Pulmonary arterial hypertension (PAH) is a rare disorder with a poor prognosis. Deleterious variation within components of the transforming growth factor-β pathway, particularly the bone morphogenetic protein type 2 receptor (BMPR2), underlies most heritable forms of PAH. To identify the missing heritability we perform whole-genome sequencing in 1038 PAH index cases and 6385 PAH-negative control subjects. Case-control analyses reveal significant overrepresentation of rare variants in ATP13A3, AQP1 and SOX17, and provide independent validation of a critical role for GDF2 in PAH. We demonstrate familial segregation of mutations in SOX17 and AQP1 with PAH. Mutations in GDF2, encoding a BMPR2 ligand, lead to reduced secretion from transfected cells. In addition, we identify pathogenic mutations in the majority of previously reported PAH genes, and provide evidence for further putative genes. Taken together these findings contribute new insights into the molecular basis of PAH and indicate unexplored pathways for therapeutic intervention.
Pharmacology, Toxicology and Pharmaceutical Science
10
4%
Computer Science
4
2%
Other
17
7%
Unknown
90
36%
Attention Score in Context
Attention Score in Context
This research output has an Altmetric Attention Score of 86. 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 01 November 2023.
All research outputs
#616,719
of 33,979,905 outputs
Outputs from Nature Communications
#10,148
of 81,642 outputs
Outputs of similar age
#10,897
of 371,314 outputs
Outputs of similar age from Nature Communications
#214
of 1,213 outputs
Altmetric has tracked 33,979,905 research outputs across all sources so far. Compared to these this one has done particularly well and is in the 98th percentile: it's in the top 5% of all research outputs ever tracked by Altmetric.
So far Altmetric has tracked 81,642 research outputs from this source. They typically receive a lot more attention than average, with a mean Attention Score of 49.3. This one has done well, scoring higher than 87% of its peers.
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 371,314 tracked outputs that were published within six weeks on either side of this one in any source. This one has done particularly well, scoring higher than 97% of its contemporaries.
We're also able to compare this research output to 1,213 others from the same source and published within six weeks on either side of this one. This one has done well, scoring higher than 82% of its contemporaries.
