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4 results on '"Unzila Ishtiaq"'

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

Author

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

Subjects
Science
Abstract

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
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2. Genome-wide analysis of blood lipid metabolites in over 5000 South Asians reveals biological insights at cardiometabolic disease loci

Author

Eric L. Harshfield, Eric B. Fauman, David Stacey, Dirk S. Paul, Daniel Ziemek, Rachel M. Y. Ong, John Danesh, Adam S. Butterworth, Asif Rasheed, Taniya Sattar, Zameer-ul-Asar, Imran Saleem, Zoubia Hina, Unzila Ishtiaq, Nadeem Qamar, Nadeem Hayat Mallick, Zia Yaqub, Tahir Saghir, Syed Nadeem Hasan Rizvi, Anis Memon, Mohammad Ishaq, Syed Zahed Rasheed, Fazal-ur-Rehman Memon, Anjum Jalal, Shahid Abbas, Philippe Frossard, Danish Saleheen, Angela M. Wood, Julian L. Griffin, and Albert Koulman

Subjects
Lipidomics, Genetics, Gaussian Graphical Modelling, Network analysis, South Asian, Medicine
Abstract

Abstract Background Genetic, lifestyle, and environmental factors can lead to perturbations in circulating lipid levels and increase the risk of cardiovascular and metabolic diseases. However, how changes in individual lipid species contribute to disease risk is often unclear. Moreover, little is known about the role of lipids on cardiovascular disease in Pakistan, a population historically underrepresented in cardiovascular studies. Methods We characterised the genetic architecture of the human blood lipidome in 5662 hospital controls from the Pakistan Risk of Myocardial Infarction Study (PROMIS) and 13,814 healthy British blood donors from the INTERVAL study. We applied a candidate causal gene prioritisation tool to link the genetic variants associated with each lipid to the most likely causal genes, and Gaussian Graphical Modelling network analysis to identify and illustrate relationships between lipids and genetic loci. Results We identified 253 genetic associations with 181 lipids measured using direct infusion high-resolution mass spectrometry in PROMIS, and 502 genetic associations with 244 lipids in INTERVAL. Our analyses revealed new biological insights at genetic loci associated with cardiometabolic diseases, including novel lipid associations at the LPL, MBOAT7, LIPC, APOE-C1-C2-C4, SGPP1, and SPTLC3 loci. Conclusions Our findings, generated using a distinctive lipidomics platform in an understudied South Asian population, strengthen and expand the knowledge base of the genetic determinants of lipids and their association with cardiometabolic disease-related loci.

Published
2021
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3. Genome-wide analysis of blood lipid metabolites in over 5000 South Asians reveals biological insights at cardiometabolic disease loci

Author

Zoubia Hina, Julian L. Griffin, Asif Rasheed, Nadeem Qamar, Danish Saleheen, Dirk S. Paul, Imran Saleem, Taniya Sattar, M. Ishaq, Nadeem Hayat Mallick, Adam S. Butterworth, Philippe M. Frossard, Daniel Ziemek, Fazal-ur-Rehman Memon, Syed Nadeem Hasan Rizvi, Albert Koulman, Anjum Jalal, Tahir Saghir, John Danesh, Angela M. Wood, David Stacey, Eric B. Fauman, Unzila Ishtiaq, Anis Memon, Rachel M. Y. Ong, Eric L. Harshfield, Shahid Abbas, Zameer-ul-Asar, Zia Yaqub, Syed Zahed Rasheed, Harshfield, Eric [0000-0001-8767-0928], Paul, Dirk [0000-0002-8230-0116], Danesh, John [0000-0003-1158-6791], Butterworth, Adam [0000-0002-6915-9015], Wood, Angela [0000-0002-7937-304X], Koulman, Albert [0000-0001-9998-051X], Apollo - University of Cambridge Repository, and Paul, Dirk S [0000-0002-8230-0116]

Subjects
South asia, Population, Myocardial Infarction, Blood lipids, Disease, Gaussian Graphical Modelling, Polymorphism, Single Nucleotide, White People, 03 medical and health sciences, 0302 clinical medicine, Asian People, Lipidomics, Genetics, Medicine, South Asian, Humans, Genetic Predisposition to Disease, education, Gene, 030304 developmental biology, 0303 health sciences, education.field_of_study, business.industry, General Medicine, Lipidome, Lipids, Genetic architecture, 3. Good health, Network analysis, business, 030217 neurology & neurosurgery, Research Article, Genome-Wide Association Study
Abstract

