Leveraging Consanguinity In Pakistan to Uncover the Genomic Architecture of Alzheimer's Disease: Feasibility Study with ENIGMA-PAK
Enhancing Neuroimaging Genetics Through Meta Analysis in Pakistan (ENIGMA-PAK)’s objective is to implement genetic research for Alzheimer’s disease (AD) in Pakistan, where high rates of consanguinity may play an interesting role in Mendelian diseases such as Alzheimer’s Disease.
Alzheimer’s Disease (AD) accounts for 50-75% of all dementia cases, with more than half of these cases distributed throughout the low-middle income countries (LMIC). The projected growth of the world’s dementia population is said to increase from 58% to 68% by 2050. China, Pakistan, and neighboring South Asian and western Pacific countries show the fastest increase in their elderly populations. Despite various discoveries and advancements in Alzheimer's research, the lack of diversity calls for action. Close to 1.1 billion people live in consanguineous marriages, defined as a union between two individuals related as second cousins or closer. The prevalence of congenital anomalies in the offspring of first cousin marriages is about 1.7% - 2.8% higher than population risk, mostly due to autosomal rececssive diseases.
Current data is not representative of the population, as most data collected from Alzheimer’s research comes from North American and Western European countries. The National Institute on Aging (NIA) mobilized diversity efforts, creating the Alzheimer’s Disease Sequencing Project (ADSP) to better understand the complexities of AD. Since 2012, the ADSP has collected findings from ethnically diverse populations.
Enhancing Neuroimaging Genetics Through Meta Analysis in Pakistan (ENIGMA-PAK) team was established to contribute to ADSP efforts and advancements.
Our study team members at Aga Khan University (AKU) in Karachi, Pakistan are responsible for collecting blood, MRI scans, and phenotypic information from study participants. Study participants (including individuals with dementia, and health controls) are recruited from AKU Hospital, as well as the community in peri-urban sites. With the framework from the Longitudinal Aging Study in India- Diagnostic Assessment of Dementia (LASI-DAD), the ENIGMA-PAK study aligns with, and contributes to, ADSP’s goals in analyzing common and rare genetic variations.
This image shows a clinic located in one of the four peri-urban sites in Karachi, Pakistan. These sites include: Rehri Goth, Ibrahim Hyderi, Bhains Colony, and Ali Akbar Shah.
Image of ENIGMA-PAK Study Flyer.
Dr. Maheen Mausoof Adamson completed her Ph.D. in neuroscience from the University of Southern California and a postdoctoral fellowship in psychiatry and behavioral sciences at Stanford School of Medicine. She currently serves as Director of Research at the national Women’s Operational Military Exposure Network (WOMEN) center located at the War Related Illness and Injury Study Center (WRIISC), Senior Scientist at Rehabilitation Center at VA Palo Alto Healthcare System (VAPAHCS), and Clinical Professor (Affiliated) in the Department of Neurosurgery at Stanford University School of Medicine.
Dr. Adamson has over 15 years of experience directing large diverse teams to develop and implement several multi-site and longitudinal studies utilizing innovative tools for neuroimaging, neuromodulation, genetics, proteomics, and behavioral performance for improving the lives of adults with traumatic brain injuries, Alzheimer’s disease, pain, and depression. She serves as the Principal Investigator for the ENIGMA-PAK study.
Dr. Muhammad Parvaz is one of the Co-Investigators for the ENIGMA-PAK project. Dr. Parvaz is an Associate Professor for the Departments of Psychiatry, Neuroscience, and AI & Human Health at the Icahn School of Medicine at Mount Sinai, New York. Dr. Parvaz's primary research interest includes studying cognitive-affective interactions underlying deficits in motivation, reinforcement learning and inhibitory control in mental health disorders, specifically in substance use disorders, using behavioral, computational and neuroimaging techniques. For these studies, we use a comprehensive multimodal approach with multiscale modeling of exposomic (environmental, non-genetic factors), clinical (interviews and questionnaires), behavioral (cognitive tasks, speech, facial expressions), molecular (MR spectroscopy and blood based inflammatory markers), psychophysiological (EEG) and circuit-level (fMRI) biomarkers to precisely define the phenotype of interest and to track or predict clinical outcomes (e.g., development of substance use in adolescents and relapse in treatment seeking addicted individuals). He received his PhD at Stony Brook University, and has authored 70 publications.
Dr. Abdul Momin Kazi is an Assistant Professor and Clinical Epidemiologist at the Department of Paediatrics and Child Health at Aga Khan University in Karachi, with over 19 years of experience in public health surveillance. He holds an MBBS from Dow University, an MPH (Epidemiology) from Vanderbilt University, and is currently a PhD candidate at the University of British Columbia. He serves as Co-Principal Investigator and Site Principal Investigator of the CHAMPS Pakistan study and leads several research projects focused on vaccine-preventable diseases, child mortality, geospatial analysis, and mHealth interventions. Dr. Kazi has authored over 80 peer-reviewed publications, holds an h-index of 28, and has received more than 10,000 citations for his work.
Janice Le is a Clinical Research Administrative Assistant for the ENIGMA-PAK study, where she assists in organization and bridging communication. She is also a Research Assistant for the Adaptive Trial for the Treatment of Depressive Symptoms associated with Concussion using Repetitive Transcranial Magnetic Stimulation Protocols (ADEPT) study. Janice received her B.S. in Public Health from San Jose State University, where she discovered her interests in social epidemiology, community health, and biostatistics.
