Genome-wide polygenic scores for common diseases identify individuals with risk equivalent to monogenic mutations View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2018-08-13

AUTHORS

Amit V. Khera, Mark Chaffin, Krishna G. Aragam, Mary E. Haas, Carolina Roselli, Seung Hoan Choi, Pradeep Natarajan, Eric S. Lander, Steven A. Lubitz, Patrick T. Ellinor, Sekar Kathiresan

ABSTRACT

A key public health need is to identify individuals at high risk for a given disease to enable enhanced screening or preventive therapies. Because most common diseases have a genetic component, one important approach is to stratify individuals based on inherited DNA variation1. Proposed clinical applications have largely focused on finding carriers of rare monogenic mutations at several-fold increased risk. Although most disease risk is polygenic in nature2–5, it has not yet been possible to use polygenic predictors to identify individuals at risk comparable to monogenic mutations. Here, we develop and validate genome-wide polygenic scores for five common diseases. The approach identifies 8.0, 6.1, 3.5, 3.2, and 1.5% of the population at greater than threefold increased risk for coronary artery disease, atrial fibrillation, type 2 diabetes, inflammatory bowel disease, and breast cancer, respectively. For coronary artery disease, this prevalence is 20-fold higher than the carrier frequency of rare monogenic mutations conferring comparable risk6. We propose that it is time to contemplate the inclusion of polygenic risk prediction in clinical care, and discuss relevant issues. More... »

PAGES

1219-1224

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/s41588-018-0183-z

DOI

http://dx.doi.org/10.1038/s41588-018-0183-z

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1106070346

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/30104762


Indexing Status Check whether this publication has been indexed by Scopus and Web Of Science using the SN Indexing Status Tool
Incoming Citations Browse incoming citations for this publication using opencitations.net

JSON-LD is the canonical representation for SciGraph data.

TIP: You can open this SciGraph record using an external JSON-LD service: JSON-LD Playground Google SDTT

