Associations of autozygosity with a broad range of human phenotypes

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المؤلفون: Clark, D.W.; Okada, Y.; Moore, K.H.S.; Mason, D.; Pirastu, N.; Gandin, I.; Mattsson, H.; Barnes, C.L.K.; Lin, K.; Zhao, J.H.; Deelan, P.; Rohde, R.; Schurmann, C.; Guo, X.; Giulianini, F.; Zhang, W.; Medina-Gomez, C.; Karlsson, R.; Bao, Y.; Bartz, T.M.; Baumbach, C.; Biino, G.; Bixley, M.J.; Brumat, M.; Chai, J.F.; Corre, T.; Cousminer, D.L.; Dekker, A.M.; Eccles, D.A.; van Eijk, K.R.; Fuchsberger, C.; Gao, H.; Germain, M.; Gordon, S.D.; de Haan, H.G.; Harris, S.E.; Hofer, E.; Huerta-Chagoya, A.; Igartua, C.; Jansen, I.E.; Jia, Y.; Kacprowski, T.; Karlsson, T.; Kleber, M.E.; Li, S.A.; Li-Gao, R.; Mahajan, A.L.; Matsuda, K.; Meidtner, K.; Meng, W.; Montasser, M.E.; van der Most, P.J.; Munz, M.; Nutile, T.; Palviainen, T.; Prasad, G.; Prasad, R.B.; Priyanka, T.D.S.; Rizzi, F.; Salvi, E.; Sapkota, B.R.; Shriner, D.; Skotte, L.; Smart, M.C.; Smith, A.V.; van der Spek, A.; Spracklen, C.N.; Strawbridge, R.J.; Tajuddin, S.M.; Trompet, S.; Turman, C.; Verweij, N.; Viberti, C.; Wang, L.; Warren, H.R.; Wootton, R.E.; Yanek, L.R.; Yao, J.; Yousri, N.A.; Zhao, W.; Adeyemo, A.A.; Albert, M.L.; Afaq, S.; Aguilar-Salinas, C.A.; Akiyama, M.; Allison, M.A.; Alver, M.; Aung, T.; Azizi, F.; Bentley, A.R.; Boeing, H.; Boerwinkle, E.; Borja, J.B.; de Borst, G.J.; Bottinger, E.P.; Broer, L.; Campbell, H.; Chanock, S.; Chee, M.L.; Chen, G.; Chen, Y.D.I.; Chen, Z.; Chiu, Y.-F.; Cocca, M.; Collins, F.S.; Concas, M.P.; Corley, J.; Cugliari, G.; van Dam, R.M.; Damulina, A.; Daneshpour, M.S.; Day, F.R.; Delgado, G.E.; Dhana, K.; Doney, A.F.S.; Dorr, M.; Doumatey, A.P.; Dzimiri, N.; Ebenesersdottir, S.S.; Elliott, J.; Elliott, P.; Ewert, R.; Felix, J.F.; Fischer, K.; Freedman, B.I.; Girotto, G.; Goel, A.; Gögele, M.; Goodarzi, M.O.; Graff, M.; Granot-Hershkovitz, E.; Grodstein, F.; Guarrera, S.; Gudbjartsson, D.F.; Guity, K.; Gunnarsson, B.; Guo, Y.; Hagenaars, S.P.; Haiman, C.A.; Halevy, A.; Harris, T.B.; Hedayati, M.; van Heel, D.a.; Hirata, M.; Höfer, I.; Hsiung, C.A.; Huang, J.; Hung, Y.-J.; Ikram, M.A.; Jagadeesan, A.; Jousilahti, P.; Kamatani, Y.; Kanai, M.; Kerrison, N.D.; Kessler, T.; Khaw, K.-T.; Khor, C.C.; de Kleijn, D.P.V.; Koh, W.-P.; Kolcic, I.; Kraft, P.; Krämer, B.K.; Kutalik, Z.; Kuusisto, J.; Langenberg, C.; Launer, L.J.; Lawlor, D.A.; Lee, I.-T.; Lee, W.-J.; Lerch, M.M.; Li, L.; Liu, J.; Loh, M.; London, S.J.; Loomis, S.; Lu, Y.; Luan, J.; Mägi, R.; Manichaikul, A.W.; Manunta, P.; Masson, G.; Matoba, N.; Mei, X.W.; Meisinger, C.; Meitinger, T.; Mezzavilla, M.; Milani, L.; Millwood, I.Y.; Momozawa, Y.; Moore, A.; Morange, P.-E.; Moreno-Macias, H.; Mori, T.A.; Morrison, A.C.; Muka, T.; Murakami, Y.; Murray, a.D.; de Mutsert, R.; Mychaleckyj, J.C.; Nalls, M.A.; Nauck, M.; Neville, M.J.; Nolte, I.M.; Ong, K.K.; Orozco, L.; Padmanabhan, S.; Palsson, G.; Pankow, J.S.; Pattaro, C.; Pattie, A.; Polasek, O.; Poulter, N.; Pramstaller, P.P.; Quintana-Murci, L; Räikkönen, K.; Ralhan, S.; Rao, D.C.; van Rheenen, W.; Rich, S.S.; Ridker, P.M.; Rietveld, C.A.; Robino, A.; van Rooij, F.J.A.; Ruggiero, D.; Saba, Y.; Sabanayagam, C.; Sabater-Lleal, M.; Sala, C.F.; Salomaa, V; Sandow, K.; Schmidt, H.; Scott, L.J.; Scott, W.R.; Sedaghati-Khayat, S.; Sennblad, B.; van Setter, J.; Sever, P.J.; Sheu, W.H.-H.; Shi, Y.; Shrestha, S.; Shukla, S.R.; Sigurdsson, J.K.; Sikka, T.T.; Singh, J.R.; Smith, B.H.; Stancakova, A; Stanton, A.; Starr, J.M.; Stefansdottir, L.; Straker, L.; Sulem, P.; Sveinbjornsson, G.; Swertz, M.A.; Taylor, A.M.; Taylor, K.D.; Terzikhan, N.; Tham, Y.