Systems genetic analysis of binge‐like eating in a C57BL/6J x DBA/2J‐F2 cross

Abstract

Binge eating is a heritable trait associated with eating disorders and refers to the rapid consumption of a large quantity of energy‐dense food that is, associated with loss of control and negative affect. Binge eating disorder is the most common eating disorder in the United States; however, the genetic basis is unknown. We previously identified robust mouse inbred strain differences between C57BL/6J and DBA/2J in binge‐like eating of sweetened palatable food in an intermittent access, conditioned place preference paradigm. To map the genetic basis of changes in body weight and binge‐like eating (BLE) and to identify candidate genes, we conducted quantitative trait locus (QTL) analysis in 128 C57BL/6J x DBA/2J‐F2 mice combined with PheQTL and trait covariance analysis in GeneNetwork2 using legacy BXD‐RI trait datasets. We identified a QTL on Chromosome 18 influencing changes in body weight across days in females (log of the odds [LOD] = 6.3; 1.5‐LOD: 3–12 cM) that contains the candidate gene Zeb1. We also identified a sex‐combined QTL influencing initial palatable food intake on Chromosome 5 (LOD = 5.8; 1.5‐LOD: 21–28 cM) that contains the candidate gene Lcorl and a second QTL influencing escalated palatable food intake on Chromosome 6 in males (LOD = 5.4; 1.5‐LOD: 50–59 cM) that contains the candidate genes Adipor2 and Plxnd1. Finally, we identified a suggestive QTL in females for slope of BLE on distal Chromosome 18 (LOD = 4.1; p = 0.055; 1.5‐LOD: 23–35 cM). Future studies will use BXD‐RI strains to fine map loci and support candidate gene nomination for gene editing.

Genetics and neurobiology of eating disorders

“…The study of BLE with increased genetic diversity, additional diets (high fat diet), and environmental variables will increase gene identification. In support, a recent study involving a cross between the BLE-prone DBA/2J strain with the BLE-resistant C57BL/6J strain 92 identified multiple QTLs influencing eating behavior and body weight, including a sex-combined QTL containing the candidate gene Lcorl that influences initial consumption of palatable food, a female-selective locus containing the candidate gene Zeb1 underlying changes in body weight during BLE, and a male-selective locus for escalation in palatable food intake that contains the candidate genes Adipor2 and Plxnd1 97 .…”

Atp1a2 and Kcnj9 are candidate genes underlying oxycodone behavioral sensitivity and withdrawal in C57BL/6 substrains

“…Genetic regulation of gene expression (eQTLs) provides a functional link and causal support for quantitative trait genes/variants underlying behavior 23,43,44,51 . Using a striatal RNA-seq dataset from 23 F2 mice that had undergone OXY-CPP testing, two weeks of high-dose OXY treatment (20 mg/kg, i.p.…”

Genotype imputation in F2 crosses of inbred lines

“…the statistical technique to infer missing data), and statistical models have been specifically developed for the linked inheritance patterns of DNA sequence variation. Imputation approaches have been used for plant breeding ( Bhattarai et al 2020 ), farm animal agricultural studies ( Li et al 2022 ), and model organism studies ( Yao et al 2021 ).…”