[
  {
    "@context": "https://springernature.github.io/scigraph/jsonld/sgcontext.json", 
    "about": [
      {
        "id": "http://purl.org/au-research/vocabulary/anzsrc-for/2008/06", 
        "inDefinedTermSet": "http://purl.org/au-research/vocabulary/anzsrc-for/2008/", 
        "name": "Biological Sciences", 
        "type": "DefinedTerm"
      }, 
      {
        "id": "http://purl.org/au-research/vocabulary/anzsrc-for/2008/0604", 
        "inDefinedTermSet": "http://purl.org/au-research/vocabulary/anzsrc-for/2008/", 
        "name": "Genetics", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Adult", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Aged", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Disease", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Female", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Genetic Predisposition to Disease", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Genome-Wide Association Study", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Humans", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Male", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Middle Aged", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Multifactorial Inheritance", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Mutation", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Polymorphism, Single Nucleotide", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Risk Factors", 
        "type": "DefinedTerm"
      }
    ], 
    "author": [
      {
        "affiliation": {
          "alternateName": "Cardiovascular Disease Initiative of the Broad Institute of Harvard and MIT, Cambridge, MA, USA", 
          "id": "http://www.grid.ac/institutes/grid.66859.34", 
          "name": [
            "Center for Genomic Medicine, Massachusetts General Hospital, Boston, MA, USA", 
            "Cardiology Division of the Department of Medicine, Massachusetts General Hospital, Boston, MA, USA", 
            "Harvard Medical School, Boston, MA, USA", 
            "Cardiovascular Disease Initiative of the Broad Institute of Harvard and MIT, Cambridge, MA, USA"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Khera", 
        "givenName": "Amit V.", 
        "id": "sg:person.07374640413.24", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.07374640413.24"
        ], 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "Cardiovascular Disease Initiative of the Broad Institute of Harvard and MIT, Cambridge, MA, USA", 
          "id": "http://www.grid.ac/institutes/grid.66859.34", 
          "name": [
            "Cardiovascular Disease Initiative of the Broad Institute of Harvard and MIT, Cambridge, MA, USA"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Chaffin", 
        "givenName": "Mark", 
        "id": "sg:person.014110301753.77", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.014110301753.77"
        ], 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "Cardiovascular Disease Initiative of the Broad Institute of Harvard and MIT, Cambridge, MA, USA", 
          "id": "http://www.grid.ac/institutes/grid.66859.34", 
          "name": [
            "Center for Genomic Medicine, Massachusetts General Hospital, Boston, MA, USA", 
            "Cardiology Division of the Department of Medicine, Massachusetts General Hospital, Boston, MA, USA", 
            "Harvard Medical School, Boston, MA, USA", 
            "Cardiovascular Disease Initiative of the Broad Institute of Harvard and MIT, Cambridge, MA, USA"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Aragam", 
        "givenName": "Krishna G.", 
        "id": "sg:person.01117710630.56", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01117710630.56"
        ], 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "Cardiovascular Disease Initiative of the Broad Institute of Harvard and MIT, Cambridge, MA, USA", 
          "id": "http://www.grid.ac/institutes/grid.66859.34", 
          "name": [
            "Cardiovascular Disease Initiative of the Broad Institute of Harvard and MIT, Cambridge, MA, USA"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Haas", 
        "givenName": "Mary E.", 
        "id": "sg:person.0653567411.03", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0653567411.03"
        ], 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "Cardiovascular Disease Initiative of the Broad Institute of Harvard and MIT, Cambridge, MA, USA", 
          "id": "http://www.grid.ac/institutes/grid.66859.34", 
          "name": [
            "Cardiovascular Disease Initiative of the Broad Institute of Harvard and MIT, Cambridge, MA, USA"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Roselli", 
        "givenName": "Carolina", 
        "id": "sg:person.07454351775.50", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.07454351775.50"
        ], 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "Cardiovascular Disease Initiative of the Broad Institute of Harvard and MIT, Cambridge, MA, USA", 
          "id": "http://www.grid.ac/institutes/grid.66859.34", 
          "name": [
            "Cardiovascular Disease Initiative of the Broad Institute of Harvard and MIT, Cambridge, MA, USA"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Choi", 
        "givenName": "Seung Hoan", 
        "id": "sg:person.0773123264.12", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0773123264.12"
        ], 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "Cardiovascular Disease Initiative of the Broad Institute of Harvard and MIT, Cambridge, MA, USA", 
          "id": "http://www.grid.ac/institutes/grid.66859.34", 