-C.; Thorleifsson, G.; Thorsteinsdottir, U.; Tillander, A.; Tracy, R.P.; Tusie-Luna, T.; Tzoulaki, I.; Vaccargiu, S.; Vangipurapu, J.; Veldink, J.H.; Vitart V.; Völker, U.; Vuoksimaa, E.; Wakil, S.M.; Waldenberger, M.; Wander, G.S.; Wang, Y.X.; Wareham, N.J.; Wild, S.; Yajnik, C.S.; Yuan, J.-M.; Zeng, L.; Zhang, L.; Zhou, J.; Amin, N.; Asselbergs, F.W.; Bakker, S.J.L.; Becker, D.M.; Lehne, B.; Bennett, D.A.; van den Berg, L.H.; Berndt, S.I.; Bharadwaj, D.; Bielak, L.F.; Bochud, M.; Boehnke, M.; Bouchard, C.; Bradfield, J.P.; Brody, J.A.; Campbell, A.; Carmi, S.; Caulfield, M.J.; Cesarini, D.; Chambers, J.C.; Chandak, G.R.; Cheng, C.-Y.; Ciullo, M.; Cornelis, M.; Cusi, D.; Smith, G.D.; Deary, I.J.; Dorajoo, R.; van Duijn, C.M.; Ellinghaus, D.; Erdmann, J.; Eriksson, J.G.; Evangelou, E; Evans, M.K.; Faul, J.D.; Feenstra, B.; Feitosa, M.; Foisy, S.; Franke, A.; Friedlander, Y.; Gasparini, P.; Gieger, C.; Gonzalez, C.; Goyette, P.; Grant, S.F.A; Griffiths, L.; Groop, L.; Gudnason, V.; Gyllensten, U.; Hakonarson, H.; Hamsten, A.; van der Harst, P.; Heng, C.-K.; Hicks, A.A.; Hochner, H.; Huikuri, H.; Hunt, S.C.; Jaddoe, V.W.V.; De Jager, P.L.; Johannesson, M.; Johansson, Å.; Jonas, J.B.; Jukema, J.W.; Junttila, J.; Kaprio, J.; Kardia, S.L.R.; Karpe, F.; Kumari, M.; Laakso, M.; van der Laan, S.W.; Lahti, J.; Laudes, M.; Lea, R.A.; Lieb, W.; Lumley, T.; Martin, N.G.; März, W.; Matullo, G.; McCarthy, M.I.; Medland, S.E.; Merriman, T.R.; Metspalu, A.; Meyer, B.F.; Mohlke, K.L.; Montogomery, G.W.; Mook-Kanamori, D.; Munroe, P.B.; North, K.E.; Nyholt, D.R.; O’Connell, J.R.; Ober, C.; Oldehinkel, A.J.; Palmas, W.; Palmer, C.; Pasterkamp, G.G.; Patin, E.; Pennell, C.G.; Perusse, L.; Peyser, P.A.; Pirastu, M.; Polderman, T.J.C.; Porteous, D.J.; Posthuma, D.; Psaty, B.M.; Rioux, J.D.; Rivadeneira, F.; Rotimi, C.; Rotter, J.I.; Rudan, I; Den Ruijter, H.M.; Sanghera, D.K.; Sattar, N.; Schmidt, R.; Schulze, M.B.; Schunkert, H.; Scott, R.A.; Shuldiner, A.R.; Sim, X.; Small, Neil A.; Smith, J.A.; Sotoodehnia, N.; Tai, E.-S.; Teumer, A.; Timpson, N.J.; Toniolo, D.; Tregouet, D.-A.; Tuomi, T.; Vollenweider, P.; Wang, C.A.; Weir, D.R.; Whitfield, J.B.; Wijmenga C.; Wng, T.-Y.; Wright, J.; Yang, J.; Yu, L.; Zemel, B.S.; Zonderman, A.B.; Perola, M.; Magnusson, P.K.E.; Uitterlinden, A.G.; Kooner, J.S.; Chasman, D.I.; Loos, R.J.F.; Franceschini, N.; Franke, L.; Haley, C.S.; Hayward, C.; Walters, R.G.; Perry, J.R.B.; Esko, T.; Helgason, A.; Stefansson, K.; Joshi, P.K.; Kubo, M.; Wilson, J.F.
الموضوع:
Consanguinity; Genetic association study; Genetic markers; Inbreeding; Inbreeding depression
نوع التسجيلة:
article in journal/newspaper
اللغة:
English

معلومة اضافية
- الموضوع:
  2020
- Collection:
  Bradford Scholars@University of Bradford
- نبذة مختصرة :
  yes ; 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.
- Relation:
  Clark DW, Okada Y, Moore KHS, et al. (2019) Associations of autozygosity with a broad range of human phenotypes. Nature Communications. 10(1): 4957; http://hdl.handle.net/10454/18210; https://doi.org/10.1038/s41467-019-12283-6
- الرقم المعرف:
  10.1038/s41467-019-12283-6
- Rights:
  © 2019, The Author(s). This article is licensed under a Creative Commons Attribution 4.0 International License.
- الرقم المعرف:
  edsbas.3833515F

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Associations of autozygosity with a broad range of human phenotypes

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