| Title |
Exome-chip association analysis reveals an Asian-specific missense variant in PAX4 associated with type 2 diabetes in Chinese individuals
|
|---|---|
| Published in |
Diabetologia, October 2016
|
| DOI | 10.1007/s00125-016-4132-z |
| Pubmed ID | |
| Authors |
Chloe Y. Y. Cheung, Clara S. Tang, Aimin Xu, Chi-Ho Lee, Ka-Wing Au, Lin Xu, Carol H. Y. Fong, Kelvin H. M. Kwok, Wing-Sun Chow, Yu-Cho Woo, Michele M. A. Yuen, JoJo S. H. Hai, Ya-Li Jin, Bernard M. Y. Cheung, Kathryn C. B. Tan, Stacey S. Cherny, Feng Zhu, Tong Zhu, G. Neil Thomas, Kar-Keung Cheng, Chao-Qiang Jiang, Tai-Hing Lam, Hung-Fat Tse, Pak-Chung Sham, Karen S. L. Lam |
| Abstract |
Genome-wide association studies (GWASs) have identified many common type 2 diabetes-associated variants, mostly at the intronic or intergenic regions. Recent advancements of exome-array genotyping platforms have opened up a novel means for detecting the associations of low-frequency or rare coding variants with type 2 diabetes. We conducted an exomechip association analysis to identify additional type 2 diabetes susceptibility variants in the Chinese population. An exome-chip association study was conducted by genotyping 5640 Chinese individuals from Hong Kong, using a custom designed exome array, the Asian Exomechip. Single variant association analysis was conducted on 77,468 single nucleotide polymorphisms (SNPs). Fifteen SNPs were subsequently genotyped for replication analysis in an independent Chinese cohort comprising 12,362 individuals from Guangzhou. A combined analysis involving 7189 cases and 10,813 controls was performed. In the discovery stage, an Asian-specific coding variant rs2233580 (p.Arg192His) in PAX4, and two variants at the known loci, CDKN2B-AS1 and KCNQ1, were significantly associated with type 2 diabetes with exome-wide significance (p discovery < 6.45 × 10(-7)). The risk allele (T) of PAX4 rs2233580 was associated with a younger age at diabetes diagnosis. This variant was replicated in an independent cohort and demonstrated a stronger association that reached genome-wide significance (p meta-analysis [p meta] = 3.74 × 10(-15)) in the combined analysis. We identified the association of a PAX4 Asian-specific missense variant rs2233580 with type 2 diabetes in an exome-chip association analysis, supporting the involvement of PAX4 in the pathogenesis of type 2 diabetes. Our findings suggest PAX4 is a possible effector gene of the 7q32 locus, previously identified from GWAS in Asians. |
X Demographics
The data shown below were collected from the profiles of 8 X users who shared this research output. Click here to find out more about how the information was compiled.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| United States | 3 | 38% |
| Switzerland | 2 | 25% |
| Unknown | 3 | 38% |
Demographic breakdown
| Type | Count | As % |
|---|---|---|
| Members of the public | 5 | 63% |
| Scientists | 3 | 38% |
Mendeley readers
The data shown below were compiled from readership statistics for 23 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Korea, Republic of | 1 | 4% |
| Unknown | 22 | 96% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Student > Bachelor | 4 | 17% |
| Student > Master | 2 | 9% |
| Professor > Associate Professor | 2 | 9% |
| Researcher | 2 | 9% |
| Student > Ph. D. Student | 2 | 9% |
| Other | 4 | 17% |
| Unknown | 7 | 30% |
| Readers by discipline | Count | As % |
|---|---|---|
| Biochemistry, Genetics and Molecular Biology | 6 | 26% |
| Medicine and Dentistry | 5 | 22% |
| Agricultural and Biological Sciences | 4 | 17% |
| Neuroscience | 1 | 4% |
| Unknown | 7 | 30% |
Attention Score in Context
This research output has an Altmetric Attention Score of 4. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 03 January 2017.
All research outputs
#7,486,774
of 25,732,188 outputs
Outputs from Diabetologia
#2,897
of 5,376 outputs
Outputs of similar age
#104,677
of 326,662 outputs
Outputs of similar age from Diabetologia
#60
of 75 outputs
Altmetric has tracked 25,732,188 research outputs across all sources so far. This one has received more attention than most of these and is in the 69th percentile.
So far Altmetric has tracked 5,376 research outputs from this source. They typically receive a lot more attention than average, with a mean Attention Score of 24.7. This one is in the 45th percentile – i.e., 45% of its peers scored the same or lower than it.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 326,662 tracked outputs that were published within six weeks on either side of this one in any source. This one has gotten more attention than average, scoring higher than 66% of its contemporaries.
We're also able to compare this research output to 75 others from the same source and published within six weeks on either side of this one. This one is in the 20th percentile – i.e., 20% of its contemporaries scored the same or lower than it.