          "name": [
            "Cardiology Division of the Department of Medicine, Massachusetts General Hospital, Boston, MA, USA", 
            "Harvard Medical School, Boston, MA, USA", 
            "Cardiovascular Disease Initiative of the Broad Institute of Harvard and MIT, Cambridge, MA, USA"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Natarajan", 
        "givenName": "Pradeep", 
        "id": "sg:person.01120503505.13", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01120503505.13"
        ], 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "Cardiovascular Disease Initiative of the Broad Institute of Harvard and MIT, Cambridge, MA, USA", 
          "id": "http://www.grid.ac/institutes/grid.66859.34", 
          "name": [
            "Cardiovascular Disease Initiative of the Broad Institute of Harvard and MIT, Cambridge, MA, USA"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Lander", 
        "givenName": "Eric S.", 
        "id": "sg:person.01260666165.62", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01260666165.62"
        ], 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "Cardiovascular Disease Initiative of the Broad Institute of Harvard and MIT, Cambridge, MA, USA", 
          "id": "http://www.grid.ac/institutes/grid.66859.34", 
          "name": [
            "Cardiology Division of the Department of Medicine, Massachusetts General Hospital, Boston, MA, USA", 
            "Harvard Medical School, Boston, MA, USA", 
            "Cardiovascular Disease Initiative of the Broad Institute of Harvard and MIT, Cambridge, MA, USA"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Lubitz", 
        "givenName": "Steven A.", 
        "id": "sg:person.01270001061.21", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01270001061.21"
        ], 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "Cardiovascular Disease Initiative of the Broad Institute of Harvard and MIT, Cambridge, MA, USA", 
          "id": "http://www.grid.ac/institutes/grid.66859.34", 
          "name": [
            "Cardiology Division of the Department of Medicine, Massachusetts General Hospital, Boston, MA, USA", 
            "Harvard Medical School, Boston, MA, USA", 
            "Cardiovascular Disease Initiative of the Broad Institute of Harvard and MIT, Cambridge, MA, USA"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Ellinor", 
        "givenName": "Patrick T.", 
        "id": "sg:person.01300106701.65", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01300106701.65"
        ], 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "Cardiovascular Disease Initiative of the Broad Institute of Harvard and MIT, Cambridge, MA, USA", 
          "id": "http://www.grid.ac/institutes/grid.66859.34", 
          "name": [
            "Center for Genomic Medicine, Massachusetts General Hospital, Boston, MA, USA", 
            "Cardiology Division of the Department of Medicine, Massachusetts General Hospital, Boston, MA, USA", 
            "Harvard Medical School, Boston, MA, USA", 
            "Cardiovascular Disease Initiative of the Broad Institute of Harvard and MIT, Cambridge, MA, USA"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Kathiresan", 
        "givenName": "Sekar", 
        "id": "sg:person.0767751267.74", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0767751267.74"
        ], 
        "type": "Person"
      }
    ], 
    "citation": [
      {
        "id": "sg:pub.10.1186/s13742-015-0047-8", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1037894462", 
          "https://doi.org/10.1186/s13742-015-0047-8"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1038/ng.3359", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1019843926", 
          "https://doi.org/10.1038/ng.3359"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1038/nn.4404", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1018996868", 
          "https://doi.org/10.1038/nn.4404"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1038/nature18642", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1036558635", 
          "https://doi.org/10.1038/nature18642"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1038/nature24284", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1092349555", 
          "https://doi.org/10.1038/nature24284"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1038/ng.3843", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1084863147", 
          "https://doi.org/10.1038/ng.3843"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1038/nature15393", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1021812064", 
          "https://doi.org/10.1038/nature15393"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1038/nature19057", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1022281897", 
          "https://doi.org/10.1038/nature19057"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1038/nature09764", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1037658930", 
          "https://doi.org/10.1038/nature09764"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1038/s41588-018-0193-x", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1106026183", 
          "https://doi.org/10.1038/s41588-018-0193-x"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1038/nrg3118", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1001779725", 
          "https://doi.org/10.1038/nrg3118"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1038/ng.2579", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1020935195", 