For more information about ENIGMA-PAK, please contact Janice via email here.
Dr. Li-San Wang serves as an Advisor/Collaborator for the ENIGMA-PAK Project. He achieved his B.S. and M.S. in Electrical Engineering at National Taiwan University in 1994 and 1996 respectively, and later achieved his Ph.D. in Computer Sciences at the University of Texas at Austin in 2003. Dr. Wang is currently the Co-Director at the Penn Neurodegenertation Genomics Center (PNGC) and Director of the Division of Diagnostic Innovation for the Department of Pathology and Laboratory Medicine.
His research interests include genetics of Alzheimer's Disease and Related Dementia, along with computational methods for big data in genomics research. At PNGC, their researchers apply high throughput genotyping and sequencing technologies to analyze tens of thousands of genomes and find novel genes. New experimental approaches, algorithms, and databases are developed in order to translate these findings into biological knowledge about the disease and new directions for drug discovery and preventive strategies.
Dr. Salman Kirmani is the Site Principal Investigator for ENIGMA-PAK. Dr. Salman Kirmani is a Medical Geneticist & Pediatric Endocrinologist associated with the Aga Khan University as a Professor of Paediatrics and Medicine, Chair for the Division of Women & Child Health, and Director of the Centre of Excellence for Women & Child Health. He is also the Interim Director of the Human Development Program at AKU. Dr. Kirmani achieved his MBBS (MD) from Dow Medical College, Karachi, followed by residency and fellowships from the Mayo School of Graduate Medical Education in Rochester, MN. Dr. Kirmani is certified by the American Board of Medical Genetics (Clinical Genetics) and the American Board of Paediatrics (General Paediatrics & Pediatric Endocrinology). He was on faculty at the Mayo Clinic until he returned to Pakistan to join the Aga Khan University in 2014.
Dr. Shireen Najam is a Pakistani board-certified general adult psychiatrist, interested in outcomes of neuropsychiatric disorders. She holds an MBBS and an FCPS. She is currently serving as a senior instructor at AKU, and Co-Investigator for the ENIGMA-PAK project.
Dr. Saqib Bakhshi graduated from Dow Medical College in 2013 and proceeded to complete his residency training in Neurosurgery at Aga Khan University (AKU) in Karachi, Pakistan. He graduated from the residency program in 2020 as the best graduate and researcher across all specialties. He has more than 90 research publications and has presented his work at national and international conferences. His clinical interests include pediatric neurosurgery and epilepsy surgery. He focuses his research on neurosurgery outcomes, medical education, and gender diversity in medicine. He is currently working as an Assistant Professor at AKU, and serves as one of the Co-Investigators for ENIGMA-PAK.
Aneeta Hotwani currently serves as Senior Manager at the Infectious Disease Research Laboratory in Aga Khan University’s Department of Pediatrics and Child Health. Her interests and expertise lie in, but are not limited to: bacteriology (typhoid fever, sepsis, etc.), breast milk macro/micronutrients, biobanking (freezer works), parasitology, and more. Aneeta serves as one of the Co-Investigators for the ENIGMA-PAK project. In addition, Aneeta is currently a Ph.D fellow, along with a M.S. in microbiology and a MBA in finance.
Dr. Nadia Fatima is an alumna of the Master of Health Policy and Management program at Aga Khan University and currently serves as a Research Specialist at the Centre of Excellence for Women and Child Health at Aga Khan University. Dr. Fatima is actively engaged in the ENIGMA-PAK project, where she is responsible for training the research team in screening, participant recruitment, and data collection. She supervises the team to ensure adherence to scientific and ethical standards across all study sites in peri-urban Karachi.
Dr. Paul Thompson is a Professor in the Keck School of Medicine of USC. His team’s research projects focus on the neuroscience, mathematics, computer science, software engineering and clinical aspects of neuroimaging and brain mapping. Honored with the 2023 Pioneer in Medicine Award of the Society of Brain Mapping and Therapeutics, and the U.S. Alzheimer Association’s Zenith Award, Paul Thompson directs the ENIGMA Consortium, a global alliance of 2500 scientists in 47 countries who conduct the largest studies of 30 major brain diseases – ranging from Parkinson’s disease, anorexia, schizophrenia, depression, ADHD, bipolar illness and OCD, to HIV and addictions and their effects in the brain. Collaborating with imaging labs around the world, Dr. Thompson and his students have published over 1,500 publications (h-index: 206) describing novel mathematical and computational strategies for analyzing brain image databases, for detecting pathology in individual patients and groups, and for creating disease-specific atlases of the human brain. Dr. Thompson acts as advisor/collaborator for the ENIGMA-PAK project.
Dr. Jinkook Lee is a Research Professor of Economics and the Program Director of Global Aging, Health, and Policy at the University of Southern California. Her research focuses on the economics of aging, with interdisciplinary training and expertise in large-scale population surveys. As the Principal Investigator on several NIH-funded grants, she laid the groundwork for studying Alzheimer’s Disease and Related Dementia and their risk factors and impacts in low and middle-income countries. She has developed the country’s first and only population-representative dementia study in India and helped develop sister studies in China, Kenya, Nepal, Pakistan, and Malawi. She provides scientific advice for WHO, OECD, World Bank, and Asia Development Bank and serves on the editorial boards for several scientific journals. She previously held a professorship at Ohio State University and the RAND Graduate School. She received her Ph.D. from Ohio State University and B.S. from Seoul National University. Dr. Lee serves as Co-Investigator for the ENIGMA-PAK study.
