Why use it

Essential for estimating the incremental risk of autosomal recessive disorders in consanguineous couples above the general population background rate. Also useful for correlating with microarray AOH findings, detecting undisclosed consanguinity, and guiding expanded carrier screening decisions.

About

The Coefficient of Inbreeding (F) is the probability that both alleles at a given locus in an individual are identical by descent (IBD) — inherited from a single ancestral copy. It quantifies the degree to which a consanguineous mating increases the risk of homozygosity throughout the genome. The Coefficient of Relationship (R) between two individuals is the expected fraction of alleles shared IBD, and equals 2F for their offspring. Consanguinity increases the risk of autosomal recessive (AR) disorders by elevating the probability that both parents are carriers of the same ancestral recessive allele. On chromosomal microarray, the expected proportion of the genome showing Absence of Heterozygosity (AOH) is approximately equal to F.

When to use

Preconception or prenatal counseling for consanguineous couples
Pediatric evaluation of a child with multiple congenital anomalies, intellectual disability, or suspected recessive conditions
Interpreting chromosomal microarray results showing extensive regions of AOH (runs of homozygosity)
Estimating F when microarray AOH extent is known and comparing to declared relationship
Populations with high rates of consanguinity (Middle East, South Asia, North Africa, isolated communities)

Formula

Coefficient of Relationship (R) = ∑ (1/2)ⁿ where n = total path steps through each common ancestor Coefficient of Inbreeding (F) = R / 2 (F of offspring = half the R of parents) Expected AOH = F × genome size (3,000 Mb) For first cousins: R = 1/8, F = 1/16 = 6.25%

Pearls & pitfalls

F = 1/16 (6.25%) for first cousins — the offspring is expected to be homozygous by descent at 6.25% of loci (≈ 187 Mb of the 3 Gb genome).
Background risk of major congenital anomalies is ~2–3%; first-cousin union adds ~1.7–2.8% (ACOG, 2017).
A child of first cousins has a 1 in 16 chance that any given locus is homozygous by descent — not a 1 in 16 chance of being affected (disease risk also depends on having a pathogenic allele in the pedigree).
Multiple consanguineous loops in a pedigree are additive for F.
For non-paternity investigations: microarray AOH consistently >15% in an unrelated couple strongly suggests undisclosed consanguinity (F > ~0.06).
Populations: F ~0.01–0.04 is common in consanguineous communities; F ≥ 0.125 represents close consanguinity requiring referral.

Next steps

Correlate the calculated F with microarray AOH. If observed AOH significantly exceeds expected F, consider a closer unrecorded relationship or multiple consanguineous loops. Offer expanded carrier screening to both partners, prioritizing the most prevalent recessive disorders in the couple's ethnic background. For known recessive conditions in the family, offer targeted carrier testing first.

Evidence

Wright S. Coefficients of inbreeding and relationship. Am Nat. 1922;56:330-338. ACOG Practice Bulletin on Reproductive and Sexual Coercion (2013) and Preconception Care guidelines address consanguinity counseling. Risk data from Bennett et al. J Genet Couns. 2002. Supported by ACMG, ESHG, and BSGM guidelines.

References

Wright S. Coefficients of inbreeding and relationship. Am Nat. 1922;56:330-338.
Bennett RL et al. Genetic counseling and screening of consanguineous couples and their offspring. J Genet Couns. 2002;11(2):97-119. — link
ACOG Committee Opinion 762: Prepregnancy Counseling. Obstet Gynecol. 2019;133(1):e78-e89. — link
Hamamy H et al. Consanguineous marriages: recommendations from the International Workshop on Consanguinity. Genet Med. 2011;13(11):935-936. — link

Coefficient of Consanguinity & Inbreeding (F)

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