          "https://doi.org/10.1038/ng.2579"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1038/ng.3396", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1034378235", 
          "https://doi.org/10.1038/ng.3396"
        ], 
        "type": "CreativeWork"
      }
    ], 
    "datePublished": "2018-08-13", 
    "datePublishedReg": "2018-08-13", 
    "description": "A key public health need is to identify individuals at high risk for a given disease to enable enhanced screening or preventive therapies. Because most common diseases have a genetic component, one important approach is to stratify individuals based on inherited DNA variation1. Proposed clinical applications have largely focused on finding carriers of rare monogenic mutations at several-fold increased risk. Although most disease risk is polygenic in nature2\u20135, it has not yet been possible to use polygenic predictors to identify individuals at risk comparable to monogenic mutations. Here, we develop and validate genome-wide polygenic scores for five common diseases. The approach identifies 8.0, 6.1, 3.5, 3.2, and 1.5% of the population at greater than threefold increased risk for coronary artery disease, atrial fibrillation, type 2 diabetes, inflammatory bowel disease, and breast cancer, respectively. For coronary artery disease, this prevalence is 20-fold higher than the carrier frequency of rare monogenic mutations conferring comparable risk6. We propose that it is time to contemplate the inclusion of polygenic risk prediction in clinical care, and discuss relevant issues.", 
    "genre": "article", 
    "id": "sg:pub.10.1038/s41588-018-0183-z", 
    "isAccessibleForFree": true, 
    "isFundedItemOf": [
      {
        "id": "sg:grant.7171348", 
        "type": "MonetaryGrant"
      }, 
      {
        "id": "sg:grant.2419858", 
        "type": "MonetaryGrant"
      }, 
      {
        "id": "sg:grant.2542084", 
        "type": "MonetaryGrant"
      }, 
      {
        "id": "sg:grant.2421237", 
        "type": "MonetaryGrant"
      }, 
      {
        "id": "sg:grant.8472499", 
        "type": "MonetaryGrant"
      }, 
      {
        "id": "sg:grant.4730138", 
        "type": "MonetaryGrant"
      }, 
      {
        "id": "sg:grant.2423351", 
        "type": "MonetaryGrant"
      }, 
      {
        "id": "sg:grant.3537179", 
        "type": "MonetaryGrant"
      }, 
      {
        "id": "sg:grant.3933199", 
        "type": "MonetaryGrant"
      }, 
      {
        "id": "sg:grant.2684605", 
        "type": "MonetaryGrant"
      }, 
      {
        "id": "sg:grant.4242960", 
        "type": "MonetaryGrant"
      }, 
      {
        "id": "sg:grant.7211970", 
        "type": "MonetaryGrant"
      }
    ], 
    "isPartOf": [
      {
        "id": "sg:journal.1103138", 
        "issn": [
          "1061-4036", 
          "1546-1718"
        ], 
        "name": "Nature Genetics", 
        "publisher": "Springer Nature", 
        "type": "Periodical"
      }, 
      {
        "issueNumber": "9", 
        "type": "PublicationIssue"
      }, 
      {
        "type": "PublicationVolume", 
        "volumeNumber": "50"
      }
    ], 
    "keywords": [
      "rare monogenic mutations", 
      "coronary artery disease", 
      "artery disease", 
      "common disease", 
      "monogenic mutations", 
      "inflammatory bowel disease", 
      "type 2 diabetes", 
      "public health needs", 
      "preventive therapy", 
      "bowel disease", 
      "atrial fibrillation", 
      "breast cancer", 
      "clinical care", 
      "high risk", 
      "most disease risk", 
      "health needs", 
      "disease risk", 
      "disease", 
      "genome-wide polygenic scores", 
      "polygenic predictors", 
      "risk prediction", 
      "most common diseases", 
      "clinical application", 
      "risk", 
      "enhanced screening", 
      "polygenic scores", 
      "scores", 
      "mutations", 
      "individuals", 
      "genetic component", 
      "diabetes", 
      "fibrillation", 
      "therapy", 
      "cancer", 
      "prevalence", 
      "polygenic risk prediction", 
      "care", 
      "predictors", 
      "screening", 
      "RISK6", 
      "population", 
      "important approach", 
      "relevant issues", 
      "need", 
      "frequency", 
      "carriers", 
      "inclusion", 
      "time", 
      "approach", 
      "components", 
      "carrier frequency", 
      "issues", 
      "prediction", 
      "applications"
    ], 
    "name": "Genome-wide polygenic scores for common diseases identify individuals with risk equivalent to monogenic mutations", 
    "pagination": "1219-1224", 
    "productId": [
      {
        "name": "dimensions_id", 
        "type": "PropertyValue", 
        "value": [
          "pub.1106070346"
        ]
      }, 
      {
        "name": "doi", 
        "type": "PropertyValue", 
        "value": [
          "10.1038/s41588-018-0183-z"
        ]
      }, 
      {
        "name": "pubmed_id", 
        "type": "PropertyValue", 
        "value": [
          "30104762"
        ]
      }
    ], 
    "sameAs": [
      "https://doi.org/10.1038/s41588-018-0183-z", 
      "https://app.dimensions.ai/details/publication/pub.1106070346"
    ], 
    "sdDataset": "articles", 
    "sdDatePublished": "2022-11-24T21:02", 
    "sdLicense": "https://scigraph.springernature.com/explorer/license/", 
    "sdPublisher": {
      "name": "Springer Nature - SN SciGraph project", 
      "type": "Organization"
    }, 
    "sdSource": "s3://com-springernature-scigraph/baseset/20221124/entities/gbq_results/article/article_762.jsonl", 
    "type": "ScholarlyArticle", 
    "url": "https://doi.org/10.1038/s41588-018-0183-z"
  }
]
 

