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

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


Title: Variant in the synaptonemal complex protein SYCE2 associates with pregnancy loss through effect on recombination
Author: Steinþórsdóttir, Valgerður
Halldórsson, Bjarni Vilhjálmur
Jónsson, Hákon   orcid.org/0000-0001-6197-494X
Palsson, Gunnar
Oddsson, Ásmundur
Westergaard, David
Arnadottir, Gudny A.
Stefánsdóttir, Lilja
Banasik, Karina
Esplin, M. Sean
... 18 more authors Show all authors
Date: 2024-01-29
Language: English
Scope: 4463349
University/Institute: Reykjavik University
Landspitali - The National University Hospital of Iceland
Department: Faculty of Medicine
Other departments
Series: Nature Structural and Molecular Biology; ()
ISSN: 1545-9993
DOI: 10.1038/s41594-023-01209-y
Subject: Barnalæknisfræði; Fæðinga- og kvensjúkdómafræði; Structural Biology; Molecular Biology
URI: https://hdl.handle.net/20.500.11815/4726

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Citation:

Steinþórsdóttir , V , Halldórsson , B V , Jónsson , H , Palsson , G , Oddsson , Á , Westergaard , D , Arnadottir , G A , Stefánsdóttir , 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 , Á , Steingrímsdóttir , Þ , Tryggvadóttir , L , Jónsdóttir , I , Gudbjartsson , D F , Hoffmann , E R , Sulem , P , Hólm , H , Nielsen , H S & Stefánsson , 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

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.

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

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