# Leveraging consanguinity and homozygosity to identify novel recessive variants

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · 2021 · $600,000

## Abstract

PROJECT SUMMARY/ABSTRACT
Genome-wide association studies (GWAS) traditionally assume an additive model of
genetic inheritance, where the genetic effect of a heterozygous genotype is exactly
intermediate to the genetic effects of the two homozygous genotypes. However, we know
that many alleles act in either a dominant or recessive fashion. Detecting the phenotypic
effects of rare, recessive variants is especially challenging, due to the scarcity of rare,
homozygous genotypes. Here, we propose to use data from 96,000 individuals from the
Pakistan Genomic Resource (PGR) to quantify the effects of rare, recessive variants on a
wide range of phenotypic traits and common, complex diseases. Our study leverages the
high rates of inbreeding within the PGR (which increases the frequency of rare,
homozygous genotypes), as well as extensive lifestyle, family history and genetic data from
all participants. The specific aims for our project are (1) Phase and impute variants into
more than 96,000 PGR genomes using a reference panel that includes 6,200 high-
coverage genome sequences from South Asia; (2) Test for associations between a wide
range of phenotypes and genotype, using a combination of standard single-variant tests
and novel homozygosity-mapping approaches; and (3) Infer historical models of
consanguinity within the PGR, using the distributions of long runs of homozygosity (caused
by consanguineous marriages) both within and between individuals.

## Key facts

- **NIH application ID:** 10200877
- **Project number:** 5R01HG010689-03
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
- **Principal Investigator:** Danish Saleheen
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $600,000
- **Award type:** 5
- **Project period:** 2019-09-13 → 2023-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10200877

## Citation

> US National Institutes of Health, RePORTER application 10200877, Leveraging consanguinity and homozygosity to identify novel recessive variants (5R01HG010689-03). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10200877. Licensed CC0.

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