Download the RDF metadata as:  json-ld nt turtle xml License info

HOW TO GET THIS DATA PROGRAMMATICALLY:

JSON-LD is a popular format for linked data which is fully compatible with JSON.

curl -H 'Accept: application/ld+json' 'https://scigraph.springernature.com/pub.10.1038/s41588-018-0183-z'

N-Triples is a line-based linked data format ideal for batch operations.

curl -H 'Accept: application/n-triples' 'https://scigraph.springernature.com/pub.10.1038/s41588-018-0183-z'

Turtle is a human-readable linked data format.

curl -H 'Accept: text/turtle' 'https://scigraph.springernature.com/pub.10.1038/s41588-018-0183-z'

RDF/XML is a standard XML format for linked data.

curl -H 'Accept: application/rdf+xml' 'https://scigraph.springernature.com/pub.10.1038/s41588-018-0183-z'


 

This table displays all metadata directly associated to this object as RDF triples.

316 TRIPLES      21 PREDICATES      105 URIs      84 LITERALS      20 BLANK NODES

Subject Predicate Object
1 sg:pub.10.1038/s41588-018-0183-z schema:about N117830311d63478b81e0257a4a86c002
2 N12fa170582e1422d8e0e25ce612234d3
3 N289c4d27f6714626b7a2cd8a8c96b867
4 N53d0a59e03104f02aea542a77335d893
5 N61722f86fb9f420db7d8aaceb921a7d6
6 N7292af6bcac14bacb4cdc80b97319351
7 N7308ec8ed98b4cceac7d0fa5d109dc62
8 N84f20b4ed3484aa9ae22ba7dd5e6599f
9 N885f4a3ff9e441adb82caf20f22541d9
10 Nad6c6049130a42448430abf2183365e5
11 Nb679c98d42fb4a068d990fff7997b659
12 Nd0a844384ccc4d3da19477d33aaca845
13 Nf3c54aeb8d3c47d2ac51765c81438150
14 anzsrc-for:06
15 anzsrc-for:0604
16 schema:author N9508c58454ca471488164ea5968046cd
17 schema:citation sg:pub.10.1038/nature09764
18 sg:pub.10.1038/nature15393
19 sg:pub.10.1038/nature18642
20 sg:pub.10.1038/nature19057
21 sg:pub.10.1038/nature24284
22 sg:pub.10.1038/ng.2579
23 sg:pub.10.1038/ng.3359
24 sg:pub.10.1038/ng.3396
25 sg:pub.10.1038/ng.3843
26 sg:pub.10.1038/nn.4404
27 sg:pub.10.1038/nrg3118
28 sg:pub.10.1038/s41588-018-0193-x
29 sg:pub.10.1186/s13742-015-0047-8
30 schema:datePublished 2018-08-13
31 schema:datePublishedReg 2018-08-13
32 schema:description A key public health need is to identify individuals at high risk for a given disease to enable enhanced screening or preventive therapies. Because most common diseases have a genetic component, one important approach is to stratify individuals based on inherited DNA variation1. Proposed clinical applications have largely focused on finding carriers of rare monogenic mutations at several-fold increased risk. Although most disease risk is polygenic in nature2–5, it has not yet been possible to use polygenic predictors to identify individuals at risk comparable to monogenic mutations. Here, we develop and validate genome-wide polygenic scores for five common diseases. The approach identifies 8.0, 6.1, 3.5, 3.2, and 1.5% of the population at greater than threefold increased risk for coronary artery disease, atrial fibrillation, type 2 diabetes, inflammatory bowel disease, and breast cancer, respectively. For coronary artery disease, this prevalence is 20-fold higher than the carrier frequency of rare monogenic mutations conferring comparable risk6. We propose that it is time to contemplate the inclusion of polygenic risk prediction in clinical care, and discuss relevant issues.
33 schema:genre article
34 schema:isAccessibleForFree true
35 schema:isPartOf N85eeed8524274a93bdb97b28a97203eb
36 Nb1633b536fdf4eedaacfa87ddf7d696c
37 sg:journal.1103138
38 schema:keywords RISK6
39 applications
40 approach
41 artery disease
42 atrial fibrillation
43 bowel disease
44 breast cancer
45 cancer
46 care
47 carrier frequency
48 carriers
49 clinical application
50 clinical care
51 common disease
52 components
53 coronary artery disease
54 diabetes
55 disease
56 disease risk
57 enhanced screening
58 fibrillation
59 frequency
60 genetic component
61 genome-wide polygenic scores
62 health needs
63 high risk
64 important approach
65 inclusion
66 individuals
67 inflammatory bowel disease
68 issues
69 monogenic mutations
70 most common diseases
71 most disease risk
72 mutations
73 need
74 polygenic predictors
75 polygenic risk prediction
