↓ Skip to main content

Exome Genotyping Identifies Pleiotropic Variants Associated with Red Blood Cell Traits

Overview of attention for article published in American Journal of Human Genetics, June 2016
Altmetric Badge

About this Attention Score

  • In the top 25% of all research outputs scored by Altmetric
  • High Attention Score compared to outputs of the same age (87th percentile)
  • Above-average Attention Score compared to outputs of the same age and source (62nd percentile)

Mentioned by

twitter
22 X users
facebook
1 Facebook page

Citations

dimensions_citation
62 Dimensions

Readers on

mendeley
169 Mendeley
citeulike
2 CiteULike
You are seeing a free-to-access but limited selection of the activity Altmetric has collected about this research output. Click here to find out more.
Title
Exome Genotyping Identifies Pleiotropic Variants Associated with Red Blood Cell Traits
Published in
American Journal of Human Genetics, June 2016
DOI 10.1016/j.ajhg.2016.05.007
Pubmed ID
Authors

Nathalie Chami, Ming-Huei Chen, Andrew J. Slater, John D. Eicher, Evangelos Evangelou, Salman M. Tajuddin, Latisha Love-Gregory, Tim Kacprowski, Ursula M. Schick, Akihiro Nomura, Ayush Giri, Samuel Lessard, Jennifer A. Brody, Claudia Schurmann, Nathan Pankratz, Lisa R. Yanek, Ani Manichaikul, Raha Pazoki, Evelin Mihailov, W. David Hill, Laura M. Raffield, Amber Burt, Traci M. Bartz, Diane M. Becker, Lewis C. Becker, Eric Boerwinkle, Jette Bork-Jensen, Erwin P. Bottinger, Michelle L. O’Donoghue, David R. Crosslin, Simon de Denus, Marie-Pierre Dubé, Paul Elliott, Gunnar Engström, Michele K. Evans, James S. Floyd, Myriam Fornage, He Gao, Andreas Greinacher, Vilmundur Gudnason, Torben Hansen, Tamara B. Harris, Caroline Hayward, Jussi Hernesniemi, Heather M. Highland, Joel N. Hirschhorn, Albert Hofman, Marguerite R. Irvin, Mika Kähönen, Ethan Lange, Lenore J. Launer, Terho Lehtimäki, Jin Li, David C.M. Liewald, Allan Linneberg, Yongmei Liu, Yingchang Lu, Leo-Pekka Lyytikäinen, Reedik Mägi, Rasika A. Mathias, Olle Melander, Andres Metspalu, Nina Mononen, Mike A. Nalls, Deborah A. Nickerson, Kjell Nikus, Chris J. O’Donnell, Marju Orho-Melander, Oluf Pedersen, Astrid Petersmann, Linda Polfus, Bruce M. Psaty, Olli T. Raitakari, Emma Raitoharju, Melissa Richard, Kenneth M. Rice, Fernando Rivadeneira, Jerome I. Rotter, Frank Schmidt, Albert Vernon Smith, John M. Starr, Kent D. Taylor, Alexander Teumer, Betina H. Thuesen, Eric S. Torstenson, Russell P. Tracy, Ioanna Tzoulaki, Neil A. Zakai, Caterina Vacchi-Suzzi, Cornelia M. van Duijn, Frank J.A. van Rooij, Mary Cushman, Ian J. Deary, Digna R. Velez Edwards, Anne-Claire Vergnaud, Lars Wallentin, Dawn M. Waterworth, Harvey D. White, James G. Wilson, Alan B. Zonderman, Sekar Kathiresan, Niels Grarup, Tõnu Esko, Ruth J.F. Loos, Leslie A. Lange, Nauder Faraday, Nada A. Abumrad, Todd L. Edwards, Santhi K. Ganesh, Paul L. Auer, Andrew D. Johnson, Alexander P. Reiner, Guillaume Lettre

Abstract

Red blood cell (RBC) traits are important heritable clinical biomarkers and modifiers of disease severity. To identify coding genetic variants associated with these traits, we conducted meta-analyses of seven RBC phenotypes in 130,273 multi-ethnic individuals from studies genotyped on an exome array. After conditional analyses and replication in 27,480 independent individuals, we identified 16 new RBC variants. We found low-frequency missense variants in MAP1A (rs55707100, minor allele frequency [MAF] = 3.3%, p = 2 × 10(-10) for hemoglobin [HGB]) and HNF4A (rs1800961, MAF = 2.4%, p < 3 × 10(-8) for hematocrit [HCT] and HGB). In African Americans, we identified a nonsense variant in CD36 associated with higher RBC distribution width (rs3211938, MAF = 8.7%, p = 7 × 10(-11)) and showed that it is associated with lower CD36 expression and strong allelic imbalance in ex vivo differentiated human erythroblasts. We also identified a rare missense variant in ALAS2 (rs201062903, MAF = 0.2%) associated with lower mean corpuscular volume and mean corpuscular hemoglobin (p < 8 × 10(-9)). Mendelian mutations in ALAS2 are a cause of sideroblastic anemia and erythropoietic protoporphyria. Gene-based testing highlighted three rare missense variants in PKLR, a gene mutated in Mendelian non-spherocytic hemolytic anemia, associated with HGB and HCT (SKAT p < 8 × 10(-7)). These rare, low-frequency, and common RBC variants showed pleiotropy, being also associated with platelet, white blood cell, and lipid traits. Our association results and functional annotation suggest the involvement of new genes in human erythropoiesis. We also confirm that rare and low-frequency variants play a role in the architecture of complex human traits, although their phenotypic effect is generally smaller than originally anticipated.

X Demographics

X Demographics

The data shown below were collected from the profiles of 22 X users who shared this research output. Click here to find out more about how the information was compiled.
Mendeley readers

Mendeley readers

The data shown below were compiled from readership statistics for 169 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
United Kingdom 1 <1%
Spain 1 <1%
Sweden 1 <1%
Switzerland 1 <1%
Unknown 165 98%

Demographic breakdown

Readers by professional status Count As %
Researcher 28 17%
Student > Ph. D. Student 23 14%
Student > Master 18 11%
Student > Bachelor 13 8%
Other 11 7%
Other 36 21%
Unknown 40 24%
Readers by discipline Count As %
Medicine and Dentistry 41 24%
Biochemistry, Genetics and Molecular Biology 28 17%
Agricultural and Biological Sciences 13 8%
Nursing and Health Professions 6 4%
Computer Science 4 2%
Other 26 15%
Unknown 51 30%
Attention Score in Context

Attention Score in Context

This research output has an Altmetric Attention Score of 14. 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 20 May 2017.
All research outputs
#2,549,203
of 25,374,917 outputs
Outputs from American Journal of Human Genetics
#1,361
of 5,879 outputs
Outputs of similar age
#44,759
of 368,655 outputs
Outputs of similar age from American Journal of Human Genetics
#26
of 70 outputs
Altmetric has tracked 25,374,917 research outputs across all sources so far. Compared to these this one has done well and is in the 89th percentile: it's in the top 25% of all research outputs ever tracked by Altmetric.
So far Altmetric has tracked 5,879 research outputs from this source. They typically receive a lot more attention than average, with a mean Attention Score of 18.3. This one has done well, scoring higher than 76% 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 368,655 tracked outputs that were published within six weeks on either side of this one in any source. This one has done well, scoring higher than 87% of its contemporaries.
We're also able to compare this research output to 70 others from the same source and published within six weeks on either side of this one. This one has gotten more attention than average, scoring higher than 62% of its contemporaries.