Izvorni znanstveni članak
Genome-wide Association Study of Anthropometric Traits in Korčula Island, Croatia
Ozren Polašek
; Adrija Štampar School Of Public Health, Zagreb, Croatia
Ana Marušić
; School of Medicine, University of Split, Croatia
Krešimir Rotim
; Sisters of Mercy University Hospital, Zagreb, Croatia
Caroline Hayward
; Human Genetics Unit, Western General Hospital, Edinburg, UK
Veronique Vitart
; Human Genetics Unit, Western General Hospital, Edinburg, UK
Jennifer Huffman
; Human Genetics Unit, Western General Hospital, Edinburg, UK
Susan Campbell
; Human Genetics Unit, Western General Hospital, Edinburg, UK
Stipan Janković
; School of Medicine, University of Split, Croatia
Mladen Boban
; School of Medicine, University of Split, Croatia
Zrinka Biloglav
; Adrija Štampar School Of Public Health, Zagreb, Croatia
Ivana Kolčić
; Adrija Štampar School Of Public Health, Zagreb, Croatia
Vjekoslav Krželj
; School of Medicine, University of Split, Croatia
Janoš Terzić
; School of Medicine, University of Split, Croatia
Lana Matec
; Emergency Medicine Unit, Zagreb, Croatia
Gordan Tometić
; University Hospital for Tumors, Zagreb, Croatia
Dijana Nonković
; Institute for Public Health, Split, Croatia
Jasna Ninčević
; Institute for Public Health, Split, Croatia
Marina Pehlić
; School of Medicine, University of Split, Croatia
Jurica Žedelj
; Mali Lošinj Health Centre, Mali Lošinj, Croatia
Vedran Velagić
; Zagreb University Hospital Center, Zagreb, Croatia
Danica Juričić
; Zagreb University Hospital Center, Zagreb, Croatia
Iva Kirac
; Sisters of Mercy University Hospital, Zagreb, Croatia
Sanja Belak Kovačević
; Fran Mihaljević University Hospital for Infectious Diseases, Zagreb, Croatia
Alan F. Wright
; Human Genetics Unit, Western General Hospital, Edinburg, UK
Harry Campbell
; Department of Public Health Sciences, Zhe University of Edinburg Medical School, Edinburg, UK
Igor Rudan
; Department of Public Health Sciences, Zhe University of Edinburg Medical School, Edinburg, UK
Sažetak
Aim 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 Korčula, 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
316 730 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 × 10−6), and another one (rs157350 in
gene delta-sarcoglycan, SGCD) with both brachial and hip
circumference (P = 3.70-6.08 × 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 × 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.
Conclusion 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.
Ključne riječi
total cholesterol; LDL cholesterol; HDL cholesterol; triglycerides; uric acid; albumin; fibrinogen; genome-wide association; isolate; Korčula; Croatia
Hrčak ID:
38302
URI
Datum izdavanja:
15.2.2009.
Posjeta: 1.413 *