GENETICS & DISEASE
Medical genetics Markers for bone-fusion disease
A genome-wide association study has identified genetic variations associated with the debilitating disease ankylosing spondylitis
Ankylosing spondylitis (AS) is a chronic inflammatory disease characterized by pain and stiffness in the spine. In extreme cases, AS could lead to abnormal bone formation and fusion of the vertebrae. Genetics is known to play an important role in the develop- ment of AS. Jianjun Liu at the A*STAR Genome Institute of Singapore and co-workers have now conducted a genome-wide association study on the Chinese population and identified two genetic variations that could increase the risk of AS1
. Previous genome-wide association studies on European popu-
lations have already shown that variations in major histocompat- ability complex (MHC) genes — genes that have an important role in immune function — are common in patients with AS. The finding suggests that autoimmune mechanisms play a role in AS, but account for only 20–30% of the risk of inheriting the condition.
Liu and his team performed a two-stage genome-wide asso-
ciation study to identify additional genetic variations. They first analyzed the entire genomes of 1,965 individuals with AS and compared them to those of 4,301 healthy people. All of the study participants were of Chinese Han descent. The researchers used quality control measures to filter the data, and then further analyzed more than 272,000 genetic variants within the genomes from 1,837 of the individuals with AS and 4,231 of the controls. Their analyses not only confirmed that the genetic variations previously identified in European populations are also present in the Chinese Han population, but also identi- fied numerous other variations with the MHC regions of chro- mosome 6, all of which are strongly associated with susceptibility to the condition. The researchers validated the potential variants by further
analysis of the data, and identified two more variations associated with susceptibility, in other regions of the genome. Both of these newly identified variants are located near genes that are known to be involved in cartilage development and bone formation, and may therefore affect how these genes are regulated. The findings support earlier evidence that inflammation and new bone formation occur independently during AS development,
44
and suggest that the processes of cartilage development and bone formation as potential targets for future therapies. “Some variants might be specific to each population,” says Liu.
“However, further direct comparative studies of the samples from different ethnic populations will be needed to identify them.” Liu adds that there are approximately 20–30% of AS patients who have a family history of the disease. His next step is to find out whether the susceptibility variants he identified can help to explain the familial risk further. “We suspect that there are differ- ent variants for the familial risk,” says Liu.
■
1. Lin, Z. et al. A genome-wide association study in Han Chinese identifies new susceptibility loci for ankylosing spondylitis. Nature Genetics 44, 73–77 (2011).
A*STAR RESEARCH OCTOBER 2011– MARCH 2012
©
iStockphoto.com/MedicalArtInc
Page 1 |
Page 2 |
Page 3 |
Page 4 |
Page 5 |
Page 6 |
Page 7 |
Page 8 |
Page 9 |
Page 10 |
Page 11 |
Page 12 |
Page 13 |
Page 14 |
Page 15 |
Page 16 |
Page 17 |
Page 18 |
Page 19 |
Page 20 |
Page 21 |
Page 22 |
Page 23 |
Page 24 |
Page 25 |
Page 26 |
Page 27 |
Page 28 |
Page 29 |
Page 30 |
Page 31 |
Page 32 |
Page 33 |
Page 34 |
Page 35 |
Page 36 |
Page 37 |
Page 38 |
Page 39 |
Page 40 |
Page 41 |
Page 42 |
Page 43 |
Page 44 |
Page 45 |
Page 46 |
Page 47 |
Page 48 |
Page 49 |
Page 50 |
Page 51 |
Page 52 |
Page 53 |
Page 54 |
Page 55 |
Page 56 |
Page 57 |
Page 58 |
Page 59 |
Page 60 |
Page 61 |
Page 62 |
Page 63 |
Page 64 |
Page 65 |
Page 66 |
Page 67 |
Page 68 |
Page 69 |
Page 70 |
Page 71 |
Page 72 |
Page 73 |
Page 74 |
Page 75 |
Page 76 |
Page 77 |
Page 78 |
Page 79 |
Page 80 |
Page 81 |
Page 82 |
Page 83 |
Page 84 |
Page 85 |
Page 86 |
Page 87 |
Page 88 |
Page 89 |
Page 90 |
Page 91 |
Page 92 |
Page 93 |
Page 94 |
Page 95 |
Page 96