genomics-pipeline

Step 11: Runs of Homozygosity (ROH) Analysis

What This Does

Detects long stretches of homozygous genotypes (autozygous segments) in the genome. These arise when both copies of a chromosomal region are inherited from a common ancestor.

Why

ROH analysis screens for consanguinity and uniparental disomy (UPD). Long ROH segments increase the risk of autosomal recessive disease by unmasking deleterious variants. ROH patterns also provide population-level ancestry information.

Tool

bcftools roh (samtools/bcftools)

Docker Image

staphb/bcftools:1.21

Command

SAMPLE=your_sample
GENOME_DIR=/path/to/your/data

docker run --rm \
  -v ${GENOME_DIR}/${SAMPLE}/vcf:/data \
  staphb/bcftools:1.21 \
  bcftools roh \
    --AF-dflt 0.4 \
    -o /data/${SAMPLE}_roh.txt \
    /data/${SAMPLE}.vcf.gz

# Output: ${GENOME_DIR}/${SAMPLE}/vcf/${SAMPLE}_roh.txt (tab-delimited ROH segments)

Interpretation

| Total ROH | Interpretation | |—|—| | <100 MB | Normal outbred population | | 100-300 MB | Possible distant consanguinity or population isolate | | >300 MB | Suggests close consanguinity (e.g., second cousins or closer) |

Individual ROH Segment	Interpretation
<1 MB	Common, population-level background
1-10 MB	Distant shared ancestry
>10 MB	Recent identity-by-descent (IBD), possible UPD if single chromosome

Important Notes

The script auto-detects chip data (no FORMAT/PL tag) and adds -G30 for genotype-only mode
--AF-dflt 0.4 sets a default allele frequency when population AF data is unavailable — suitable for single-sample WGS
Known false-positive regions (centromeric/pericentromeric, always appear as ROH in WGS):
- chr1: 125-143 MB
- chr9: 42-60 MB
- chr18: 15-20 MB
These centromeric artifacts should be excluded when calculating total ROH burden
A single large ROH (>20 MB) confined to one chromosome may indicate uniparental disomy — verify with SNP array or parental samples
ROH within known disease gene regions warrants checking for homozygous pathogenic variants

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