BACKGROUND: While family history provides important information on risk of developing @entity29 ( @entity29 ), genetic profiling of first degree relatives (FDR) of @entity30 ( @entity30 ) - affected individuals might provide additional information. We aimed to delineate the genetic contribution to the increased @entity29 susceptibility observed in FDR. METHODS: N=976 Caucasian, healthy, non-related FDR; n=4997 independent @entity30 and n=5000 @entity23 ( @entity23 ); were studied. Genotyping for 158 @entity29 -associated single nucleotide polymorphisms (SNPs) was performed using the Illumina Immunochip. Risk allele frequency (RAF) differences between FDR and @entity23 cohorts were correlated with those between @entity30 and @entity23 cohorts. @entity30 and @entity29 genetic risk scores (GRS) were calculated and compared between @entity23 , FDR and @entity30 cohorts. RESULTS: @entity29 -associated SNP RAF differences in FDR and @entity23 cohorts were strongly correlated with those in @entity30 and @entity23 cohorts, correlation coefficient 0.63 [95%CI 0.53 - 0.72], p = 9.90 x 10(-19). There was a significant @entity74 (mean) comparing @entity23 , FDR and @entity30 cohorts: 0.0244, 0.0250 and 0.0257 respectively (p < 1 x 10(-7) for each comparison). There was no significant difference in the @entity29 -GRS between @entity23 and FDR cohorts (p=0.81); however @entity29 -GRS was significantly higher in @entity30 compared with FDR and @entity23 cohorts (p < 10(-10) for each comparison). CONCLUSION: FDR of @entity30 -affected individuals are enriched with @entity29 risk alleles compared with @entity23 . Cumulative @entity30 -specific genetic risk is increased in FDR compared with @entity23 . Prospective studies are required to determine if genotyping would facilitate better risk stratification of FDR.

XXXX Genetic Risk Profile in Healthy First Degree Relatives of @entity30 Patients.

@entity23 :: ('MESH:D007174', 'Disease') :: ['healthy controls', 'HC'] @entity30 :: ('MESH:D003424', 'Disease') :: ['CD', "Crohn's Disease"] @entity74 :: ('MESH:D030342', 'Disease') :: ['increase in CD-GRS'] @entity29 :: ('MESH:D015212', 'Disease') :: ['Inflammatory Bowel Disease', 'IBD']
@entity29 :: (MESH:D015212,Disease) :: ['IBD']
