Linkage at 5q14.3-15 in multiplex systemic lupus erythematosus pedigrees stratified by autoimmune thyroid disease.
OBJECTIVE
To identify genetic effects potentially shared between systemic lupus erythematosus (SLE) and autoimmune thyroiditis (AITD).


METHODS
Families from the Lupus Multiplex Registry and Repository were studied in which there was at least 1 member who had both SLE and AITD (Graves' disease or Hashimoto thyroiditis). Genome scan genotyping findings in these pedigrees were evaluated for evidence of genetic linkage, by the maximum-likelihood parametric method. Nineteen pedigrees were used in the initial genome scan. Subsequently, an independent sample of 16 pedigrees was used to replicate findings.


RESULTS
Studies of the first set of 19 pedigrees yielded a 2-point parametric logarithm of odds (LOD) of 4.97, which was independently confirmed in the replication sample of 16 pedigrees (LOD 2.89). For all 35 pedigrees together, the 2-point LOD was 7.86, under a dominant model used for screening with 90% penetrance and a disease allele frequency of 10%. The multipoint locus homogeneity LOD in the 35 pedigrees was 6.90 (alpha = 1.0) at 5q14.3-15 between D5S1725 and D5S1453, a 12-cM interval, with the peak at D5S1462 at 96.64 cM (nonparametric linkage P = 0.00002). Fine mapping further confirmed the genetic linkage effect and narrowed the region likely to contain the gene to approximately 5 Mb.


CONCLUSIONS
These results suggest that stratifying SLE pedigrees by the presence of other autoimmune disorders may facilitate the discovery of genes related to SLE and that 5q14.3-15 harbors a susceptibility gene shared by SLE and AITD.
Namjou
Bahram
B
Oklahoma Medical Research Foundation, 825 NE 13th Street, Oklahoma City, OK 73104, USA.
Kelly
Jennifer A
JA
Kilpatrick
Jeff
J
Kaufman
Kenneth M
KM
Nath
Swapan K
SK
Scofield
R Hal
RH
Harley
John B
JB
D002895:Chromosomes, Human, Pair 5; D005260:Female; D008040:Genetic Linkage / Q000235:genetics*; D005819:Genetic Markers; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008180:Lupus Erythematosus, Systemic / Q000235:genetics* / Q000276:immunology / Q000473:pathology; D008297:Male; D018895:Microsatellite Repeats; D016017:Odds Ratio; D010375:Pedigree; D012042:Registries; D013967:Thyroiditis, Autoimmune / Q000235:genetics* / Q000276:immunology / Q000473:pathology
D005819:Genetic Markers