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Genome-wide Association Study of Biochemical Traits in Korčula Island, Croatia
Tatijana Zemunik
; School of Medicine, University of Split, Split, Croatia
Mladen Boban
; School of Medicine, University of Split, Split, Croatia
Gordan Lauc
; School of Medicine, University of Split, Split, Croatia
Stipan Janković
; School of Medicine, University of Split, Split, Croatia
Krešimir Rotim
; Sisters of Mercy University Hospital, Zagreb, Croatia
Zoran Vatavuk
; Sisters of Mercy University Hospital, Zagreb, Croatia
Goran Benčić
; Sisters of Mercy University Hospital, Zagreb, Croatia
Zoran Ðogaš
; School of Medicine, University of Split, Split, Croatia
Vesna Boraska
; School of Medicine, University of Split, Split, Croatia
Vesela Torlak
; University Hospital Split, Split, Croatia
Jelena Sušac
; Vrapče Psychiatric Hospital, Zagreb, Croatia
Ivana Zobić
; Merkur University Hospital, Zagreb, Croatia
Diana Rudan
; Dubrava University Hosapital. Zagreb, Croatia
Danijela Budimir
; School of Medicine, University of Split, Split, Croatia
Grgo Gunjača
; School of Medicine, University of Split, Split, Croatia
Caroline Hayward
; Human Genetics Unit, Medical Research Council, Edinburg, UK
Veronique Vitart
; Human Genetics Unit, Medical Research Council, Edinburg, UK
Alan F. Wright
; Human Genetics Unit, Medical Research Council, Edinburg, UK
Harry Campbell
; The University of Edinburgh Medical School, Edinburgh, UK
Igor Rudan
; The University of Edinburgh Medical School, Edinburgh, UK
Sažetak
Aim To identify genetic variants underlying biochemical
traits – total cholesterol, low-density lipoprotein (LDL) cholesterol,
high-density lipoprotein (HDL) cholesterol, triglycerides,
uric acid, albumin, and fibrinogen, in a genomewide
association study in an isolated population where
rare variants of larger effect may be more easily identified.
Methods The study included 944 adult inhabitants of the
island of Korčula, as a part of larger DNA-based genetic epidemiological
study in 2007. Biochemical measurements
were performed in a single laboratory with stringent internal
and external quality control procedures. Examinees
were genotyped using Human Hap370CNV chip by Illumina,
with a genome-wide scan containing 346 027 single
nucleotide polymorphisms (SNP).
Results A total of 31 SNPs were associated with 7 investigated
traits at the level of P < 1.00 × 10−5. Nine of SNPs
implicated the role of SLC2A9 in uric acid regulation
(P = 4.10 × 10−6-2.58 × 10−12), as previously found in other
populations. All 22 remaining associations fell into the
P = 1.00 × 10−5-1.00 × 10−6 significance range.. One of them
replicated the association between cholesteryl ester transfer
protein (CETP) and HDL, and 7 associations were more
than 100 kilobases away from the closest known gene.
Nearby SNPs, rs4767631 and rs10444502, in gene kinase
suppressor of ras 2 (KSR2) on chromosome 12 were associated
with LDL cholesterol levels, and rs10444502 in the
same gene with total cholesterol levels. Similarly, rs2839619
in gene PBX/knotted 1 homeobox 1 (PKNOX1) on chromosome
21 was associated with total and LDL cholesterol
levels. The remaining 9 findings implied possible associations
between phosphatidylethanolamine N-methyltransferase
(PEMT) gene and total cholesterol; USP46, RAP1GDS1,
and ZCCHC16 genes and triglycerides; BCAT1 and SLC14A2
genes and albumin; and NR3C2, GRIK2, and PCSK2 genes
and fibrinogen.
Conclusion Although this study was underpowered for
most of the reported associations to reach formal threshold
of genome-wide significance under the assumption
of independent multiple testing, replications of previous
findings and consistency of association between the identified
variants and more than one studied trait make such
findings interesting for further functional follow-up studies.
Changed allele frequencies in isolate population may
contribute to identifying variants that would not be easily
identified in much larger samples in outbred populations.
Ključne riječi
total cholesterol; LDL cholesterol; HDL cholesterol; triglycerides; uric acid; albumin; fibrinogen; genome-wide association; isolate; Korčula, Croatia
Hrčak ID:
38304
URI
Datum izdavanja:
15.2.2009.
Posjeta: 1.515 *