Meta-analysis of genome-wide linkage studies across autoimmune diseases

Abstract

Autoimmune diseases are chronic disorders initiated by a loss of immunologic tolerance to self-antigens. They cluster within families, and patients may be diagnosed with more than one disease, suggesting pleiotropic genes are involved in the aetiology of different diseases. To identify potential loci, which confer susceptibility to autoimmunity independent of disease phenotype, we pooled results from genome-wide linkage studies, using the genome scan meta-analysis method (GSMA). The meta-analysis included 42 independent studies for 11 autoimmune diseases, using 7350 families with 18 291 affected individuals. In addition to the HLA region, which showed highly significant genome-wide evidence for linkage, we obtained suggestive evidence for linkage on chromosome 16, with peak evidence at 10.0-19.8 Mb. This region may harbour a pleiotropic gene (or genes) conferring risk for several diseases, although no such gene has been identified through association studies. We did not identify evidence for linkage at several genes known to confer increased risk to different autoimmune diseases (PTPN22, CTLA4), even in subgroups of diseases consistently found to be associated with these genes. The relative risks conferred by variants in these genes are modest (o1.5 in most cases), and even a large study like this meta-analysis lacks power to detect linkage. This study illustrates the concept that linkage and association studies have power to identify very different types of disease-predisposing variants.

Familial association between type 1 diabetes and other autoimmune and related diseases

“…A familial aggregation of type 1 diabetes with some autoimmune diseases has also been shown. However, to our knowledge this is the first population-level attempt to assess familial risks for type 1 diabetes and a large number of autoimmune and related diseases using unified data [10,11,14,21,24,25,27,28]. The use of hospitalised cases offers advantages and disadvantages for aetiological studies.…”

“…Genetic and epidemiological data indicate that certain autoimmune diseases aggregate in type 1 diabetes families [10,11,[14][15][16][17][18][19][20][21][22][23][24][25]. Reported associated autoimmune and related diseases include coeliac disease, multiple sclerosis, rheumatoid arthritis and autoimmune polyendocrine syndrome [14,21,[26][27][28].…”

Risk of asthma and autoimmune diseases and related conditions in patients hospitalized for obesity

“…Adipokines, leptin and adiponectin, are synthesized in the white adipose tissue at the site of energy storage and they act as links between nutritional status, metabolism and immunity (11,12). Leptin is considered a safety factor regulating body weight by suppressing appetite and stimulating energy expenditure.…”

Nutrigenetics and personalised nutrition: how far have we progressed and are we likely to get there?

“…In these studies genetic variation in O80 % of the human genome is assessed using typically between 100 000 and 1 000 000 marker SNP and information on linkage disequilibrium from the HapMap project (14) . To date, using GWA approaches, O100 susceptibility gene loci for a range of chronic diseases have been confirmed, identified and replicated (15)(16)(17)(18)(19)(20)(21) …”