Variant in the synaptonemal complex protein SYCE2 associates with pregnancy loss through effect on recombination

Research output: Contribution to journal › Journal article › Research › peer-review

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Variant in the synaptonemal complex protein SYCE2 associates with pregnancy loss through effect on recombination. / Steinthorsdottir, Valgerdur; Halldorsson, Bjarni V.; Jonsson, Hakon; Palsson, Gunnar; Oddsson, Asmundur; Westergaard, David; Arnadottir, Gudny A.; Stefansdottir, Lilja; Banasik, Karina; Esplin, M. Sean; Hansen, Thomas Folkmann; Brunak, Søren; Nyegaard, Mette; Ostrowski, Sisse Rye; Pedersen, Ole Birger Vesterager; Erikstrup, Christian; Thorleifsson, Gudmar; Nadauld, Lincoln D.; Haraldsson, Asgeir; Steingrimsdottir, Thora; Tryggvadottir, Laufey; Jonsdottir, Ingileif; Gudbjartsson, Daniel F.; Hoffmann, Eva R.; Sulem, Patrick; Holm, Hilma; Nielsen, Henriette Svarre; Stefansson, Kari.

In: Nature Structural and Molecular Biology, 2024.

Research output: Contribution to journal › Journal article › Research › peer-review

Harvard

Steinthorsdottir, V, Halldorsson, BV, Jonsson, H, Palsson, G, Oddsson, A, Westergaard, D, Arnadottir, GA, Stefansdottir, L, Banasik, K, Esplin, MS, Hansen, TF, Brunak, S, Nyegaard, M, Ostrowski, SR, Pedersen, OBV, Erikstrup, C, Thorleifsson, G, Nadauld, LD, Haraldsson, A, Steingrimsdottir, T, Tryggvadottir, L, Jonsdottir, I, Gudbjartsson, DF, Hoffmann, ER, Sulem, P, Holm, H, Nielsen, HS & Stefansson, K 2024, 'Variant in the synaptonemal complex protein SYCE2 associates with pregnancy loss through effect on recombination', Nature Structural and Molecular Biology. https://doi.org/10.1038/s41594-023-01209-y

APA

Steinthorsdottir, V., Halldorsson, B. V., Jonsson, H., Palsson, G., Oddsson, A., Westergaard, D., Arnadottir, G. A., Stefansdottir, L., Banasik, K., Esplin, M. S., Hansen, T. F., Brunak, S., Nyegaard, M., Ostrowski, S. R., Pedersen, O. B. V., Erikstrup, C., Thorleifsson, G., Nadauld, L. D., Haraldsson, A., ... Stefansson, K. (2024). Variant in the synaptonemal complex protein SYCE2 associates with pregnancy loss through effect on recombination. Nature Structural and Molecular Biology. https://doi.org/10.1038/s41594-023-01209-y

Vancouver

Steinthorsdottir V, Halldorsson BV, Jonsson H, Palsson G, Oddsson A, Westergaard D et al. Variant in the synaptonemal complex protein SYCE2 associates with pregnancy loss through effect on recombination. Nature Structural and Molecular Biology. 2024. https://doi.org/10.1038/s41594-023-01209-y

Author

Steinthorsdottir, Valgerdur ; Halldorsson, Bjarni V. ; Jonsson, Hakon ; Palsson, Gunnar ; Oddsson, Asmundur ; Westergaard, David ; Arnadottir, Gudny A. ; Stefansdottir, Lilja ; Banasik, Karina ; Esplin, M. Sean ; Hansen, Thomas Folkmann ; Brunak, Søren ; Nyegaard, Mette ; Ostrowski, Sisse Rye ; Pedersen, Ole Birger Vesterager ; Erikstrup, Christian ; Thorleifsson, Gudmar ; Nadauld, Lincoln D. ; Haraldsson, Asgeir ; Steingrimsdottir, Thora ; Tryggvadottir, Laufey ; Jonsdottir, Ingileif ; Gudbjartsson, Daniel F. ; Hoffmann, Eva R. ; Sulem, Patrick ; Holm, Hilma ; Nielsen, Henriette Svarre ; Stefansson, Kari. / Variant in the synaptonemal complex protein SYCE2 associates with pregnancy loss through effect on recombination. In: Nature Structural and Molecular Biology. 2024.

