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Genetic Mapping of Type 2 Diabetes Patients IDs More Than 100 New Loci

NEW YORK (GenomeWeb) – Researchers led by a team at the University College London reported today in the American Journal of Human Genetics that they conducted genetic mapping of type 2 diabetes patients to identify 111 new loci that may indicate susceptibility to the disease.

Type 2 diabetes is the world's most widespread metabolic disorder. It is also known to be nearly twice as prevalent in the African-American population than in the European-American population (19 percent versus 10 percent). Previously, only 76 loci for the disease were known and studied, and of these very few loci were found in the African-American populations.

"No disease with a genetic predisposition has been more intensely investigated than type 2 diabetes," Nikolas Maniatis, lead author and researcher in the Department of Genetics, Evolution, and Environment at University College of London, said in a statement.

"Before we can conduct the functional studies required in order to better understand the molecular basis of this disease, we first need to identify as many plausible candidate loci as possible," Toby Andrew, co-lead author and researcher at Imperial College of London's Department of Genomics of Common Disease, said. "Genetic maps are key to this task, by integrating the cross-platform genomic data in a biologically meaningful way," he added.

The research team collected 5,800 samples from people with type 2 diabetes and 9,961 control samples from European and African-American populations. The researchers constructed two high-resolution genetic maps — one each for the European and African-American populations

— using HapMap data, based on single nucleotide polymorphisms (SNPs) derived from genome-wide associations. The team conducted in silico functional gene expression analyses to determine whether the same disease loci were also expression quantitative trait loci (eQTL) that regulate the expression of neighboring cis-genes. The researchers also confirmed three of the disease loci using next-gen sequencing and functional annotation.

Based on their results, the researchers added 111 new disease loci for diabetes, bringing the total known loci to 187. The researchers noted that 93 (84 percent) of the newly identified loci are found in both African-American and European populations, and only 18 are European-specific. The team's analysis also revealed that the majority of type 2 diabetes loci confer risk through regulation of expression levels for 266 cis-regulated genes. Most of these genes are not the nearest genes to the associated disease loci.

"Our results mean that we can now target the remaining loci on the genetic maps with deep sequencing to try and find the causal mutations within them," Winston Lau, first author and researcher in UCL's Department of Genetics, Evolution, and Environment, said. "We are also very excited that most of the identified disease loci appear to confer risk of disease in diverse populations such as African Americans, implying our findings are likely to be universally applicable and not just confined to Europeans."

"We are now in a strong position to build upon these genomic results, and we can apply the same methods to other complex diseases such as Alzheimer's disease," concluded Maniatis.