Pedigree Model

Overview

To support the interoperability of family health history data within and between existing standards (such as HL7 FHIR and Phenopackets), the GA4GH Clinical and PhenoTips Data Capture Workstream developed the Pedigree Conceptual Model.

The Pedigree Conceptual Model defines core classes and their properties, and is based on the A Recommendation for The Common Data Set for Family Health History.

Key Concepts

The model defines three core classes:

Individual

A person or entity.

  • Individual id - required

  • Sex at birth - required

  • Gender

  • Name

  • DOB

  • Age / Age Range / Estimated Age / Gestational Age

  • REA - Concept - suggested list of concepts from HANCESTRO

  • Deceased

  • Disease/condition: code, onset, contributed to death

  • Affected: Y/N/? - for backwards-compatibility with PED

  • Other risk-relevant observations

Relationship

A relationship that one individual has with another relative.

  • individual - required

  • relationship - required, coded using KIN terms

  • relative - required

Pedigree

A collection of information about related individuals and relationships between them.

  • ID - Required

  • Index patients (proband, consultand, first person tested positive for a particular condition/variant) - Individual - Type enum: Proband, Consultand, First Person Tested Positive

  • Completion status

  • Language

  • Narrative

  • Date collected/updated

Direction of Relationships

A Relationship defines a relationship between one individual and another, such as isBiologicalMotherOf or isTwinOf. Only one of the two directions needs to be specified, and it does not matter which.

Symmetric relationships are those where both individuals share the same relationship with one another. These include: isTwinOf and isPartnerOf.

Non-symmetric relationships are those where the relationship that individual X has to individual Y is not the same as the relationship that individual Y has to individual X. For example, if individual X has relationship isBiologicalParentOf to individual Y, then individual Y has relationship isBiologicalChildOf individual X.

Because of this inherent flexibility in the way that relationships can be described, we define the notion of a minimum standard form for describing a pedigree. A pedigree in minimum standard form: 1. Has explicit parent-child relationships between all parents and their offspring, and they are directed downwards, with the parent as the individual and the child as the relative. 2. Has sibling relationships only when this is not implied by having shared parents, and in the event of multiple siblings, all sibling relationships are defined relative to the same individual 3. Defines all twin relationships relative to the same individual 4. Has partnership relationships only when this is not implied by having shared children 5. Has extended relative relationships only when this is not implied by the previously-defined relationships, and they are directed downwards, with the ancestor as the individual and the descendant as the relative.

Compatible standards

Compatible standards provide an implementation guide for capturing and representing pedigree data in a manner that is compatible with this model.

The representation of each core data element within each standard is summarized in Classes.

The current list of compatible standards are:

Phenopackets

A Phenopacket implementation guide is currently underway. At the moment, an aligned implementation is defined on a branch of the Phenopacket repository: https://github.com/phenopackets/phenopacket-schema/blob/pedigree/src/main/proto/ga4gh/pedigree/v1/pedigree.proto

HL7 FHIR

The FHIR Implementation Guide is here: https://github.com/GA4GH-Pedigree-Standard/pedigree-fhir-ig

Examples

The following examples demonstrate the way in which pedigrees of various complexity can be represented using the pedigree model.

The precise representation within the context of one of the standards, such as FHIR or Phenopacket.

Basic Trio

A basic family trio consists of one male parent, one female parent, and a child. This would be represented as a Pedigree with three Individuals and two parent-child Relationships:

individuals:
  -
    id: MOTHER
    sex: FEMALE
  -
    id: FATHER
    sex: MALE
  -
    id: CHILD
    sex: UNKNOWN
relationships:
  -
    individual: MOTHER
    relationship: isBiologicalMotherOf
    relative: CHILD
  -
    individual: FATHER
    relationship: isBiologicalFatherOf
    relative: CHILD

Twins

The relationship between twins (TWIN1 and TWIN2) can be represented by adding another Individual, parent-child relationships and a twin Relationship to the Pedigree:

individuals:
  -
    id: MOTHER
    sex: FEMALE
  -
    id: FATHER
    sex: MALE
  -
    id: TWIN1
    sex: UNKNOWN
  -
    id: TWIN2
    sex: UNKNOWN
relationships:
  -
    individual: MOTHER
    relationship: isBiologicalMotherOf
    relative: CHILD
  -
    individual: FATHER
    relationship: isBiologicalFatherOf
    relative: CHILD
  -
    individual: TWIN1
    relationship: isMonozygoticTwinOf
    relative: TWIN2

The parent-child relationships for TWIN2 are not strictly necessary. Because the isMonozygoticTwinOf relationship is symmetric, it would be equally valid to have said that TWIN2 isMonozygoticTwinOf TWIN1.

