Early-onset autoimmune vitiligo associated with an enhancer variant haplotype that upregulates class II HLA expression.

Vitiligo is an autoimmune disease in which melanocyte destruction causes skin depigmentation, with 49 loci known from previous GWAS. Aiming to define vitiligo subtypes, we discovered that age-of-onset is bimodal; one-third of cases have early onset (mean 10.3 years) and two-thirds later onset (mean 34.

Genome-wide association studies of autoimmune vitiligo identify 23 new risk loci and highlight key pathways and regulatory variants.

Vitiligo is an autoimmune disease in which depigmented skin results from the destruction of melanocytes, with epidemiological association with other autoimmune diseases. In previous linkage and genome-wide association studies (GWAS1 and GWAS2), we identified 27 vitiligo susceptibility loci in patients of European ancestry. We carried out a third GWAS (GWAS3) in European-ancestry subjects, with augmented GWAS1 and GWAS2 controls, genome-wide imputation, and meta-analysis of all three GWAS, followed by an independent replication.

Multiplex SNaPshot-a new simple and efficient CYP2D6 and ADRB1 genotyping method.

Background: Reliable, inexpensive, high-throughput genotyping methods are required for clinical trials. Traditional assays require numerous enzyme digestions or are too expensive for large sample volumes. Our objective was to develop an inexpensive, efficient, and reliable assay for CYP2D6 and ADRB1 accounting for numerous polymorphisms including gene duplications.

NLRP1 haplotypes associated with vitiligo and autoimmunity increase interleukin-1β processing via the NLRP1 inflammasome.

Nuclear localization leucine-rich-repeat protein 1 (NLRP1) is a key regulator of the innate immune system, particularly in the skin where, in response to molecular triggers such as pathogen-associated or damage-associated molecular patterns, the NLRP1 inflammasome promotes caspase-1-dependent processing of bioactive interleukin-1β (IL-1β), resulting in IL-1β secretion and downstream inflammatory responses. NLRP1 is genetically associated with risk of several autoimmune diseases including generalized vitiligo, Addison disease, type 1 diabetes, rheumatoid arthritis, and others. Here we identify a repertoire of variation in NLRP1 by deep DNA resequencing.

Genome-wide association analyses identify 13 new susceptibility loci for generalized vitiligo.

We previously reported a genome-wide association study (GWAS) identifying 14 susceptibility loci for generalized vitiligo. We report here a second GWAS (450 individuals with vitiligo (cases) and 3,182 controls), an independent replication study (1,440 cases and 1,316 controls) and a meta-analysis (3,187 cases and 6,723 controls) identifying 13 additional vitiligo-associated loci. These include OCA2-HERC2 (combined P = 3.

Analysis of genomewide association signals for nonsyndromic cleft lip/palate in a Kenya African Cohort.

Nonsyndromic cleft lip with or without cleft palate is a common birth defect with a wide range of prevalence among different populations, apparently highest in Asians and Amerindians and lowest in Africans. Recent genomewide association studies of European-derived and Asian populations have identified six confirmed loci for this phenotype: 1p22.1, 1q32.

Slc7a11 gene controls production of pheomelanin pigment and proliferation of cultured cells.

In mammals, >100 genes regulate pigmentation by means of a wide variety of developmental, cellular, and enzymatic mechanisms. Nevertheless, genes that directly regulate pheomelanin production have not been described. Here, we demonstrate that the subtle gray (sut) mouse pigmentation mutant arose by means of a mutation in the Slc7a11 gene, encoding the plasma membrane cystine/glutamate exchanger xCT [Kanai, Y.

Genome-wide scan of Graves' disease: evidence for linkage on chromosome 5q31 in Chinese Han pedigrees.

Graves' disease (GD), which is a common organ-specific autoimmune disorder, is multifactorial and develops in genetically susceptible individuals. Despite many studies of candidate genes, only associations with human leukocyte antigen and cytotoxic T lymphocyte antigen 4 have been generally detected, and the number of susceptibility genes remains unknown. To identify chromosomal regions contributing to GD, we conducted a genome-wide scan on 322 individuals from 54 Chinese Han multiplex GD pedigrees.

[A linkage study of cytotoxic T lymphocyte-associated antigen 4 gene and Graves' disease in northern Chinese Han ethnic].

Objective: To determine if the cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) gene, which is located on chromosome 2q31-q33, is the major susceptibility gene for Graves' disease (GD) of northern Chinese Han nationality.

Methods: Five highly polymorphic microsatellite markers spanning the entire region of chromosome 2q31-q33 were employed to screen 54 families with multiple incidences of GD (322 individuals) of northern Chinese Han nationality. Tow-point and multi-point Lod scores were calculated under different levels of penetrance, assuming both dominant and recessive models.

[The human major histocompatibility complex region is not a major susceptibility locus for Graves disease among the Hans in north of China].

Objective: To determine if the human major histocompatibility complex (MHC) region located on chromosome 6 p21 is a major susceptibility locus for Graves' disease (GD) among the Hans in North of China.

Methods: Four highly polymorphic microsatellite markers spanning the entire region of chromosome 6 p21 were employed to screen the DNA from blood samples of 54 Han multiplex families with GD (322 individuals) in Liaoning Province, northeast China. Tow-point and multi-point Lod scores were calculated under different levels of penetrance, assuming both dominant and recessive models.