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Whole genome sequencing in 1038 index cases reveals novel causative genes in pulmonary arterial hypertension

Pulmonary arterial hypertension (PAH) is a rare disorder with a poor prognosis. Deleterious variation within genes encoding components of the transforming growth factor-ß pathway underlie the majority of heritable forms of PAH. Identifying the missing genetic contribution is challenging, even with genes of large effect size, since it likely involves mutations in genes confined to small numbers of PAH cases. In this study, we performed whole genome sequencing, comparing 1038 PAH index cases to 6385 subjects with other rare diseases. Rare variant analysis identified mutations in novel causal genes, namely ATP13A3, AQP1 and SOX17, and provided independent validation of a critical role for GDF2 in PAH. We detected mutations predicted to be disruptive of function in most, but not all, previously reported PAH genes. Taken together these findings provide new insights into the molecular basis of PAH, and support a central role for endothelial dysregulation in disease pathogenesis.

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Studies are experimental investigations of a particular phenomenon, e.g., case-control studies on a particular trait or cancer research projects reporting matching cancer normal genomes from patients.

Study ID Study Title Study Type
EGAS00001001012 Other

This table displays only public information pertaining to the files in the dataset. If you wish to access this dataset, please submit a request. If you already have access to these data files, please consult the download documentation.

ID File Type Size Located in
EGAF00000661007 cram 47.7 GB
EGAF00000663025 cram 42.0 GB
EGAF00000663031 cram 42.3 GB
EGAF00000663058 cram 37.3 GB
EGAF00000690144 cram 36.4 GB
EGAF00000690157 cram 31.9 GB
EGAF00000690158 cram 31.7 GB
EGAF00000690163 cram 32.6 GB
EGAF00000690164 cram 33.6 GB
EGAF00000690169 cram 31.5 GB
EGAF00000690185 cram 46.3 GB
EGAF00000690186 cram 42.0 GB
EGAF00000690192 cram 43.5 GB
EGAF00000690230 cram 41.7 GB
EGAF00000690243 cram 37.8 GB
EGAF00000690247 cram 37.9 GB
EGAF00000690252 cram 33.9 GB
EGAF00000690255 cram 39.6 GB
EGAF00000690256 cram 40.0 GB
EGAF00000690261 cram 40.2 GB
EGAF00000690262 cram 39.9 GB
EGAF00000690266 cram 40.5 GB
EGAF00000690271 cram 34.8 GB
EGAF00000690276 cram 35.8 GB
EGAF00000690281 cram 38.3 GB
EGAF00000690282 cram 39.1 GB
EGAF00000690284 cram 38.2 GB
EGAF00000690285 cram 38.7 GB
EGAF00000690287 cram 38.5 GB
EGAF00000690288 cram 39.0 GB
EGAF00000690290 cram 40.3 GB
EGAF00000690292 cram 39.2 GB
EGAF00000690294 cram 40.0 GB
EGAF00000690295 cram 40.2 GB
EGAF00000690301 cram 37.4 GB
EGAF00000691124 cram 41.8 GB
EGAF00000694862 cram 47.8 GB
EGAF00000695473 cram 45.3 GB
EGAF00000697839 cram 44.4 GB
EGAF00000702149 cram 38.3 GB
EGAF00000702470 cram 60.5 GB
EGAF00000702475 cram 53.2 GB
EGAF00000705543 cram 37.1 GB
EGAF00000705549 cram 36.6 GB
EGAF00000705554 cram 37.8 GB
EGAF00000705563 cram 37.8 GB
EGAF00000705565 cram 38.3 GB
EGAF00000705568 cram 36.9 GB