76 polygenic scores
77 population
78 prediction
79 predictors
80 prevalence
81 preventive therapy
82 public health needs
83 rare monogenic mutations
84 relevant issues
85 risk
86 risk prediction
87 scores
88 screening
89 therapy
90 time
91 type 2 diabetes
92 schema:name Genome-wide polygenic scores for common diseases identify individuals with risk equivalent to monogenic mutations
93 schema:pagination 1219-1224
94 schema:productId N88556ac1ebfe4f2e95ccf2ba68b0036a
95 Na15cf08fc3644f24a1d430f977f766b7
96 Nda986b0650294d8d87010b491a33a64c
97 schema:sameAs https://app.dimensions.ai/details/publication/pub.1106070346
98 https://doi.org/10.1038/s41588-018-0183-z
99 schema:sdDatePublished 2022-11-24T21:02
100 schema:sdLicense https://scigraph.springernature.com/explorer/license/
101 schema:sdPublisher Neef85295a5cf460abeedb04b942c49dc
102 schema:url https://doi.org/10.1038/s41588-018-0183-z
103 sgo:license sg:explorer/license/
104 sgo:sdDataset articles
105 rdf:type schema:ScholarlyArticle
106 N117830311d63478b81e0257a4a86c002 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
107 schema:name Male
108 rdf:type schema:DefinedTerm
109 N12fa170582e1422d8e0e25ce612234d3 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
110 schema:name Female
111 rdf:type schema:DefinedTerm
112 N21f71c695bbb4023a094fc9bc7d62fa8 rdf:first sg:person.07454351775.50
113 rdf:rest Nea71d188a5fb4fbb8622a6e67828c77e
114 N289c4d27f6714626b7a2cd8a8c96b867 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
115 schema:name Humans
116 rdf:type schema:DefinedTerm
117 N4781bb16e3684b0a96a665fc2d146572 rdf:first sg:person.01120503505.13
118 rdf:rest Ndb5c4a2273704753b190a588c3a8dcbb
119 N53d0a59e03104f02aea542a77335d893 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
120 schema:name Aged
121 rdf:type schema:DefinedTerm
122 N56966a914d17476bad037c1f2fe1a049 rdf:first sg:person.0767751267.74
123 rdf:rest rdf:nil
124 N61722f86fb9f420db7d8aaceb921a7d6 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
125 schema:name Mutation
126 rdf:type schema:DefinedTerm
127 N6db8fbc467eb45a994774d0e0890cae3 rdf:first sg:person.01270001061.21
128 rdf:rest Nf5b69ed685854eb4a7021b7a7be2468a
129 N6f68d203115b4c499d9eaa43205258aa rdf:first sg:person.01117710630.56
130 rdf:rest Nc81bf4fe444c4b5fb9e31a94ffbab2ca
131 N7292af6bcac14bacb4cdc80b97319351 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
132 schema:name Genome-Wide Association Study
133 rdf:type schema:DefinedTerm
134 N7308ec8ed98b4cceac7d0fa5d109dc62 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
135 schema:name Multifactorial Inheritance
136 rdf:type schema:DefinedTerm
137 N84f20b4ed3484aa9ae22ba7dd5e6599f schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
138 schema:name Risk Factors
139 rdf:type schema:DefinedTerm
140 N85eeed8524274a93bdb97b28a97203eb schema:issueNumber 9
141 rdf:type schema:PublicationIssue
142 N88556ac1ebfe4f2e95ccf2ba68b0036a schema:name dimensions_id
143 schema:value pub.1106070346
144 rdf:type schema:PropertyValue
145 N885f4a3ff9e441adb82caf20f22541d9 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
146 schema:name Adult
147 rdf:type schema:DefinedTerm
148 N9508c58454ca471488164ea5968046cd rdf:first sg:person.07374640413.24
149 rdf:rest Na70e422b933e47968bb1843195f2bf9f
150 Na15cf08fc3644f24a1d430f977f766b7 schema:name doi
151 schema:value 10.1038/s41588-018-0183-z
152 rdf:type schema:PropertyValue
153 Na70e422b933e47968bb1843195f2bf9f rdf:first sg:person.014110301753.77
154 rdf:rest N6f68d203115b4c499d9eaa43205258aa
155 Nad6c6049130a42448430abf2183365e5 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
156 schema:name Disease
157 rdf:type schema:DefinedTerm
158 Nb1633b536fdf4eedaacfa87ddf7d696c schema:volumeNumber 50
159 rdf:type schema:PublicationVolume
160 Nb679c98d42fb4a068d990fff7997b659 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
161 schema:name Middle Aged
162 rdf:type schema:DefinedTerm
163 Nc81bf4fe444c4b5fb9e31a94ffbab2ca rdf:first sg:person.0653567411.03
164 rdf:rest N21f71c695bbb4023a094fc9bc7d62fa8
165 Nd0a844384ccc4d3da19477d33aaca845 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
