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Four novel coeliac disease regions replicated in an association study of a Swedish-Norwegian family cohort.

Silja Svanström Amundsen ; Julia Rundberg ; Svetlana Adamovic ; Audur Gudjonsdottir ; Henry Ascher ; Johan Ek ; Staffan Nilsson (Institutionen för matematiska vetenskaper, matematisk statistik) ; Benedicte Alexandra Lie ; Åsa Torinsson Naluai ; Ludvig M Sollid
Genes and immunity (1476-5470). Vol. 11 (2010), 1, p. 79-86.
[Artikel, refereegranskad vetenskaplig]

Recent genome-wide association studies have identified 1q31 (RGS1), 2q11-12 (IL18RAP), 3p21 (CCR1/CCR3/CCR2), 3q25-26 (IL12A/SCHIP1), 3q28 (LPP), 4q27 (IL2/IL21), 6q25 (TAGAP) and 12q24 (SH2B3) as susceptibility regions for coeliac disease (CD). We have earlier replicated association with the IL2/IL21 region. This study aimed at replicating the remaining regions in a family cohort using the transmission disequilibrium test, which is not prone to population stratification as a source of false-positive results. Nine single nucleotide polymorphisms (SNPs) within these regions were genotyped in 325 Swedish-Norwegian CD families. We found significant associations with the same alleles in the regions 1q31 (rs2816316; P(nc)=0.0060), 3p21 (rs6441961; P(nc)=0.0006), 3q25-26 (rs17810564; P(nc)=0.0316 and rs9811792; P(nc)=0.0434) and 3q28 (rs1464510; P(nc)=0.0037). Borderline, but non-significant, associations were found for rs917997 (IL18RAP), whereas no evidence for association could be obtained for rs13015714 (IL18RAP) or rs1738074 (TAGAP). The lack of replication of the latter SNPs could be because of limited power. rs3184504 (SH2B3) was not analysed because of assay failure. The most significantly associated region, 3p21 (CCR1/CCR3/CCR2), was further analysed by typing of 30 SNPs, with the aim of identifying the causal variant responsible for the initial association. Several SNPs showed association with CD, but none displayed associations stronger than rs6441961, nor did any of them add to the effect initially marked by rs6441961 in a conditional analysis. However, differential effects of rs6441961(*)C carrying haplotypes were indicated, and we thus cannot exclude the possibility that our inability to obtain evidence for multiple independent effects in the CCR1/CCR3/CCR2 gene region was related to a power issue.

Denna post skapades 2010-01-21. Senast ändrad 2015-01-16.
CPL Pubid: 109724


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Institutioner (Chalmers)

Institutionen för biomedicin, avdelningen för medicinsk genetik och klinisk genetik (GU)
Institutionen för kliniska vetenskaper, sektionen för kvinnors och barns hälsa, Avdelningen för pediatrik (GU)
Institutionen för matematiska vetenskaper, matematisk statistik (2005-2016)



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