EGAF00000765437 cram 40.7 GB
EGAF00000765439 cram 39.8 GB
EGAF00000765442 cram 40.0 GB
EGAF00000766538 cram 36.5 GB
EGAF00000767993 cram 33.1 GB
EGAF00000768001 cram 35.9 GB
EGAF00000788919 cram 42.1 GB
EGAF00000789281 cram 43.8 GB
EGAF00000789283 cram 38.1 GB
EGAF00000789285 cram 40.7 GB
EGAF00000798105 cram 49.0 GB
EGAF00000798106 cram 49.5 GB
EGAF00000798115 cram 42.2 GB
EGAF00000798124 cram 37.2 GB
EGAF00000798125 cram 40.3 GB
EGAF00000798126 cram 42.7 GB
EGAF00000798144 cram 36.7 GB
EGAF00000798146 cram 39.3 GB
EGAF00000799373 cram 41.2 GB
EGAF00000799375 cram 43.1 GB
EGAF00000799377 cram 42.8 GB
EGAF00000799379 cram 40.6 GB
EGAF00000799386 cram 44.7 GB
EGAF00000799393 cram 40.6 GB
EGAF00000799394 cram 60.8 GB
EGAF00000799395 cram 43.1 GB
EGAF00000799422 cram 39.1 GB
EGAF00000799427 cram 39.1 GB
EGAF00000799430 cram 34.7 GB
EGAF00000799432 cram 36.5 GB
EGAF00000799435 cram 37.9 GB
EGAF00000799437 cram 38.6 GB
EGAF00000799438 cram 38.7 GB
EGAF00000799443 cram 36.8 GB
EGAF00000799444 cram 38.1 GB
EGAF00000799445 cram 38.0 GB
EGAF00000823922 cram 51.5 GB
EGAF00000823933 cram 45.9 GB
EGAF00000823943 cram 52.4 GB
EGAF00000824026 cram 31.0 GB
EGAF00000824309 cram 36.6 GB
EGAF00000825828 cram 34.3 GB
EGAF00000825879 cram 43.3 GB
EGAF00000825888 cram 32.5 GB
EGAF00000825895 cram 31.9 GB
EGAF00000825902 cram 39.2 GB
EGAF00000826219 cram 45.9 GB
EGAF00000834545 cram 40.2 GB
EGAF00000834546 cram 39.2 GB
EGAF00000834548 cram 38.1 GB
EGAF00000835510 cram 75.3 GB
EGAF00000859326 cram 57.6 GB
EGAF00000862757 cram 42.8 GB
EGAF00000862763 cram 42.0 GB
EGAF00000862767 cram 40.0 GB
EGAF00000862768 cram 41.8 GB
EGAF00000862773 cram 41.6 GB
EGAF00000863993 cram 42.9 GB
EGAF00000863996 cram 42.6 GB
EGAF00000864003 cram 40.7 GB
EGAF00000864004 cram 41.1 GB
EGAF00000864006 cram 39.9 GB
EGAF00000864007 cram 40.1 GB
EGAF00000864008 cram 40.6 GB
EGAF00000864009 cram 41.0 GB
EGAF00000864010 cram 38.7 GB
EGAF00000864011 cram 40.8 GB
EGAF00000864012 cram 38.9 GB
EGAF00000864013 cram 41.1 GB
EGAF00000864018 cram 39.7 GB
EGAF00000864026 cram 38.9 GB
EGAF00000864028 cram 37.6 GB
EGAF00000864030 cram 42.0 GB
EGAF00000864031 cram 39.2 GB
EGAF00000864032 cram 41.3 GB
EGAF00000864033 cram 40.1 GB
EGAF00000864036 cram 41.2 GB
EGAF00000864038 cram 38.1 GB
EGAF00000881406 cram 41.6 GB
EGAF00000881439 cram 41.2 GB
EGAF00000881444 cram 38.3 GB
EGAF00000881446 cram 38.5 GB
EGAF00000882790 cram 38.1 GB
EGAF00000882797 cram 37.3 GB
EGAF00000882805 cram 38.1 GB
EGAF00000882845 cram 40.1 GB
EGAF00000883159 cram 42.6 GB
EGAF00000883171 cram 41.3 GB
EGAF00000883323 cram 39.1 GB
EGAF00000883326 cram 40.3 GB
EGAF00000883340 cram 39.8 GB
EGAF00000884261 cram 38.8 GB
EGAF00000884263 cram 38.8 GB
EGAF00000884267 cram 37.4 GB
EGAF00000884373 cram 42.1 GB
EGAF00000884379 cram 40.1 GB
EGAF00000884382 cram 38.4 GB
EGAF00000884747 cram 37.2 GB
EGAF00000884752 cram 37.8 GB
EGAF00000884753 cram 36.7 GB
EGAF00000884755 cram 36.2 GB
EGAF00000884760 cram 36.3 GB
EGAF00000896366 cram 38.2 GB
EGAF00000900009 cram 38.0 GB
EGAF00000900028 cram 39.2 GB
EGAF00000900570 cram 36.9 GB
EGAF00000900583 cram 35.3 GB
EGAF00000900593 cram 37.4 GB
