Associations of autozygosity with a broad range of human phenotypes: Nature Communications

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

Research output: Contribution to journalArticle

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. © 2019, The Author(s).
Original languageEnglish
JournalNature Communications
Volume10
DOIs
Publication statusPublished - 2019

Fingerprint Dive into the research topics of 'Associations of autozygosity with a broad range of human phenotypes: Nature Communications'. Together they form a unique fingerprint.

  • Cite this

    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-Gomez, C., Karlsson, R., Bao, Y., ... Wilson, JF. (2019). Associations of autozygosity with a broad range of human phenotypes: Nature Communications. Nature Communications, 10. https://doi.org/10.1038/s41467-019-12283-6