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Your search keyword '"Schoenherr, Sebastian"' showing total 2 results
Start Over Author "Schoenherr, Sebastian" Journal nature communications
2 results on '"Schoenherr, Sebastian"'

1. South Asian medical cohorts reveal strong founder effects and high rates of homozygosity

Author

Wall, Jeffrey D, Sathirapongsasuti, J Fah, Gupta, Ravi, Rasheed, Asif, Venkatesan, Radha, Belsare, Saurabh, Menon, Ramesh, Phalke, Sameer, Mittal, Anuradha, Fang, John, Tanneeru, Deepak, Deshmukh, Manjari, Bassi, Akshi, Robinson, Jacqueline, Chaudhary, Ruchi, Murugan, Sakthivel, ul-Asar, Zameer, Saleem, Imran, Ishtiaq, Unzila, Fatima, Areej, Sheikh, Saqib Shafi, Hameed, Shahid, Ishaq, Mohammad, Rasheed, Syed Zahed, Memon, Fazal-ur-Rehman, Jalal, Anjum, Abbas, Shahid, Frossard, Philippe, Fuchsberger, Christian, Forer, Lukas, Schoenherr, Sebastian, Bei, Qixin, Bhangale, Tushar, Tom, Jennifer, Gadde, Santosh Gopi Krishna, B V, Priya, Naik, Naveen Kumar, Wang, Minxian, Kwok, Pui-Yan, Khera, Amit V, Lakshmi, BR, Butterworth, Adam S, Chowdhury, Rajiv, Danesh, John, di Angelantonio, Emanuele, Naheed, Aliya, Goyal, Vinay, Kandadai, Rukmini M, Kumar, Hrishikesh, Borgohain, Rupam, Mukherjee, Adreesh, Wadia, Pettarusp M, Yadav, Ravi, Desai, Soaham, Kumar, Niraj, Biswas, Atanu, Pal, Pramod Kumar, Muthane, Uday B, Das, Shymal K, Ramprasad, Vedam L, Kukkle, Prashanth L, Seshagiri, Somasekar, Kathiresan, Sekar, Ghosh, Arkasubhra, Mohan, V, Saleheen, Danish, Stawiski, Eric W, and Peterson, Andrew S

Subjects
Genetics, Biotechnology, Clinical Research, Human Genome, Generic health relevance, Good Health and Well Being, Humans, Asian People, Bangladesh, Founder Effect, Homozygote, India, Pakistan, South Asian People
Abstract

The benefits of large-scale genetic studies for healthcare of the populations studied are well documented, but these genetic studies have traditionally ignored people from some parts of the world, such as South Asia. Here we describe whole genome sequence (WGS) data from 4806 individuals recruited from the healthcare delivery systems of Pakistan, India and Bangladesh, combined with WGS from 927 individuals from isolated South Asian populations. We characterize population structure in South Asia and describe a genotyping array (SARGAM) and imputation reference panel that are optimized for South Asian genomes. We find evidence for high rates of reproductive isolation, endogamy and consanguinity that vary across the subcontinent and that lead to levels of rare homozygotes that reach 100 times that seen in outbred populations. Founder effects increase the power to associate functional variants with disease processes and make South Asia a uniquely powerful place for population-scale genetic studies.

Published
2023

2. Loss-of-function genomic variants highlight potential therapeutic targets for cardiovascular disease.

Author

Nielsen, Jonas B, Rom, Oren, Surakka, Ida, Graham, Sarah E, Zhou, Wei, Roychowdhury, Tanmoy, Fritsche, Lars G, Gagliano Taliun, Sarah A, Sidore, Carlo, Liu, Yuhao, Gabrielsen, Maiken E, Skogholt, Anne Heidi, Wolford, Brooke, Overton, William, Zhao, Ying, Chen, Jin, Zhang, He, Hornsby, Whitney E, Acheampong, Akua, Grooms, Austen, Schaefer, Amanda, Zajac, Gregory JM, Villacorta, Luis, Zhang, Jifeng, Brumpton, Ben, Løset, Mari, Rai, Vivek, Lundegaard, Pia R, Olesen, Morten S, Taylor, Kent D, Palmer, Nicholette D, Chen, Yii-Der, Choi, Seung H, Lubitz, Steven A, Ellinor, Patrick T, Barnes, Kathleen C, Daya, Michelle, Rafaels, Nicholas, Weiss, Scott T, Lasky-Su, Jessica, Tracy, Russell P, Vasan, Ramachandran S, Cupples, L Adrienne, Mathias, Rasika A, Yanek, Lisa R, Becker, Lewis C, Peyser, Patricia A, Bielak, Lawrence F, Smith, Jennifer A, Aslibekyan, Stella, Hidalgo, Bertha A, Arnett, Donna K, Irvin, Marguerite R, Wilson, James G, Musani, Solomon K, Correa, Adolfo, Rich, Stephen S, Guo, Xiuqing, Rotter, Jerome I, Konkle, Barbara A, Johnsen, Jill M, Ashley-Koch, Allison E, Telen, Marilyn J, Sheehan, Vivien A, Blangero, John, Curran, Joanne E, Peralta, Juan M, Montgomery, Courtney, Sheu, Wayne H-H, Chung, Ren-Hua, Schwander, Karen, Nouraie, Seyed M, Gordeuk, Victor R, Zhang, Yingze, Kooperberg, Charles, Reiner, Alexander P, Jackson, Rebecca D, Bleecker, Eugene R, Meyers, Deborah A, Li, Xingnan, Das, Sayantan, Yu, Ketian, LeFaive, Jonathon, Smith, Albert, Blackwell, Tom, Taliun, Daniel, Zollner, Sebastian, Forer, Lukas, Schoenherr, Sebastian, Fuchsberger, Christian, Pandit, Anita, Zawistowski, Matthew, Kheterpal, Sachin, Brummett, Chad M, Natarajan, Pradeep, Schlessinger, David, Lee, Seunggeun, Kang, Hyun Min, Cucca, Francesco, and Holmen, Oddgeir L

Subjects
Liver, Humans, Cardiovascular Diseases, Lipids, Receptors, LDL, Gene Targeting, Gene Silencing, Genome, Human, Biological Specimen Banks, Genome-Wide Association Study, Molecular Targeted Therapy, United Kingdom, Loss of Function Mutation, Phenomics
Abstract

Pharmaceutical drugs targeting dyslipidemia and cardiovascular disease (CVD) may increase the risk of fatty liver disease and other metabolic disorders. To identify potential novel CVD drug targets without these adverse effects, we perform genome-wide analyses of participants in the HUNT Study in Norway (n = 69,479) to search for protein-altering variants with beneficial impact on quantitative blood traits related to cardiovascular disease, but without detrimental impact on liver function. We identify 76 (11 previously unreported) presumed causal protein-altering variants associated with one or more CVD- or liver-related blood traits. Nine of the variants are predicted to result in loss-of-function of the protein. This includes ZNF529:p.K405X, which is associated with decreased low-density-lipoprotein (LDL) cholesterol (P = 1.3 × 10-8) without being associated with liver enzymes or non-fasting blood glucose. Silencing of ZNF529 in human hepatoma cells results in upregulation of LDL receptor and increased LDL uptake in the cells. This suggests that inhibition of ZNF529 or its gene product should be prioritized as a novel candidate drug target for treating dyslipidemia and associated CVD.

Published
2020

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