Associations of autozygosity with a broad range of human phenotypes
journal contribution
posted on 2025-05-09, 01:38 authored by David W. Clark, 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 Doerr, AP Doumatey, N Dzimiri, SS Ebenesersdottir, J Elliott, P Elliott, R Ewert, JF Felix, K Fischer, BI Freedman, G Girotto, A Goel, M Gogele, 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 Hofer, CA Hsiung, J Huang, Y-J Hung, MA Ikram, A Jagadeesan, P Jousilahti, Y Kamatani, M Kanai, ND Kerrison, T Kessler, K-T Khaw, CC Khor, DPV de Kleijn, W-P Koh, I Kolcic, P Kraft, BK Kramer, Z Kutalik, J Kuusisto, C Langenberg, LJ Launer, DA Lawlor, I-T Lee, W-J Lee, MM Lerch, L Li, J Liu, M Loh, SJ London, S Loomis, Y Lu, J Luan, R Magi, AW Manichaikul, P Manunta, G Masson, N Matoba, XW Mei, C Meisinger, T Meitinger, M Mezzavilla, L Milani, IY Millwood, Y Momozawa, A Moore, P-E Morange, H Moreno-Macias, 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 Palsson, JS Pankow, C Pattaro, A Pattie, O Polasek, N Poulter, PP Pramstaller, L Quintana-Murci, K Raikkonen, 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, C Felicita Sala, V Salomaa, K Sandow, H Schmidt, LJ Scott, WR Scott, B Sedaghati-Khayat, B Sennblad, J van Setten, PJ Sever, WH-H Sheu, Y Shi, S Shrestha, SR Shukla, JK Sigurdsson, TT Sikka, JR Singh, BH Smith, A Stancakova, A Stanton, JM Starr, L Stefansdottir, L Straker, P Sulem, G Sveinbjornsson, MA Swertz, AM Taylor, KD Taylor, N Terzikhan, Y-C Tham, G Thorleifsson, U Thorsteinsdottir, A Tillander, RP Tracy, T Tusie-Luna, I Tzoulaki, S Vaccargiu, J Vangipurapu, JH Veldink, V Vitart, U Volker, E Vuoksimaa, SM Wakil, M Waldenberger, GS Wander, YX Wang, NJ Wareham, S Wild, CS Yajnik, J-M 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, C-Y 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, C-K Heng, AA Hicks, H Hochner, H Huikuri, SC Hunt, VWV Jaddoe, PL De Jager, M Johannesson, A 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, Rodney LeaRodney Lea, W Lieb, T Lumley, NG Martin, W Marz, 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, Craig PennellCraig 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, E-S Tai, A Teumer, NJ Timpson, D Toniolo, D-A Tregouet, T Tuomi, P Vollenweider, Aiyun WangAiyun Wang, DR Weir, JB Whitfield, C Wijmenga, T-Y 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, Yukinori Okada, Patrick Deelen, Lorena Orozco, Rebecca Rohde, Claudia Schurmann, Xiuqing Guo, Franco Giulianini, Weihua Zhang, Carolina Medina-Gomez, Robert Karlsson, Yanchun Bao, Traci M. Bartz, Kristjan H. S. Moore, Clemens Baumbach, G Biino, MJ Bixley, M Brumat, J-F Chai, T Corre, DL Cousminer, AM Dekker, DA Eccles, KR Van Eijk, Dan Mason, C Fuchsberger, H Gao, M Germain, SD Gordon, HG de Haan, SE Harris, E Hofer, A Huerta-Chagoya, C Igartua, IE Jansen, Nicola Pirastu, Y Jia, T Kacprowski, T Karlsson, ME Kleber, SA Li, R Li-Gao, A Mahajan, K Matsuda, K Meidtner, W Meng, Ilaria Gandin, ME Montasser, PJ van der Most, M Munz, T Nutile, T Palviainen, G Prasad, RB Prasad, TDS Priyanka, F Rizzi, E Salvi, Hannele Mattsson, BR Sapkota, D Shriner, L Skotte, MC Smart, AV Smith, A van der Spek, CN Spracklen, RJ Strawbridge, SM Tajuddin, S Trompet, Catriona L. K. Barnes, C Turman, N Verweij, C Viberti, L Wang, HR Warren, RE Wootton, LR Yanek, J Yao, NA Yousri, W Zhao, Kuang Lin, AA Adeyemo, S Afaq, C Alberto Aguilar-Salinas, M Akiyama, ML Albert, MA Allison, M Alver, T Aung, F Azizi, AR Bentley, Jing Hua Zhao, H Boeing, E Boerwinkle, JB Borja, GJ de Borst, EP Bottinger, L Broer, H Campbell, S Chanock, M-L Chee, G ChenIn 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.
History
Journal title
Nature CommunicationsVolume
10Publisher
Nature Publishing GroupLanguage
- en, English