166 schema:name Genetic Predisposition to Disease
167 rdf:type schema:DefinedTerm
168 Nda986b0650294d8d87010b491a33a64c schema:name pubmed_id
169 schema:value 30104762
170 rdf:type schema:PropertyValue
171 Ndb5c4a2273704753b190a588c3a8dcbb rdf:first sg:person.01260666165.62
172 rdf:rest N6db8fbc467eb45a994774d0e0890cae3
173 Nea71d188a5fb4fbb8622a6e67828c77e rdf:first sg:person.0773123264.12
174 rdf:rest N4781bb16e3684b0a96a665fc2d146572
175 Neef85295a5cf460abeedb04b942c49dc schema:name Springer Nature - SN SciGraph project
176 rdf:type schema:Organization
177 Nf3c54aeb8d3c47d2ac51765c81438150 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
178 schema:name Polymorphism, Single Nucleotide
179 rdf:type schema:DefinedTerm
180 Nf5b69ed685854eb4a7021b7a7be2468a rdf:first sg:person.01300106701.65
181 rdf:rest N56966a914d17476bad037c1f2fe1a049
182 anzsrc-for:06 schema:inDefinedTermSet anzsrc-for:
183 schema:name Biological Sciences
184 rdf:type schema:DefinedTerm
185 anzsrc-for:0604 schema:inDefinedTermSet anzsrc-for:
186 schema:name Genetics
187 rdf:type schema:DefinedTerm
188 sg:grant.2419858 http://pending.schema.org/fundedItem sg:pub.10.1038/s41588-018-0183-z
189 rdf:type schema:MonetaryGrant
190 sg:grant.2421237 http://pending.schema.org/fundedItem sg:pub.10.1038/s41588-018-0183-z
191 rdf:type schema:MonetaryGrant
192 sg:grant.2423351 http://pending.schema.org/fundedItem sg:pub.10.1038/s41588-018-0183-z
193 rdf:type schema:MonetaryGrant
194 sg:grant.2542084 http://pending.schema.org/fundedItem sg:pub.10.1038/s41588-018-0183-z
195 rdf:type schema:MonetaryGrant
196 sg:grant.2684605 http://pending.schema.org/fundedItem sg:pub.10.1038/s41588-018-0183-z
197 rdf:type schema:MonetaryGrant
198 sg:grant.3537179 http://pending.schema.org/fundedItem sg:pub.10.1038/s41588-018-0183-z
199 rdf:type schema:MonetaryGrant
200 sg:grant.3933199 http://pending.schema.org/fundedItem sg:pub.10.1038/s41588-018-0183-z
201 rdf:type schema:MonetaryGrant
202 sg:grant.4242960 http://pending.schema.org/fundedItem sg:pub.10.1038/s41588-018-0183-z
203 rdf:type schema:MonetaryGrant
204 sg:grant.4730138 http://pending.schema.org/fundedItem sg:pub.10.1038/s41588-018-0183-z
205 rdf:type schema:MonetaryGrant
206 sg:grant.7171348 http://pending.schema.org/fundedItem sg:pub.10.1038/s41588-018-0183-z
207 rdf:type schema:MonetaryGrant
208 sg:grant.7211970 http://pending.schema.org/fundedItem sg:pub.10.1038/s41588-018-0183-z
209 rdf:type schema:MonetaryGrant
210 sg:grant.8472499 http://pending.schema.org/fundedItem sg:pub.10.1038/s41588-018-0183-z
211 rdf:type schema:MonetaryGrant
212 sg:journal.1103138 schema:issn 1061-4036
213 1546-1718
214 schema:name Nature Genetics
215 schema:publisher Springer Nature
216 rdf:type schema:Periodical
217 sg:person.01117710630.56 schema:affiliation grid-institutes:grid.66859.34
218 schema:familyName Aragam
219 schema:givenName Krishna G.
220 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01117710630.56
221 rdf:type schema:Person
222 sg:person.01120503505.13 schema:affiliation grid-institutes:grid.66859.34
223 schema:familyName Natarajan
224 schema:givenName Pradeep
225 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01120503505.13
226 rdf:type schema:Person
227 sg:person.01260666165.62 schema:affiliation grid-institutes:grid.66859.34
228 schema:familyName Lander
229 schema:givenName Eric S.
230 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01260666165.62
231 rdf:type schema:Person
232 sg:person.01270001061.21 schema:affiliation grid-institutes:grid.66859.34
233 schema:familyName Lubitz
234 schema:givenName Steven A.
235 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01270001061.21
236 rdf:type schema:Person
237 sg:person.01300106701.65 schema:affiliation grid-institutes:grid.66859.34
238 schema:familyName Ellinor
239 schema:givenName Patrick T.
240 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01300106701.65
241 rdf:type schema:Person
242 sg:person.014110301753.77 schema:affiliation grid-institutes:grid.66859.34
243 schema:familyName Chaffin
244 schema:givenName Mark
