Evaluating the precision of EBF1 SNP x stress interaction association: sex, race, and age differences in a big harmonized data set of 28,026 participants.

Abstract

In prior work, we identified a novel gene-by-stress association of EBF1's common variation (SNP rs4704963) with obesity (i.e., hip, waist) in Whites, which was further strengthened through multiple replications using our synthetic stress measure. We now extend this prior work in a precision medicine framework to find the risk group using harmonized data from 28,026 participants by evaluating the following: (a) EBF1 SNPxSTRESS interaction in Blacks; (b) 3-way interaction of EBF1 SNPxSTRESS with sex, race, and age; and (c) a race and sex-specific path linking EBF1 and stress to obesity to fasting glucose to the development of cardiometabolic disease risk. Our findings provided additional confirmation that genetic variation in EBF1 may contribute to stress-induced human obesity, including in Blacks (P = 0.022) that mainly resulted from race-specific stress due to "racism/discrimination" (P = 0.036) and "not meeting basic needs" (P = 0.053). The EBF1 gene-by-stress interaction differed significantly (P = 1.01e-03) depending on the sex of participants in Whites. Race and age also showed tentative associations (Ps = 0.103, 0.093, respectively) with this interaction. There was a significant and substantially larger path linking EBF1 and stress to obesity to fasting glucose to type 2 diabetes for the EBF1 minor allele group (coefficient = 0.28, P = 0.009, 95% CI = 0.07-0.49) compared with the same path for the EBF1 major allele homozygotes in White females and also a similar pattern of the path in Black females. Underscoring the race-specific key life-stress indicators (e.g., racism/discrimination) and also the utility of our synthetic stress, we identified the potential risk group of EBF1 and stress-induced human obesity and cardiometabolic disease.

Department

Description

Provenance

Subjects

Citation

Published Version (Please cite this version)

10.1038/s41398-020-01028-5

Publication Info

Singh, Abanish, Michael A Babyak, Mario Sims, Solomon K Musani, Beverly H Brummett, Rong Jiang, William E Kraus, Svati H Shah, et al. (2020). Evaluating the precision of EBF1 SNP x stress interaction association: sex, race, and age differences in a big harmonized data set of 28,026 participants. Translational psychiatry, 10(1). p. 351. 10.1038/s41398-020-01028-5 Retrieved from https://hdl.handle.net/10161/21669.

This is constructed from limited available data and may be imprecise. To cite this article, please review & use the official citation provided by the journal.

Scholars@Duke

Babyak

Michael Alan Babyak

Professor Emeritus in Psychiatry and Behavioral Sciences

Since coming to Duke as an intern in 1994 I have collaborated as a biostatistician and co-investigator at Duke on numerous observational and experimental studies involving behavior, psychosocial factors, health, and disease. The substantive topics have ranged across questions concerning exercise and depression, hypertension, weight loss, the genetics of stress and heart disease, sickle cell disease, to name a few. I am particularly interested in the issue of improving reproducibility and transparency in data analysis.

Brummett

Beverly H. Brummett

Associate Professor Emeritus in Psychiatry and Behavioral Sciences

In the early part of my career, my work generally focused on examining psychosocial determinants or correlates (e.g., emotion, personality, and socioeconomic status) of cardiovascular disease.  However, in the past several years, my work has also expanded to include examining how stressful emotional responses, combined with proposed genetic markers, influence metabolic functioning, cognitive decline, functional capacity and quality of live in the elderly, depressive symptomology, and major depressive disorder.  I also have an interest in statistical methodology. 


Unless otherwise indicated, scholarly articles published by Duke faculty members are made available here with a CC-BY-NC (Creative Commons Attribution Non-Commercial) license, as enabled by the Duke Open Access Policy. If you wish to use the materials in ways not already permitted under CC-BY-NC, please consult the copyright owner. Other materials are made available here through the author’s grant of a non-exclusive license to make their work openly accessible.