Parent-of-Origin Effects of the APOB Gene on Adiposity in Young Adults.

Autor: Hagit Hochner, Catherine Allard, Einat Granot-Hershkovitz, Jinbo Chen, Colleen M Sitlani, Sandra Sazdovska, Thomas Lumley, Barbara McKnight, Kenneth Rice, Daniel A Enquobahrie, James B Meigs, Pui Kwok, Marie-France Hivert, Ingrid B Borecki, Felicia Gomez, Ting Wang, Cornelia van Duijn, Najaf Amin, Jerome I Rotter, John Stamatoyannopoulos, Vardiella Meiner, Orly Manor, Josée Dupuis, Yechiel Friedlander, David S Siscovick
Jazyk: angličtina
Rok vydání: 2015
Předmět:
Zdroj: PLoS Genetics, Vol 11, Iss 10, p e1005573 (2015)
Druh dokumentu: article
ISSN: 1553-7390
1553-7404
DOI: 10.1371/journal.pgen.1005573
Popis: Loci identified in genome-wide association studies (GWAS) of cardio-metabolic traits account for a small proportion of the traits' heritability. To date, most association studies have not considered parent-of-origin effects (POEs). Here we report investigation of POEs on adiposity and glycemic traits in young adults. The Jerusalem Perinatal Family Follow-Up Study (JPS), comprising 1250 young adults and their mothers was used for discovery. Focusing on 18 genes identified by previous GWAS as associated with cardio-metabolic traits, we used linear regression to examine the associations of maternally- and paternally-derived offspring minor alleles with body mass index (BMI), waist circumference (WC), fasting glucose and insulin. We replicated and meta-analyzed JPS findings in individuals of European ancestry aged ≤50 belonging to pedigrees from the Framingham Heart Study, Family Heart Study and Erasmus Rucphen Family study (total N≅4800). We considered p0.6). Suggestive maternally-derived associations of rs1367117 were observed with fasting glucose (β = 0.9; 95%CI:0.3,1.5; p = 4.0x10-3) and insulin (ln-transformed, β = 0.06; 95%CI:0.03,0.1; p = 7.4x10-4). Bioinformatic annotation for rs1367117 revealed a variety of regulatory functions in this region in liver and adipose tissues and a 50% methylation pattern in liver only, consistent with allelic-specific methylation, which may indicate tissue-specific POE. Our findings demonstrate a maternal-specific association between a common APOB variant and adiposity, an association that was not previously detected in GWAS. These results provide evidence for the role of regulatory mechanisms, POEs specifically, in adiposity. In addition this study highlights the benefit of utilizing family studies for deciphering the genetic architecture of complex traits.
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