Maternal and fetal genetic effects on birth weight and their relevance to cardio-metabolic risk factors

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningfagfællebedømt

Kim F. Michaelsen, Rachel M Freathy, EGG Consortium

Birth weight variation is influenced by fetal and maternal genetic and non-genetic factors, and has been reproducibly associated with future cardio-metabolic health outcomes. In expanded genome-wide association analyses of own birth weight (n = 321,223) and offspring birth weight (n = 230,069 mothers), we identified 190 independent association signals (129 of which are novel). We used structural equation modeling to decompose the contributions of direct fetal and indirect maternal genetic effects, then applied Mendelian randomization to illuminate causal pathways. For example, both indirect maternal and direct fetal genetic effects drive the observational relationship between lower birth weight and higher later blood pressure: maternal blood pressure-raising alleles reduce offspring birth weight, but only direct fetal effects of these alleles, once inherited, increase later offspring blood pressure. Using maternal birth weight-lowering genotypes to proxy for an adverse intrauterine environment provided no evidence that it causally raises offspring blood pressure, indicating that the inverse birth weight–blood pressure association is attributable to genetic effects, and not to intrauterine programming.

OriginalsprogEngelsk
TidsskriftNature Genetics
Vol/bind51
Udgave nummer5
Sider (fra-til)804-814
Antal sider11
ISSN1061-4036
DOI
StatusUdgivet - 2019

Bibliografisk note

CURIS 2019 NEXS 170

ID: 218394621