EGAF00000902980 cram 50.9 GB
EGAF00000903777 cram 40.9 GB
EGAF00000905685 cram 39.8 GB
EGAF00000905708 cram 38.1 GB
EGAF00000905958 cram 41.4 GB
EGAF00000905982 cram 37.1 GB
EGAF00000905990 cram 40.2 GB
EGAF00000907818 cram 40.8 GB
EGAF00000907834 cram 38.8 GB
EGAF00000907844 cram 40.1 GB
EGAF00000908336 cram 36.3 GB
EGAF00000908337 cram 37.4 GB
EGAF00000908424 cram 36.9 GB
EGAF00000918249 cram 38.5 GB
EGAF00000918258 cram 40.0 GB
EGAF00000918261 cram 37.0 GB
EGAF00000922478 cram 35.9 GB
EGAF00000933519 cram 38.4 GB
EGAF00000933520 cram 32.5 GB
EGAF00000933523 cram 39.1 GB
EGAF00000933524 cram 38.3 GB
EGAF00000933528 cram 41.5 GB
EGAF00000933529 cram 39.2 GB
EGAF00000933531 cram 40.5 GB
EGAF00000933535 cram 37.0 GB
EGAF00000933537 cram 39.1 GB
EGAF00000933538 cram 35.4 GB
EGAF00000937534 cram 33.1 GB
EGAF00000937545 cram 36.8 GB
EGAF00000937547 cram 38.0 GB
EGAF00000937548 cram 39.7 GB
EGAF00000937553 cram 39.3 GB
EGAF00000937556 cram 35.8 GB
EGAF00000937558 cram 35.6 GB
EGAF00000949172 cram 40.8 GB
EGAF00000952096 cram 43.1 GB
EGAF00000993092 cram 41.5 GB
EGAF00001005161 cram 39.4 GB
EGAF00001012707 cram 37.0 GB
EGAF00001012714 cram 39.1 GB
EGAF00001012754 cram 39.8 GB
EGAF00001014970 cram 39.1 GB
EGAF00001014978 cram 40.1 GB
EGAF00001017309 cram 37.8 GB
EGAF00001017793 cram 39.6 GB
EGAF00001017817 cram 41.3 GB
EGAF00001051102 cram 33.7 GB
EGAF00001051307 cram 37.7 GB
EGAF00001051309 cram 40.1 GB
EGAF00001051349 cram 42.6 GB
EGAF00001051352 cram 39.6 GB
EGAF00001051355 cram 34.4 GB
EGAF00001051357 cram 38.3 GB
EGAF00001073744 cram 39.3 GB
EGAF00001073767 cram 35.4 GB
EGAF00001085331 cram 41.6 GB
EGAF00001106288 cram 40.5 GB
EGAF00001109351 cram 36.6 GB
EGAF00001109572 cram 39.8 GB
EGAF00001110369 cram 35.4 GB
EGAF00001110374 cram 37.8 GB
EGAF00001143862 cram 36.7 GB
EGAF00001143866 cram 32.7 GB
EGAF00001143871 cram 35.4 GB
EGAF00001143877 cram 40.0 GB
EGAF00001144033 cram 35.6 GB
EGAF00001158690 cram 42.0 GB
EGAF00001158695 cram 37.9 GB
EGAF00001158945 cram 49.4 GB
EGAF00001158950 cram 38.6 GB
EGAF00001159315 cram 38.6 GB
EGAF00001159321 cram 39.5 GB
EGAF00001159324 cram 41.9 GB
EGAF00001161858 cram 38.4 GB
EGAF00001165037 cram 41.4 GB
EGAF00001165041 cram 37.3 GB
EGAF00001165043 cram 37.4 GB
EGAF00001165046 cram 42.2 GB
EGAF00001170996 cram 40.5 GB
EGAF00001171000 cram 37.2 GB
EGAF00001173287 cram 39.6 GB
EGAF00001173296 cram 39.1 GB
EGAF00001173308 cram 41.2 GB
EGAF00001173312 cram 40.6 GB
EGAF00001180200 cram 39.3 GB
EGAF00001180224 cram 41.3 GB
EGAF00001180331 cram 38.7 GB
EGAF00001180338 cram 38.2 GB
EGAF00001180342 cram 37.5 GB
EGAF00001180343 cram 37.9 GB
EGAF00001180431 cram 37.8 GB
EGAF00001180525 cram 36.5 GB
EGAF00001194524 cram 40.0 GB
EGAF00001194526 cram 38.6 GB
EGAF00001194528 cram 38.9 GB
EGAF00001194530 cram 38.8 GB
EGAF00001194615 cram 44.2 GB
EGAF00001194626 cram 42.5 GB
EGAF00001194644 cram 38.4 GB
EGAF00001194654 cram 37.4 GB
EGAF00001208744 cram 41.2 GB
EGAF00001208750 cram 40.5 GB
EGAF00001208795 cram 35.4 GB
EGAF00001208812 cram 32.7 GB
EGAF00001208829 cram 33.1 GB
EGAF00001208831 cram 33.4 GB
EGAF00001208834 cram 30.0 GB
EGAF00001208836 cram 34.8 GB
