title: Genome-wide association study of anthropometric traits in Korcula Island, Croatia.
abstract: OBJECTIVE
  To identify genetic variants underlying six anthropometric traits: body height, body weight, body mass index, brachial circumference, waist circumference, and hip circumference, using a genome-wide association study.
  
  
  METHODS
  The study was carried out in the isolated population of the island of Korcula, Croatia, with 898 adult examinees who participated in the larger DNA-based genetic epidemiological study in 2007. Anthropometric measurements followed standard internationally accepted procedures. Examinees were genotyped using HumanHap 370CNV chip by Illumina, with a genome-wide scan containing 316730 single nucleotide polymorphisms (SNP).
  
  
  RESULTS
  A total of 11 SNPs were associated with the investigated traits at the level of P<10(-5), with one SNP (rs7792939 in gene zinc finger protein 498, ZNF498) associated with body weight, hip circumference, and brachial circumference (P=3.59-5.73 x 10(-6)), and another one (rs157350 in gene delta-sarcoglycan, SGCD) with both brachial and hip circumference (P=3.70-6.08 x 10(-6). Variants in CRIM1, a gene regulating delivery of bone morphogenetic proteins to the cell surface, and ITGA1, involved in the regulation of mesenchymal stem cell proliferation and cartilage production, were also associated with brachial circumference (P=7.82 and 9.68 x 10(-6), respectively) and represent interesting functional candidates. Other associations involved those between genes SEZ6L2 and MAX and waist circumference, XTP6 and brachial circumference, and AMPA1/GRIA1 and height.
  
  
  CONCLUSIONS
  Although the study was underpowered for the reported associations to reach formal threshold of genome-wide significance under the assumption of independent multiple testing, the consistency of association between the 2 variants and a set of anthropometric traits makes CRIM1 and ITGA1 highly interesting for further replication and functional follow-up. Increased linkage disequilibrium between the used markers in an isolated population makes the formal significance threshold overly stringent, and changed allele frequencies in isolate population may contribute to identifying variants that would not be easily identified in large outbred populations.
authors.affiliation: Andrija Stampar School of Public Health, School of Medicine, University of Zagreb, Croatia.
authors.forename: Ozren
authors.initials: O
authors.lastname: Polasek
authors.forename: Ana
authors.initials: A
authors.lastname: Marusić
authors.forename: Kresimir
authors.initials: K
authors.lastname: Rotim
authors.forename: Caroline
authors.initials: C
authors.lastname: Hayward
authors.forename: Veronique
authors.initials: V
authors.lastname: Vitart
authors.forename: Jennifer
authors.initials: J
authors.lastname: Huffman
authors.forename: Susan
authors.initials: S
authors.lastname: Campbell
authors.forename: Stipan
authors.initials: S
authors.lastname: Janković
authors.forename: Mladen
authors.initials: M
authors.lastname: Boban
authors.forename: Zrinka
authors.initials: Z
authors.lastname: Biloglav
authors.forename: Ivana
authors.initials: I
authors.lastname: Kolcić
authors.forename: Vjekoslav
authors.initials: V
authors.lastname: Krzelj
authors.forename: Janos
authors.initials: J
authors.lastname: Terzić
authors.forename: Lana
authors.initials: L
authors.lastname: Matec
authors.forename: Gordan
authors.initials: G
authors.lastname: Tometić
authors.forename: Dijana
authors.initials: D
authors.lastname: Nonković
authors.forename: Jasna
authors.initials: J
authors.lastname: Nincević
authors.forename: Marina
authors.initials: M
authors.lastname: Pehlić
authors.forename: Jurica
authors.initials: J
authors.lastname: Zedelj
authors.forename: Vedran
authors.initials: V
authors.lastname: Velagić
authors.forename: Danica
authors.initials: D
authors.lastname: Juricić
authors.forename: Iva
authors.initials: I
authors.lastname: Kirac
authors.forename: Sanja
authors.initials: S
authors.lastname: Belak Kovacević
authors.forename: Alan F
authors.initials: AF
authors.lastname: Wright
authors.forename: Harry
authors.initials: H
authors.lastname: Campbell
authors.forename: Igor
authors.initials: I
authors.lastname: Rudan
mesh_terms: D001827:Body Height / Q000235:genetics*; D001835:Body Weight / Q000235:genetics*; D017523:Croatia; D055106:Genome-Wide Association Study; D005838:Genotype; D006801:Humans; D020641:Polymorphism, Single Nucleotide; D049629:Waist-Hip Ratio