Adoption

individuals:
  -
    id: MOTHER
    sex: FEMALE
  -
    id: BIOLOGICAL_MOTHER
    sex: FEMALE
  -
    id: FATHER
    sex: MALE
  -
    id: CHILD
    sex: UNKNOWN
relationships:
  -
    individual: MOTHER
    relationship: isAdoptiveParentOf
    relative: CHILD
  -
    individual: BIOLOGICAL_MOTHER
    relationship: isBiologicalMotherOf
    relative: CHILD
  -
    individual: FATHER
    relationship: isBiologicalFatherOf
    relative: CHILD

IVF

individuals:
  -
    id: MOTHER
    sex: FEMALE
  -
    id: SURROGATE
    sex: FEMALE
  -
    id: FATHER
    sex: MALE
  -
    id: CHILD
    sex: UNKNOWN
relationships:
  -
    individual: MOTHER
    relationship: isOvumDonorOf
    relative: CHILD
  -
    individual: SURROGATE
    relationship: isGestationalCarrierOf
    relative: CHILD
  -
    individual: FATHER
    relationship: isBiologicalFatherOf
    relative: CHILD

Complete cancer family

BRCA1 pedigree example

Example BRCA1 pedigree. Source: https://visualsonline.cancer.gov/details.cfm?imageid=10436

index:
  -
    id: 14
    type: proband
individuals:
  -
    id: 1
    sex: MALE
    deceased: true
  -
    id: 2
    sex: FEMALE
    deceased: true
  -
    id: 3
    sex: MALE
    deceased: true
  -
    id: 4
    sex: FEMALE
    deceased: true
    attributes:
      -
        term: Ovarian cancer
        ageAtDiagnosis: 49 yrs
  -
    id: 5
    sex: FEMALE
  -
    id: 6
    sex: FEMALE
  -
    id: 7
    sex: MALE
  -
    id: 8
    sex: FEMALE
    attributes:
      -
        term: Breast cancer
        ageAtDiagnosis: 42 yrs
  -
    id: 9
    sex: MALE
  -
    id: 10
    sex: FEMALE
  -
    id: 11
    sex: FEMALE
    attributes:
      -
        term: Ovarian cancer
        ageAtDiagnosis: 53 yrs
  -
    id: 12
    sex: FEMALE
  -
    id: 13
    sex: MALE
  -
    id: 14
    sex: FEMALE
  -
    id: 15
    sex: FEMALE
    attributes:
      -
        term: Breast cancer
        ageAtDiagnosis: 38 yrs
relationships:
  -
    individual: 1
    relationship: isBiologicalFatherOf
    relative: 5
  -
    individual: 2
    relationship: isBiologicalMotherOf
    relative: 5
  -
    individual: 1
    relationship: isBiologicalFatherOf
    relative: 6
  -
    individual: 2
    relationship: isBiologicalMotherOf
    relative: 6
  -
    individual: 1
    relationship: isBiologicalFatherOf
    relative: 7
  -
    individual: 2
    relationship: isBiologicalMotherOf
    relative: 7
  -
    individual: 3
    relationship: isBiologicalFatherOf
    relative: 8
  -
    individual: 4
    relationship: isBiologicalMotherOf
    relative: 8
  -
    individual: 3
    relationship: isBiologicalFatherOf
    relative: 9
  -
    individual: 4
    relationship: isBiologicalMotherOf
    relative: 9
  -
    individual: 3
    relationship: isBiologicalFatherOf
    relative: 11
  -
    individual: 4
    relationship: isBiologicalMotherOf
    relative: 11
  -
    individual: 3
    relationship: isBiologicalFatherOf
    relative: 12
  -
    individual: 4
    relationship: isBiologicalMotherOf
    relative: 12
  -
    individual: 7
    relationship: isBiologicalFatherOf
    relative: 13
  -
    individual: 8
    relationship: isBiologicalMotherOf
    relative: 13
  -
    individual: 9
    relationship: isBiologicalFatherOf
    relative: 14
  -
    individual: 10
    relationship: isBiologicalMotherOf
    relative: 14
  -
    individual: 7
    relationship: isBiologicalFatherOf
    relative: 15
  -
    individual: 8
    relationship: isBiologicalMotherOf
    relative: 15

Design motivations

Design motivation:

  • avoid overlap with other standards (fhir, phenopacket)

  • focus on relationship

  • graphical model, bringing relationships as top-level entities

  • allow for the synthesizing of patient-reported family history data, such as comes out of family history questionnaires and EHR records (and can be represented with the FamilyMemberHistoryResource), and support this information through to risk models

  • provide a standard interface for validation

  • facilitate conversion among existing standards for pedigree data

Relationships between individuals are standardized using concepts from the newly developed Kinship Ontology. To allow existing workflows and tools to gracefully add interoperability with this standard, we developed an open-source pedigree data interoperability library, pedigree-tools.