Can long pregnancy intervals reset the effect of maternal genes?

Abstract

The length of pregnancy is a major determinant of newborn health and varies due to both

environmental and genetic influences, yet their combined effects are not fully understood. The

purpose of this thesis was to examine whether the time interval between pregnancies and a

history of miscarriage alter maternal genetic influences on the timing of delivery. The study

analysed pregnancies from women with more than one previous birth for the interpregnancy

interval models and first pregnancies for the miscarriage models, using full-genome genotype

information and polygenic scores that summarise the inherited contribution to pregnancy

duration. Statistical evaluation was performed with linear regression and genome-wide tests of

gene–environment interaction. The results showed that maternal genetic effects on gestational

duration did not differ substantially across interpregnancy interval categories, although genetic

influences were somewhat stronger at intermediate intervals. A notable interaction was detected

at a genetic region near the gene ATRNL1, where the effect of the maternal allele was stronger

among women with a previous miscarriage, and additional evidence pointed to a miscarriage-

associated pattern of genetic variation at the DPYSL3 locus. These findings indicate that maternal

reproductive history can modify the expression of specific genetic factors that contribute to

pregnancy timing and underline the need for future research integrating molecular data from

relevant reproductive tissues.

Keywords: gestational duration; interpregnancy interval; miscarriage; genome-wide association

study; ATRNL1; DPYSL3