TY - JOUR
T1 - Suggestive evidence for association of human chromosome 18q12-q21 and its orthologue on rat and mouse chromosome 18 with several autoimmune diseases
AU - Merriman, Tony R.
AU - Cordell, Heather J.
AU - Eaves, Iain A.
AU - Danoy, Patrick A.
AU - Coraddu, Francesca
AU - Barber, Rachael
AU - Cucca, Francesco
AU - Broadley, Simon
AU - Sawcer, Stephen
AU - Compston, Alastair
AU - Wordsworth, Paul
AU - Shatford, Jane
AU - Laval, Steve
AU - Jirholt, Johan
AU - Holmdahl, Rikard
AU - Theofilopoulos, Argyrios N.
AU - Kono, Dwight H.
AU - Tuomilehto, Jaakko
AU - Tuomilehto-Wolf, Eva
AU - Buzzetti, Raffaella
AU - Marrosu, Maria Giovanna
AU - Undlien, Dag E.
AU - Rønningen, Kjersti S.
AU - Ionesco-Tirgoviste, C.
AU - Shield, Julian P.
AU - Pociot, Fleming
AU - Nerup, Jorn
AU - Jacob, Chaim O.
AU - Polychronakos, Constantin
AU - Bain, Steve C.
AU - Todd, John A.
PY - 2001/1/1
Y1 - 2001/1/1
N2 - Some immune system disorders, such as type 1 diabetes, multiple sclerosis (MS), and rheumatoid arthritis (RA), share common features: the presence of autoantibodies and serf-reactive T-cells, and a genetic association with the major histocompatibility complex. We have previously published evidence, from 1,708 families, for linkage and association of a haplotype of three markers in the D18S487 region of chromosome 18q21 with type 1 diabetes. Here, the three markers were typed in an independent set of 627 families and, although there was evidence for linkage (maximum logarithm of odds score [MLS] = 1.2; P = 0.02), no association was detected. Further linkage analysis revealed suggestive evidence for linkage of chromosome 18q21 to type 1 diabetes in 882 multiplex families (MLS = 2.2; λs = 1.2; P = 0.001), and by meta-analysis the orthologous region (also on chromosome 18) is linked to diabetes in rodents (P = 9 × 10-4). By meta-analysis, both human chromosome 18q12-q21 and the rodent orthologous region show positive evidence for linkage to an autoimmune phenotype (P = 0.004 and 2 × 10-8, respectively, empirical P = 0.01 and 2 × 10-4, respectively). In the diabetes-linked region of chromosome 18q12-q21, a candidate gene, deleted in colorectal carcinoma (DCC), was tested for association with human autoimmunity in 3,380 families with type 1 diabetes, MS, and RA. A haplotype ("2-10") of two newly characterized microsatellite markers within DCC showed evidence for association with autoimmunity (P = 5 × 10-6). Collectively, these data suggest that a locus (or loci) exists on human chromosome 18q12-q21 that influences multiple autoimmune diseases and that this association might be conserved between species.
AB - Some immune system disorders, such as type 1 diabetes, multiple sclerosis (MS), and rheumatoid arthritis (RA), share common features: the presence of autoantibodies and serf-reactive T-cells, and a genetic association with the major histocompatibility complex. We have previously published evidence, from 1,708 families, for linkage and association of a haplotype of three markers in the D18S487 region of chromosome 18q21 with type 1 diabetes. Here, the three markers were typed in an independent set of 627 families and, although there was evidence for linkage (maximum logarithm of odds score [MLS] = 1.2; P = 0.02), no association was detected. Further linkage analysis revealed suggestive evidence for linkage of chromosome 18q21 to type 1 diabetes in 882 multiplex families (MLS = 2.2; λs = 1.2; P = 0.001), and by meta-analysis the orthologous region (also on chromosome 18) is linked to diabetes in rodents (P = 9 × 10-4). By meta-analysis, both human chromosome 18q12-q21 and the rodent orthologous region show positive evidence for linkage to an autoimmune phenotype (P = 0.004 and 2 × 10-8, respectively, empirical P = 0.01 and 2 × 10-4, respectively). In the diabetes-linked region of chromosome 18q12-q21, a candidate gene, deleted in colorectal carcinoma (DCC), was tested for association with human autoimmunity in 3,380 families with type 1 diabetes, MS, and RA. A haplotype ("2-10") of two newly characterized microsatellite markers within DCC showed evidence for association with autoimmunity (P = 5 × 10-6). Collectively, these data suggest that a locus (or loci) exists on human chromosome 18q12-q21 that influences multiple autoimmune diseases and that this association might be conserved between species.
UR - http://www.scopus.com/inward/record.url?scp=0035152589&partnerID=8YFLogxK
U2 - 10.2337/diabetes.50.1.184
DO - 10.2337/diabetes.50.1.184
M3 - Journal article
C2 - 11147786
AN - SCOPUS:0035152589
SN - 0012-1797
VL - 50
SP - 184
EP - 194
JO - Diabetes
JF - Diabetes
IS - 1
ER -