EGAF00001209060 cram 41.9 GB
EGAF00001209062 cram 42.1 GB
EGAF00001215059 cram 41.4 GB
EGAF00001215080 cram 38.0 GB
EGAF00001215086 cram 38.7 GB
EGAF00001215089 cram 39.4 GB
EGAF00001215093 cram 39.0 GB
EGAF00001215639 cram 40.6 GB
EGAF00001215652 cram 35.3 GB
EGAF00001215658 cram 37.8 GB
EGAF00001215664 cram 36.3 GB
EGAF00001215669 cram 36.3 GB
EGAF00001228434 cram 37.1 GB
EGAF00001228439 cram 36.5 GB
EGAF00001228495 cram 35.3 GB
EGAF00001233680 cram 37.8 GB
EGAF00001233682 cram 36.9 GB
EGAF00001237873 cram 35.0 GB
EGAF00001237881 cram 34.0 GB
EGAF00001237883 cram 34.4 GB
EGAF00001237894 cram 33.7 GB
EGAF00001237950 cram 40.0 GB
EGAF00001237953 cram 39.9 GB
EGAF00001237955 cram 39.1 GB
EGAF00001237976 cram 36.9 GB
EGAF00001238058 cram 35.1 GB
EGAF00001238070 cram 32.4 GB
EGAF00001271717 cram 37.5 GB
EGAF00001271719 cram 35.6 GB
EGAF00001271722 cram 35.7 GB
EGAF00001271726 cram 34.8 GB
EGAF00001273117 cram 33.1 GB
EGAF00001273122 cram 36.7 GB
EGAF00001274417 cram 37.7 GB
EGAF00001274421 cram 36.6 GB
EGAF00001299596 cram 35.4 GB
EGAF00001299618 cram 35.5 GB
EGAF00001342430 cram 35.3 GB
EGAF00001343672 cram 31.9 GB
EGAF00001348565 cram 31.8 GB
EGAF00001348575 cram 34.4 GB
EGAF00001348576 cram 42.5 GB
EGAF00001348578 cram 34.0 GB
EGAF00001348580 cram 33.4 GB
EGAF00001348582 cram 33.1 GB
EGAF00001348583 cram 37.1 GB
EGAF00001348584 cram 33.4 GB
EGAF00001348585 cram 31.7 GB
EGAF00001348589 cram 35.7 GB
EGAF00001348590 cram 35.2 GB
EGAF00001348591 cram 34.0 GB
EGAF00001348597 cram 33.1 GB
EGAF00001348598 cram 32.3 GB
EGAF00001348599 cram 32.6 GB
EGAF00001348605 cram 30.0 GB
EGAF00001381768 cram 34.9 GB
EGAF00001381775 cram 48.0 GB
EGAF00001396707 cram 42.6 GB
EGAF00001412923 cram 41.6 GB
EGAF00001414836 cram 40.0 GB
EGAF00001414837 cram 40.8 GB
EGAF00001414851 cram 40.2 GB
EGAF00001415186 cram 38.9 GB
EGAF00001415191 cram 41.5 GB
EGAF00001415199 cram 40.3 GB
EGAF00001415202 cram 43.2 GB
EGAF00001415206 cram 39.1 GB
EGAF00001415211 cram 40.7 GB
EGAF00001415216 cram 44.9 GB
EGAF00001415946 cram 42.3 GB
EGAF00001415951 cram 41.6 GB
EGAF00001415963 cram 39.1 GB
EGAF00001416486 cram 41.3 GB
EGAF00001416491 cram 42.1 GB
EGAF00001418946 cram 41.7 GB
EGAF00001418993 cram 42.6 GB
EGAF00001418996 cram 42.4 GB
EGAF00001419016 cram 40.5 GB
EGAF00001419017 cram 40.6 GB
EGAF00001419052 cram 43.8 GB
EGAF00001419065 cram 41.3 GB
EGAF00001419070 cram 39.0 GB
EGAF00001419071 cram 42.1 GB
EGAF00001419072 cram 40.1 GB
EGAF00001419079 cram 39.8 GB
EGAF00001419088 cram 41.7 GB
EGAF00001420473 cram 45.3 GB
EGAF00001433657 cram 38.9 GB
EGAF00001433665 cram 40.6 GB
EGAF00001433668 cram 37.5 GB
EGAF00001433703 cram 44.6 GB
EGAF00001433711 cram 40.6 GB
EGAF00001433715 cram 35.0 GB
EGAF00001433722 cram 44.8 GB
EGAF00001433725 cram 40.5 GB
EGAF00001433728 cram 48.9 GB
EGAF00001433731 cram 45.3 GB
EGAF00001433741 cram 40.2 GB
EGAF00001441686 cram 44.1 GB
EGAF00001441687 cram 43.9 GB
EGAF00001441689 cram 42.8 GB
EGAF00001441694 cram 44.9 GB
EGAF00001441695 cram 45.0 GB
EGAF00001554057 cram 37.6 GB
EGAF00001554081 cram 40.4 GB
EGAF00001554095 cram 36.9 GB
EGAF00001554121 cram 45.7 GB
371 Files (14.6 TB)