# Harmonized Diagnostic Assessment of Dementia (DAD) for Longitudinal Aging Study of India (LASI)-Genomic study

> **NIH NIH U01** · UNIVERSITY OF SOUTHERN CALIFORNIA · 2023 · $386,374

## Abstract

Summary
 Genetic factors play an important role in Alzheimer’s disease (AD), and there is evidence
that genes may play a bigger role in cognition as we age. Our preliminary analysis of the whole
genome sequences from LASI-DAD shows that our study has the most comprehensive survey of
genetic variation in South Asia. Further, we have uncovered that like most non-Africans, South
Asians have ~1-3% ancestry from archaic hominins––Neanderthals and Denisovans. Surveys of
Eurasians have shown that this history has played a critical role in shaping the genetic and
phenotypic variation in modern humans. For instance, archaic ancestry in Eurasians has impacted
numerous traits ranging from skin pigmentation to high altitude adaptation, and response to
SARS-CoV-2. However, most studies have focused on Europeans and East Asians, with very few
genomes from other parts of the world. Further, no study has investigated the role of archaic
ancestry in impacting the risk of Alzheimer’s disease or cognitive phenotypes.
 To fill this gap, we aim to investigate how archaic hominins (Neanderthal and Denisovan)
ancestry impacts the risk of Alzheimer’s disease and cognitive phenotypes in modern humans
using the large dataset of 2,700 samples from our LASI-DAD study. The LASI-DAD dataset
contains 2,700 individuals from diverse ethnolinguistic groups in India, with extensive phenotype
information for Alzheimer’s disease risk and cognitive phenotypes. The detailed genotype and
phenotype information from the LASI-DAD dataset provides a unique opportunity to study the
impact of Neanderthal, Denisovan and introgressed segments from other unknown hominins on
the health of present-day individuals and uncover introgressed genes associated with Alzheimer's
disease risk. Moreover, we are currently collecting more samples from additional regions and the
study is a very timely project as we can collect more samples from specific groups to increase our
power for genotype-phenotype analysis that show promising results.
 In this application, we propose the following specific aims: (1) to generate a map of archai
introgression in modern humans; (2) to perform association analysis to study the association of
Alzheimer’s disease risk and archaic ancestry; (3) to recruit samples from additional regions to
maximize its potential for future population genomics study.

## Key facts

- **NIH application ID:** 10836795
- **Project number:** 3U01AG064948-05S1
- **Recipient organization:** UNIVERSITY OF SOUTHERN CALIFORNIA
- **Principal Investigator:** Sharon L Kardia
- **Activity code:** U01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $386,374
- **Award type:** 3
- **Project period:** 2019-09-15 → 2026-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10836795

## Citation

> US National Institutes of Health, RePORTER application 10836795, Harmonized Diagnostic Assessment of Dementia (DAD) for Longitudinal Aging Study of India (LASI)-Genomic study (3U01AG064948-05S1). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10836795. Licensed CC0.

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