245 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.014110301753.77
246 rdf:type schema:Person
247 sg:person.0653567411.03 schema:affiliation grid-institutes:grid.66859.34
248 schema:familyName Haas
249 schema:givenName Mary E.
250 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0653567411.03
251 rdf:type schema:Person
252 sg:person.07374640413.24 schema:affiliation grid-institutes:grid.66859.34
253 schema:familyName Khera
254 schema:givenName Amit V.
255 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.07374640413.24
256 rdf:type schema:Person
257 sg:person.07454351775.50 schema:affiliation grid-institutes:grid.66859.34
258 schema:familyName Roselli
259 schema:givenName Carolina
260 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.07454351775.50
261 rdf:type schema:Person
262 sg:person.0767751267.74 schema:affiliation grid-institutes:grid.66859.34
263 schema:familyName Kathiresan
264 schema:givenName Sekar
265 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0767751267.74
266 rdf:type schema:Person
267 sg:person.0773123264.12 schema:affiliation grid-institutes:grid.66859.34
268 schema:familyName Choi
269 schema:givenName Seung Hoan
270 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0773123264.12
271 rdf:type schema:Person
272 sg:pub.10.1038/nature09764 schema:sameAs https://app.dimensions.ai/details/publication/pub.1037658930
273 https://doi.org/10.1038/nature09764
274 rdf:type schema:CreativeWork
275 sg:pub.10.1038/nature15393 schema:sameAs https://app.dimensions.ai/details/publication/pub.1021812064
276 https://doi.org/10.1038/nature15393
277 rdf:type schema:CreativeWork
278 sg:pub.10.1038/nature18642 schema:sameAs https://app.dimensions.ai/details/publication/pub.1036558635
279 https://doi.org/10.1038/nature18642
280 rdf:type schema:CreativeWork
281 sg:pub.10.1038/nature19057 schema:sameAs https://app.dimensions.ai/details/publication/pub.1022281897
282 https://doi.org/10.1038/nature19057
283 rdf:type schema:CreativeWork
284 sg:pub.10.1038/nature24284 schema:sameAs https://app.dimensions.ai/details/publication/pub.1092349555
285 https://doi.org/10.1038/nature24284
286 rdf:type schema:CreativeWork
287 sg:pub.10.1038/ng.2579 schema:sameAs https://app.dimensions.ai/details/publication/pub.1020935195
288 https://doi.org/10.1038/ng.2579
289 rdf:type schema:CreativeWork
290 sg:pub.10.1038/ng.3359 schema:sameAs https://app.dimensions.ai/details/publication/pub.1019843926
291 https://doi.org/10.1038/ng.3359
292 rdf:type schema:CreativeWork
293 sg:pub.10.1038/ng.3396 schema:sameAs https://app.dimensions.ai/details/publication/pub.1034378235
294 https://doi.org/10.1038/ng.3396
295 rdf:type schema:CreativeWork
296 sg:pub.10.1038/ng.3843 schema:sameAs https://app.dimensions.ai/details/publication/pub.1084863147
297 https://doi.org/10.1038/ng.3843
298 rdf:type schema:CreativeWork
299 sg:pub.10.1038/nn.4404 schema:sameAs https://app.dimensions.ai/details/publication/pub.1018996868
300 https://doi.org/10.1038/nn.4404
301 rdf:type schema:CreativeWork
302 sg:pub.10.1038/nrg3118 schema:sameAs https://app.dimensions.ai/details/publication/pub.1001779725
303 https://doi.org/10.1038/nrg3118
304 rdf:type schema:CreativeWork
305 sg:pub.10.1038/s41588-018-0193-x schema:sameAs https://app.dimensions.ai/details/publication/pub.1106026183
306 https://doi.org/10.1038/s41588-018-0193-x
307 rdf:type schema:CreativeWork
308 sg:pub.10.1186/s13742-015-0047-8 schema:sameAs https://app.dimensions.ai/details/publication/pub.1037894462
309 https://doi.org/10.1186/s13742-015-0047-8
310 rdf:type schema:CreativeWork
311 grid-institutes:grid.66859.34 schema:alternateName Cardiovascular Disease Initiative of the Broad Institute of Harvard and MIT, Cambridge, MA, USA
312 schema:name Cardiology Division of the Department of Medicine, Massachusetts General Hospital, Boston, MA, USA
313 Cardiovascular Disease Initiative of the Broad Institute of Harvard and MIT, Cambridge, MA, USA
314 Center for Genomic Medicine, Massachusetts General Hospital, Boston, MA, USA
315 Harvard Medical School, Boston, MA, USA
316 rdf:type schema:Organization
 




Preview window. Press ESC to close (or click here)


...