, Wareham, NJ, Wild, S, Yajnik, CS, Yuan, J-M, Zeng, L, Zhang, L, Zhou, J, Amin, N, Asselbergs, FW, Bakker, SJL, Becker, DM, Lehne, B, Bennett, DA, van 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, GRatan, Cheng, C-Y, 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, C-K, Hicks, AA, Hochner, H, Huikuri, H, Hunt, SC, Jaddoe, VWV, De Jager, PL, Johannesson, M, Johansson, A, Jonas, JB, J Jukema, W, 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, März, 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, Ruijter, HM den, Sanghera, DK, Sattar, N, Schmidt, R, Schulze, MB, Schunkert, H, Scott, RA, Shuldiner, AR, Sim, X, Small, N, Smith, JA, Sotoodehnia, N, Tai, E-S, Teumer, A, Timpson, NJ, Toniolo, D, Trégouët, D-A, Tuomi, T, Vollenweider, P, Wang, CA, Weir, DR, Whitfield, JB, Wijmenga, C, Wong, T-Y, 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 |
Journal | Nat Commun |
Volume | 10 |
Issue | 1 |
Pagination | 4957 |
Date Published | 2019 Oct 31 |
ISSN | 2041-1723 |
Abstract | <p>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) for >1.4 million individuals, we show that F 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 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 are confirmed within full-sibling pairs, where the variation in F is independent of all environmental confounding.</p> |
DOI | 10.1038/s41467-019-12283-6 |
Alternate Journal | Nat Commun |
PubMed ID | 31673082 |
PubMed Central ID | PMC6823371 |