Bibtex

@article{f61113081f404232b2fd1be13c65b989,
title = "Variant in the synaptonemal complex protein SYCE2 associates with pregnancy loss through effect on recombination",
abstract = "Two-thirds of all human conceptions are lost, in most cases before clinical detection. The lack of detailed understanding of the causes of pregnancy losses constrains focused counseling for future pregnancies. We have previously shown that a missense variant in synaptonemal complex central element protein 2 (SYCE2), in a key residue for the assembly of the synaptonemal complex backbone, associates with recombination traits. Here we show that it also increases risk of pregnancy loss in a genome-wide association analysis on 114,761 women with reported pregnancy loss. We further show that the variant associates with more random placement of crossovers and lower recombination rate in longer chromosomes but higher in the shorter ones. These results support the hypothesis that some pregnancy losses are due to failures in recombination. They further demonstrate that variants with a substantial effect on the quality of recombination can be maintained in the population.",
author = "Valgerdur Steinthorsdottir and Halldorsson, {Bjarni V.} and Hakon Jonsson and Gunnar Palsson and Asmundur Oddsson and David Westergaard and Arnadottir, {Gudny A.} and Lilja Stefansdottir and Karina Banasik and Esplin, {M. Sean} and Hansen, {Thomas Folkmann} and S{\o}ren Brunak and Mette Nyegaard and Ostrowski, {Sisse Rye} and Pedersen, {Ole Birger Vesterager} and Christian Erikstrup and Gudmar Thorleifsson and Nadauld, {Lincoln D.} and Asgeir Haraldsson and Thora Steingrimsdottir and Laufey Tryggvadottir and Ingileif Jonsdottir and Gudbjartsson, {Daniel F.} and Hoffmann, {Eva R.} and Patrick Sulem and Hilma Holm and Nielsen, {Henriette Svarre} and Kari Stefansson",
note = "Publisher Copyright: {\textcopyright} 2024, The Author(s).",
year = "2024",
doi = "10.1038/s41594-023-01209-y",
language = "English",
journal = "Nature Structural and Molecular Biology",
issn = "1545-9993",
publisher = "nature publishing group",

}

RIS

TY - JOUR

T1 - Variant in the synaptonemal complex protein SYCE2 associates with pregnancy loss through effect on recombination

AU - Steinthorsdottir, Valgerdur

AU - Halldorsson, Bjarni V.

AU - Jonsson, Hakon

AU - Palsson, Gunnar

AU - Oddsson, Asmundur

AU - Westergaard, David

AU - Arnadottir, Gudny A.

AU - Stefansdottir, Lilja

AU - Banasik, Karina

AU - Esplin, M. Sean

AU - Hansen, Thomas Folkmann

AU - Brunak, Søren

AU - Nyegaard, Mette

AU - Ostrowski, Sisse Rye

AU - Pedersen, Ole Birger Vesterager

AU - Erikstrup, Christian

AU - Thorleifsson, Gudmar

AU - Nadauld, Lincoln D.

AU - Haraldsson, Asgeir

AU - Steingrimsdottir, Thora

AU - Tryggvadottir, Laufey

AU - Jonsdottir, Ingileif

AU - Gudbjartsson, Daniel F.

AU - Hoffmann, Eva R.

AU - Sulem, Patrick

AU - Holm, Hilma

AU - Nielsen, Henriette Svarre

AU - Stefansson, Kari

N1 - Publisher Copyright: © 2024, The Author(s).

PY - 2024

Y1 - 2024

N2 - Two-thirds of all human conceptions are lost, in most cases before clinical detection. The lack of detailed understanding of the causes of pregnancy losses constrains focused counseling for future pregnancies. We have previously shown that a missense variant in synaptonemal complex central element protein 2 (SYCE2), in a key residue for the assembly of the synaptonemal complex backbone, associates with recombination traits. Here we show that it also increases risk of pregnancy loss in a genome-wide association analysis on 114,761 women with reported pregnancy loss. We further show that the variant associates with more random placement of crossovers and lower recombination rate in longer chromosomes but higher in the shorter ones. These results support the hypothesis that some pregnancy losses are due to failures in recombination. They further demonstrate that variants with a substantial effect on the quality of recombination can be maintained in the population.

AB - Two-thirds of all human conceptions are lost, in most cases before clinical detection. The lack of detailed understanding of the causes of pregnancy losses constrains focused counseling for future pregnancies. We have previously shown that a missense variant in synaptonemal complex central element protein 2 (SYCE2), in a key residue for the assembly of the synaptonemal complex backbone, associates with recombination traits. Here we show that it also increases risk of pregnancy loss in a genome-wide association analysis on 114,761 women with reported pregnancy loss. We further show that the variant associates with more random placement of crossovers and lower recombination rate in longer chromosomes but higher in the shorter ones. These results support the hypothesis that some pregnancy losses are due to failures in recombination. They further demonstrate that variants with a substantial effect on the quality of recombination can be maintained in the population.

U2 - 10.1038/s41594-023-01209-y

DO - 10.1038/s41594-023-01209-y

M3 - Journal article

C2 - 38287193

AN - SCOPUS:85183620302

JO - Nature Structural and Molecular Biology

JF - Nature Structural and Molecular Biology

SN - 1545-9993

ER -

ID: 381786253