Searching for parent-of-origin effects on cardiometabolic traits in imprinted genomic regions

Einat Granot-Hershkovitz, Peitao Wu, David Karasik, Inga Peter, Gina M. Peloso, Daniel Levy, Ramachandran S. Vasan, L. Adrienne Cupples, Ching Ti Liu, James B. Meigs, David S. Siscovick, Josée Dupuis, Yechiel Friedlander, Hagit Hochner*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

4 Scopus citations


Cardiometabolic traits pose a major global public health burden. Large-scale genome-wide association studies (GWAS) have identified multiple loci accounting for up to 30% of the genetic variance in complex traits such as cardiometabolic traits. However, the contribution of parent-of-origin effects (POEs) to complex traits has been largely ignored in GWAS. Family-based studies enable the assessment of POEs in genetic association analyses. We investigated POEs on a range of complex traits in 3 family-based studies. The discovery phase was carried out in large pedigrees from the Kibbutzim Family Study (n = 901 individuals) and in 872 parent–offspring trios from the Jerusalem Perinatal Study. Focusing on imprinted genomic regions, we examined parent-specific associations with 12 complex traits (i.e., body-size, blood pressure, lipids), mostly cardiometabolic risk traits. Forty five of the 11,967 SNPs initially found to have POE were evaluated for replication (p value < 1 × 10−4) in Framingham Heart Study families (max n = 8000 individuals). Three common variants yielded evidence of POE in the meta-analysis. Two variants, located on chr6 in the HLA region, showed a paternal effect on height (rs1042136: βpaternal = −0.023, p value = 1.5 × 10−8 and rs1431403: βpaternal = −0.011, p value = 5.4 × 10−6). The corresponding maternally-derived effects were statistically nonsignificant. The variant rs9332053, located on chr13 in RCBTB2 gene, demonstrated a maternal effect on hip circumference (βmaternal = −4.24, p value = 9.6 × 10−6; βpaternal = 1.29, p value = 0.23). These findings provide evidence for the utility of incorporating POEs into association studies of cardiometabolic traits, especially anthropometric traits. The study highlights the benefits of using family-based data for deciphering the genetic architecture of complex traits.

Original languageAmerican English
Pages (from-to)646-655
Number of pages10
JournalEuropean Journal of Human Genetics
Issue number5
StatePublished - 1 May 2020

Bibliographical note

Publisher Copyright:
© 2020, The Author(s), under exclusive licence to European Society of Human Genetics.


Dive into the research topics of 'Searching for parent-of-origin effects on cardiometabolic traits in imprinted genomic regions'. Together they form a unique fingerprint.

Cite this