Background Genetic, lifestyle, and environmental factors can lead to perturbations in circulating lipid levels and increase the risk of cardiovascular and metabolic diseases. However, how changes in individual lipid species contribute to disease risk is often unclear. Moreover, little is known about the role of lipids on cardiovascular disease in Pakistan, a population historically underrepresented in cardiovascular studies. Methods We characterised the genetic architecture of the human blood lipidome in 5662 hospital controls from the Pakistan Risk of Myocardial Infarction Study (PROMIS) and 13,814 healthy British blood donors from the INTERVAL study. We applied a candidate causal gene prioritisation tool to link the genetic variants associated with each lipid to the most likely causal genes, and Gaussian Graphical Modelling network analysis to identify and illustrate relationships between lipids and genetic loci. Results We identified 253 genetic associations with 181 lipids measured using direct infusion high-resolution mass spectrometry in PROMIS, and 502 genetic associations with 244 lipids in INTERVAL. Our analyses revealed new biological insights at genetic loci associated with cardiometabolic diseases, including novel lipid associations at the LPL, MBOAT7, LIPC, APOE-C1-C2-C4, SGPP1, and SPTLC3 loci. Conclusions Our findings, generated using a distinctive lipidomics platform in an understudied South Asian population, strengthen and expand the knowledge base of the genetic determinants of lipids and their association with cardiometabolic disease-related loci.

Published
2021

4. Genome-wide analysis of blood lipid metabolites in over 5,000 South Asians reveals biological insights at cardiometabolic disease loci

Author

Unzila Ishtiaq, Dirk S. Paul, Zoubia Hina, Philippe M. Frossard, Danish Saleheen, Eric B. Fauman, Syed Nadeem Hasan Rizvi, Rachel M. Y. Ong, Nadeem Hayat Mallick, Syed Zahed Rasheed, Eric L. Harshfield, Angela M. Wood, Taniya Sattar, John Danesh, Fazal-ur-Rehman Memon, David Stacey, Shahid Abbas, Zameer-ul-Asar, Anis Memon, Zia Yaqub, Imran Saleem, Asif Rasheed, Albert Koulman, Anjum Jalal, M. Ishaq, Tahir Saghir, Adam S. Butterworth, Daniel Ziemek, Julian L. Griffin, and Nadeem Qamar

Subjects
Genetics, education.field_of_study, South asia, Population, Lipidomics, Blood lipids, Disease, Lipidome, Biology, education, Gene, Genetic architecture
Abstract

BackgroundGenetic, lifestyle, and environmental factors can lead to perturbations in circulating lipid levels and increase risk of cardiovascular and metabolic diseases. However, how changes in individual lipid species contribute to disease risk is often unclear. Moreover, little is known about the role of lipids on cardiovascular disease in Pakistan, a population historically underrepresented in cardiovascular studies.MethodsWe characterised the genetic architecture of the human blood lipidome in 5,662 hospital controls from the Pakistan Risk of Myocardial Infarction Study (PROMIS) and 13,814 healthy British blood donors from the INTERVAL study. We applied a candidate causal gene prioritisation tool to link the genetic variants associated with each lipid to the most likely causal genes, and Gaussian Graphical Modelling network analysis to identify and illustrate relationships between lipids and genetic loci.ResultsWe identified 359 genetic associations with 255 lipids measured using direct infusion high-resolution mass spectrometry in PROMIS, and 616 genetic associations with 326 lipids in INTERVAL. Our analyses revealed new biological insights at genetic loci associated with cardiometabolic diseases, including novel lipid associations at the LPL, MBOAT7, LIPC, APOE-C1-C2-C4, SGPP1, and SPTLC3 loci.ConclusionsOur findings, generated using a distinctive lipidomics platform in an understudied South Asian population, strengthen and expand the knowledge base of the genetic determinants of lipids and their association with cardiometabolic disease-related loci.

Published
2020
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