title: Genome-wide analysis identifies an african-specific variant in SEMA4D associated with body mass index.
abstract: The prevalence of obesity varies between ethnic groups. No genome-wide association study (GWAS) for body mass index (BMI) has been conducted in continental Africans.
  
  
  
  We performed a GWAS for BMI in 1,570 West Africans (WA). Replication was conducted in independent samples of WA (n = 1,411) and African Americans (AA) (n = 9,020).
  
  
  
  We identified a novel genome-wide significant African-specific locus for BMI (SEMA4D, rs80068415; minor allele frequency = 0.008, P = 2.10 × 10-8). This finding was replicated in independent samples of WA (P = 0.013) and AA (P = 0.017). Individuals with obesity had higher serum SEMA4D levels compared to those without obesity (P < 0.0001), and elevated levels of serum SEMA4D were associated with increased obesity risk (OR = 4.2, P < 1 × 10-4). The prevalence of obesity was higher in individuals with the CT versus TT genotypes (55.6% vs. 22.9%).
  
  
  
  A novel variant in SEMA4D was significantly associated with BMI. Carriers of the C allele were 4.6 BMI units heavier than carriers of the T allele (P = 0.0007). This variant is monomorphic in Europeans and Asians, highlighting the importance of studying diverse populations. While there is evidence for the involvement of SEMA4D in inflammatory processes, this study is the first to implicate SEMA4D in obesity pathophysiology.
authors.affiliation: Center for Research on Genomics and Global Health, National Human Genome Research Institute, National Institutes of Health, Bethesda, Maryland, USA, 20892.
authors.forename: Guanjie
authors.initials: G
authors.lastname: Chen
authors.affiliation: Center for Research on Genomics and Global Health, National Human Genome Research Institute, National Institutes of Health, Bethesda, Maryland, USA, 20892.
authors.forename: Ayo P
authors.initials: AP
authors.lastname: Doumatey
authors.affiliation: Center for Research on Genomics and Global Health, National Human Genome Research Institute, National Institutes of Health, Bethesda, Maryland, USA, 20892.
authors.forename: Jie
authors.initials: J
authors.lastname: Zhou
authors.affiliation: Center for Research on Genomics and Global Health, National Human Genome Research Institute, National Institutes of Health, Bethesda, Maryland, USA, 20892.
authors.forename: Lin
authors.initials: L
authors.lastname: Lei
authors.affiliation: Center for Research on Genomics and Global Health, National Human Genome Research Institute, National Institutes of Health, Bethesda, Maryland, USA, 20892.
authors.forename: Amy R
authors.initials: AR
authors.lastname: Bentley
authors.affiliation: Center for Research on Genomics and Global Health, National Human Genome Research Institute, National Institutes of Health, Bethesda, Maryland, USA, 20892.
authors.forename: Fasil
authors.initials: F
authors.lastname: Tekola-Ayele
authors.affiliation: Center for Research on Genomics and Global Health, National Human Genome Research Institute, National Institutes of Health, Bethesda, Maryland, USA, 20892.
authors.forename: Sally N
authors.initials: SN
authors.lastname: Adebamowo
authors.affiliation: Center for Research on Genomics and Global Health, National Human Genome Research Institute, National Institutes of Health, Bethesda, Maryland, USA, 20892.
authors.forename: Jennifer L
authors.initials: JL
authors.lastname: Baker
authors.affiliation: University of Lagos, College of Medicine, Endocrine and Metabolic Unit, Lagos, Nigeria.
authors.forename: Olufemi
authors.initials: O
authors.lastname: Fasanmade
authors.affiliation: University of Nigeria Teaching Hospital, Department of Hematology, Enugu, Nigeria.
authors.forename: Godfrey
authors.initials: G
authors.lastname: Okafor
authors.affiliation: University of Science and Technology, Department of Medicine, Kumasi, Ghana.
authors.forename: Benjamin
authors.initials: B
authors.lastname: Eghan
authors.affiliation: University of Science and Technology, Department of Medicine, Kumasi, Ghana.
authors.forename: Kofi
authors.initials: K
authors.lastname: Agyenim-Boateng
authors.affiliation: University of Ghana Medical School, Department of Medicine and Therapeutics, Accra, Ghana.
authors.forename: Albert
authors.initials: A
authors.lastname: Amoah
authors.affiliation: University of Maryland School of Medicine, Baltimore, Maryland, USA.
authors.forename: Clement
authors.initials: C
authors.lastname: Adebamowo
authors.affiliation: University of Science and Technology, Department of Medicine, Kumasi, Ghana.
authors.forename: Joseph
authors.initials: J
authors.lastname: Acheampong
authors.affiliation: University of Lagos, College of Medicine, Endocrine and Metabolic Unit, Lagos, Nigeria.
authors.forename: Thomas
authors.initials: T
authors.lastname: Johnson
authors.affiliation: University of Nigeria Teaching Hospital, Department of Hematology, Enugu, Nigeria.
authors.forename: Johnnie
authors.initials: J
authors.lastname: Oli
authors.affiliation: Center for Research on Genomics and Global Health, National Human Genome Research Institute, National Institutes of Health, Bethesda, Maryland, USA, 20892.
authors.forename: Daniel
authors.initials: D
authors.lastname: Shriner
authors.affiliation: Center for Research on Genomics and Global Health, National Human Genome Research Institute, National Institutes of Health, Bethesda, Maryland, USA, 20892.
authors.forename: Adebowale A
authors.initials: AA
authors.lastname: Adeyemo
authors.affiliation: Center for Research on Genomics and Global Health, National Human Genome Research Institute, National Institutes of Health, Bethesda, Maryland, USA, 20892.
authors.forename: Charles N
authors.initials: CN
authors.lastname: Rotimi
mesh_terms: D000354:Africa, Western; D000483:Alleles; D015703:Antigens, CD / Q000097:blood / Q000235:genetics*; D044383:Black People / Q000235:genetics*; D015992:Body Mass Index; D005260:Female; D005787:Gene Frequency; D055106:Genome-Wide Association Study; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D039961:Semaphorins / Q000097:blood / Q000235:genetics*; D001741:Black or African American
chemical_list: D015703:Antigens, CD; C093224:CD100 antigen; D039961:Semaphorins