title: Two novel candidate genes identified in adults from the Newfoundland population with addictive tendencies towards food.
abstract: Food addiction (FA) is a distinguished clinical feature affecting about 5% adults of the general population in Canada. FA contributes to obesity, however, the underlying genes in FA are largely unknown. The aim of the current study was to search for FA candidate genes using an exome sequencing followed by a verification study using the most significantly associated identified genes. From a total of 752 adults, 24 subjects were selected including 8 obese with high and 8 obese with low/zero FA clinical symptom score (FAO, NFO), and 8 healthy controls with normal BMI and low/zero FA symptom score (Ctrl). Exome sequencing was completed in all three groups. The top 100 SNPs identified were categorized into 5 subgroups based on gene functions: addiction (Ad), psychological disorders, energy metabolism and obesity, and cancer, unknown function or with other diseases. In the verification study, the top 19 SNPs in the Addiction subgroup were genotyped in the entire 752 subjects using Sequenom iPLEX Gold genotyping technology. Comparison of NFO with Ctrl, and FAO with NFO, Ctrl and the combined group of NFO + Ctrl revealed 19 SNPs associated with Ad genes including, TIRAP, MMADHC, ERAP1, NTM, MYPN, GRID1, ITPR2, GPSM1, ZCCHC14, TNN, PPARD, CACNA1C, SIM1, and DRD2. Genetic association analysis was performed. The major allele A of rs2511521 located in DRD2 (OR = 3.1(95% CI 1.1-8.2)) and the minor allele T of rs625413 located in TIRAP (OR = 2.5(95% CI 1.1-5.8)) in NFO subjects significantly associated with increased risk of food addiction. Using a combination of exome sequencing method and a candidate gene association approach two new FA candidate genes are identified. Further study on the rest of the genes in the other four categories will be warranted.
authors.affiliation: Memorial University, Faculty of Medicine, 300 Prince Philip Drive; St.John's, NL, A1B3V6, Canada. Electronic address: p.pedram@mun.ca.
authors.forename: Pardis
authors.initials: P
authors.lastname: Pedram
authors.affiliation: Memorial University, Faculty of Medicine, 300 Prince Philip Drive; St.John's, NL, A1B3V6, Canada. Electronic address: guangju.zhai@med.mun.ca.
authors.forename: Guangju
authors.initials: G
authors.lastname: Zhai
authors.affiliation: Memorial University, Faculty of Medicine, 300 Prince Philip Drive; St.John's, NL, A1B3V6, Canada. Electronic address: drgulliver@newlabresearch.com.
authors.forename: Wayne
authors.initials: W
authors.lastname: Gulliver
authors.affiliation: Memorial University, Faculty of Medicine, 300 Prince Philip Drive; St.John's, NL, A1B3V6, Canada. Electronic address: hzhang@mun.ca.
authors.forename: Hongwei
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Memorial University, Faculty of Medicine, 300 Prince Philip Drive; St.John's, NL, A1B3V6, Canada. Electronic address: gsun@mun.ca.
authors.forename: Guang
authors.initials: G
authors.lastname: Sun
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D005260:Female; D000073932:Food Addiction / Q000235:genetics*; D056726:Genetic Association Studies; D005838:Genotype; D006801:Humans; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics*; D008875:Middle Aged; D009523:Newfoundland and Labrador; D020641:Polymorphism, Single Nucleotide; D017448:Receptors, Dopamine D2 / Q000235:genetics*; D017472:Receptors, Interleukin-1 / Q000235:genetics*; D000073336:Whole Genome Sequencing; D055815:Young Adult
chemical_list: C581293:DRD2 protein, human; D008562:Membrane Glycoproteins; D017448:Receptors, Dopamine D2; D017472:Receptors, Interleukin-1; C434984:TIRAP protein, human
keywords: Candidate gene association analysis; Exome sequencing; Food addiction; Genetics