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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Main Authors:	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., Deelen, 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., 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., Afaq, S., Aguilar-Salinas, C.A., Akiyama, M., Albert, M.L., 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.
Format:	Journal Article
Language:	English
Published:	NATURE PUBLISHING GROUP 2019
Subjects:	Science & Technology Multidisciplinary Sciences Science & Technology - Other Topics INBREEDING DEPRESSION HOMOZYGOSITY FERTILITY LOCI RUNS QUANTIFICATION
Online Access:	http://hdl.handle.net/20.500.11937/79988

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author	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. Deelen, 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. 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. Afaq, S. Aguilar-Salinas, C.A. Akiyama, M. Albert, M.L. 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.
author_facet	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. Deelen, 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. 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. Afaq, S. Aguilar-Salinas, C.A. Akiyama, M. Albert, M.L. 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.
author_sort	Clark, D.W.
building	Curtin Institutional Repository
collection	Online Access
description	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.
first_indexed	2025-11-14T11:14:35Z
format	Journal Article
id	curtin-20.500.11937-79988
institution	Curtin University Malaysia
institution_category	Local University
language	English
last_indexed	2025-11-14T11:14:35Z
publishDate	2019
publisher	NATURE PUBLISHING GROUP
recordtype	eprints
repository_type	Digital Repository
spelling	curtin-20.500.11937-799882021-01-08T07:54:28Z Associations of autozygosity with a broad range of human phenotypes 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. Deelen, 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. 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. Afaq, S. Aguilar-Salinas, C.A. Akiyama, M. Albert, M.L. 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. Science & Technology Multidisciplinary Sciences Science & Technology - Other Topics INBREEDING DEPRESSION HOMOZYGOSITY FERTILITY LOCI RUNS QUANTIFICATION 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 Journal Article http://hdl.handle.net/20.500.11937/79988 10.1038/s41467-019-12283-6 English http://creativecommons.org/licenses/by/4.0/ NATURE PUBLISHING GROUP fulltext
spellingShingle	Science & Technology Multidisciplinary Sciences Science & Technology - Other Topics INBREEDING DEPRESSION HOMOZYGOSITY FERTILITY LOCI RUNS QUANTIFICATION 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. Deelen, 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. 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. Afaq, S. Aguilar-Salinas, C.A. Akiyama, M. Albert, M.L. 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. Associations of autozygosity with a broad range of human phenotypes
title	Associations of autozygosity with a broad range of human phenotypes
title_full	Associations of autozygosity with a broad range of human phenotypes
title_fullStr	Associations of autozygosity with a broad range of human phenotypes
title_full_unstemmed	Associations of autozygosity with a broad range of human phenotypes
title_short	Associations of autozygosity with a broad range of human phenotypes
title_sort	associations of autozygosity with a broad range of human phenotypes
topic	Science & Technology Multidisciplinary Sciences Science & Technology - Other Topics INBREEDING DEPRESSION HOMOZYGOSITY FERTILITY LOCI RUNS QUANTIFICATION
url	http://hdl.handle.net/20.500.11937/79988

Associations of autozygosity with a broad range of human phenotypes

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