title: Multi-variant study of obesity risk genes in African Americans: The Jackson Heart Study.
abstract: OBJECTIVE
  Genome-wide association study (GWAS) has been successful in identifying obesity risk genes by single-variant association analysis. For this study, we designed steps of analysis strategy and aimed to identify multi-variant effects on obesity risk among candidate genes.
  
  
  METHODS
  Our analyses were focused on 2137 African American participants with body mass index measured in the Jackson Heart Study and 657 common single nucleotide polymorphisms (SNPs) genotyped at 8 GWAS-identified obesity risk genes.
  
  
  RESULTS
  Single-variant association test showed that no SNPs reached significance after multiple testing adjustment. The following gene-gene interaction analysis, which was focused on SNPs with unadjusted p-value<0.10, identified 6 significant multi-variant associations. Logistic regression showed that SNPs in these associations did not have significant linear interactions; examination of genetic risk score evidenced that 4 multi-variant associations had significant additive effects of risk SNPs; and haplotype association test presented that all multi-variant associations contained one or several combinations of particular alleles or haplotypes, associated with increased obesity risk.
  
  
  CONCLUSIONS
  Our study evidenced that obesity risk genes generated multi-variant effects, which can be additive or non-linear interactions, and multi-variant study is an important supplement to existing GWAS for understanding genetic effects of obesity risk genes.
authors: Shanghai Children's Medical Center, School of Public Health, Shanghai Jiaotong University School of Medicine, Shanghai 200127, China. Electronic address: arrow64@163.com.
authors: Shijian
authors: S
authors: Liu
authors: Physiology & Biophysics, University of Mississippi Medical Center, Jackson, MS 39216, USA. Electronic address: jgwilson2@umc.edu.
authors: James G
authors: JG
authors: Wilson
authors: Shanghai Children's Medical Center, School of Public Health, Shanghai Jiaotong University School of Medicine, Shanghai 200127, China. Electronic address: fanjiang@shsmu.edu.cn.
authors: Fan
authors: F
authors: Jiang
authors: Department of Data Science, University of Mississippi Medical Center, Jackson, MS 39216, USA. Electronic address: mgriswold@umc.edu.
authors: Michael
authors: M
authors: Griswold
authors: Jackson Heart Study, University of Mississippi Medical Center, Jackson, MS 39216, USA. Electronic address: ACorrea@umc.edu.
authors: Adolfo
authors: A
authors: Correa
authors: Shanghai Children's Medical Center, School of Public Health, Shanghai Jiaotong University School of Medicine, Shanghai 200127, China; Department of Data Science, University of Mississippi Medical Center, Jackson, MS 39216, USA. Electronic address: hmei@umc.edu.
authors: Hao
authors: H
authors: Mei
mesh_terms: D000262:Adenylyl Cyclases / Q000235:genetics; D044383:Black People / Q000235:genetics*; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics; D016022:Case-Control Studies; D015816:Cell Adhesion Molecules, Neuronal / Q000235:genetics; D005260:Female; D058851:GPI-Linked Proteins / Q000235:genetics; D006239:Haplotypes; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000235:genetics; D009419:Nerve Tissue Proteins / Q000235:genetics; D009765:Obesity / Q000208:ethnology / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D044105:Receptor, Melanocortin, Type 4 / Q000235:genetics; D011964:Receptors, Gastrointestinal Hormone / Q000235:genetics; D011978:Receptors, Nicotinic / Q000235:genetics; D050656:Transcription Factor AP-2 / Q000235:genetics; D001741:Black or African American
chemical_list: D000262:Adenylyl Cyclases; D019208:Brain-Derived Neurotrophic Factor; D015816:Cell Adhesion Molecules, Neuronal; D058851:GPI-Linked Proteins; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D044105:Receptor, Melanocortin, Type 4; D011964:Receptors, Gastrointestinal Hormone; D011978:Receptors, Nicotinic; D050656:Transcription Factor AP-2; C470072:MC4R protein, human; C485559:NEGR1 protein, human; C493677:TFAP2B protein, human; C530715:TMEM18 protein, human; C082354:neurexin IIIalpha; C579455:BDNF protein, human; C041086:gastric inhibitory polypeptide receptor; C421784:adenylate cyclase 3
keywords: Gene-gene interaction; Genetic risk score; Haplotype; Obesity; SNP association