PGS Publication: PGP000204

Publication Information (EuropePMC)
Title Immunotherapy-mediated thyroid dysfunction: genetic risk and impact on outcomes with PD-1 blockade in non-small cell lung cancer.
PubMed ID 34244291(Europe PMC)
doi 10.1158/1078-0432.ccr-21-0921
Publication Date July 8, 2021
Journal Clin Cancer Res
Author(s) Luo J, Martucci VL, Quandt Z, Groha S, Murray MH, Lovly CM, Rizvi H, Egger JV, Plodkowski AJ, Abu-Akeel M, Schulze I, Merghoub T, Cardenas E, Huntsman S, Li M, Hu D, Gubens MA, Gusev A, Aldrich MC, Hellmann MD, Ziv E.
Released in PGS Catalog: July 29, 2021

Associated Polygenic Score(s)

Filter PGS by Participant Ancestry
Individuals included in:
G - Source of Variant Associations (GWAS)
D - Score Development/Training
E - PGS Evaluation
List of ancestries includes:
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Multi-ancestry (including European)
Multi-ancestry (excluding European)
African
East Asian
South Asian
Additional Asian Ancestries
European
Greater Middle Eastern
Hispanic or Latin American
Additional Diverse Ancestries
Not Reported

PGS Developed By This Publication

Polygenic Score ID & Name PGS Publication ID (PGP) Reported Trait Mapped Trait(s) (Ontology) Number of Variants Ancestry distribution Scoring File (FTP Link)
PGS000821
(PRS_hypomed)
PGP000204 |
Luo J et al. Clin Cancer Res (2021)
Thyroid medication use Thyroid preparation use measurement 872,391
-
https://ftp.ebi.ac.uk/pub/databases/spot/pgs/scores/PGS000821/ScoringFiles/PGS000821.txt.gz
PGS000820
(PRS_hypothyroidism)
PGP000204 |
Luo J et al. Clin Cancer Res (2021)
Hypothyroidism (self-reported) hypothyroidism 890,908
-
https://ftp.ebi.ac.uk/pub/databases/spot/pgs/scores/PGS000820/ScoringFiles/PGS000820.txt.gz

Performance Metrics

Disclaimer: The performance metrics are displayed as reported by the source studies. It is important to note that metrics are not necessarily comparable with each other. For example, metrics depend on the sample characteristics (described by the PGS Catalog Sample Set [PSS] ID), phenotyping, and statistical modelling. Please refer to the source publication for additional guidance on performance.

PGS Performance
Metric ID (PPM)
Evaluated Score PGS Sample Set ID
(PSS)
Performance Source Trait PGS Effect Sizes
(per SD change)
Classification Metrics Other Metrics Covariates Included in the Model PGS Performance:
Other Relevant Information
PPM002193 PGS000820
(PRS_hypothyroidism)
PSS001068|
European Ancestry|
51,070 individuals
PGP000204 |
Luo J et al. Clin Cancer Res (2021)
Reported Trait: Spontaneous hypothyroidism OR: 1.33 [1.29, 1.37] AUROC: 0.6 Age, sex, PCs(1-10)
PPM002194 PGS000821
(PRS_hypomed)
PSS001068|
European Ancestry|
51,070 individuals
PGP000204 |
Luo J et al. Clin Cancer Res (2021)
Reported Trait: Spontaneous hypothyroidism AUROC: 0.6 Age, sex, PCs(1-10)
PPM002195 PGS000820
(PRS_hypothyroidism)
PSS001070|
Multi-ancestry (including European)|
744 individuals
PGP000204 |
Luo J et al. Clin Cancer Res (2021)
Reported Trait: Immune checkpoint inhibitor therapy induced immune-related thyroid dysfunction in individuals with non-small cell lung cancer HR: 1.34 [1.08, 1.66] AUROC: 0.6 Age, sex, PCs(1-10)
PPM002197 PGS000820
(PRS_hypothyroidism)
PSS001070|
Multi-ancestry (including European)|
744 individuals
PGP000204 |
Luo J et al. Clin Cancer Res (2021)
Reported Trait: Anti-PD-(L)1 monotherapy induced immune-related thyroid dysfunction in individuals with non-small cell lung cancer HR: 1.34 [1.07, 1.69] Age, sex, PCs(1-10)
PPM002199 PGS000820
(PRS_hypothyroidism)
PSS001069|
Multi-ancestry (including European)|
561 individuals
PGP000204 |
Luo J et al. Clin Cancer Res (2021)
Reported Trait: Immune checkpoint inhibitor therapy induced immune-related thyroid dysfunction in individuals with non-small cell lung cancer HR: 1.39 [1.07, 1.82] AUROC: 0.64 Age, sex, PCs(1-10)
PPM002198 PGS000820
(PRS_hypothyroidism)
PSS001071|
European Ancestry|
634 individuals
PGP000204 |
Luo J et al. Clin Cancer Res (2021)
Reported Trait: Immune checkpoint inhibitor therapy induced immune-related thyroid dysfunction in individuals with non-small cell lung cancer HR: 1.27 [1.02, 1.59] Age, sex
PPM002196 PGS000821
(PRS_hypomed)
PSS001070|
Multi-ancestry (including European)|
744 individuals
PGP000204 |
Luo J et al. Clin Cancer Res (2021)
Reported Trait: Immune checkpoint inhibitor therapy induced immune-related thyroid dysfunction in individuals with non-small cell lung cancer HR: 1.32 [1.07, 1.63] Age, sex, PCs(1-10)
PPM002200 PGS000821
(PRS_hypomed)
PSS001070|
Multi-ancestry (including European)|
744 individuals
PGP000204 |
Luo J et al. Clin Cancer Res (2021)
Reported Trait: Immune checkpoint inhibitor therapy induced immune-related thyroid dysfunction in individuals with non-small cell lung cancer AUROC: 0.7 Age, sex, PCs(1-10)

Evaluated Samples

PGS Sample Set ID
(PSS)
Phenotype Definitions and Methods Participant Follow-up Time Sample Numbers Age of Study Participants Sample Ancestry Additional Ancestry Description Cohort(s) Additional Sample/Cohort Information
PSS001068 Spontaneous hypothyroidism cases and controls were defined using phecodes, which aggregate similar ICD-9-CM and ICD-10-CM. Individuals must have had at least 2 ICD codes for hypothyroidism to be assigned a phecode, and individuals with other thyroid diseases were excluded from the control set. 51,070 individuals European BioVu
PSS001069 All individuals had non-small cell lung cancer (NSCLC) and were receiving immune checkpoint inhibitor (CPI) therapy. Cases were individuals who had experienced immune-related thyroid dysfunction following CPI therapy. A thyroid event after the start of CPI therapy was defined as either (1) incident hypothyroidism or (2) transient incident hyperthyroidism followed by incident hypothyroidism. Incident hypothyroidism was defined as (a) a TSH of ≥ 10 mU/L or (b) TSH of ≥ 5 mU/L with a new prescription of levothyroxine ≥ 50 mcg. Incident hyperthyroidism was defined as TSH < 0.05 mU/L. Median = 12.0 months
[
  • 42 cases
  • , 519 controls
]
,
44.0 % Male samples
Median = 67.0 years
Iqr = [60.0, 74.0] years
European, African unspecified, Asian unspecified, Hispanic or Latin American, NR European = 506, African unspecified = 22, Asian unspecified = 17, Not reported = 6, Hispanic or Latin American = 10 Cases and controls were obtained from the Dana-Farber Cancer Institute (DFCI)
PSS001070 All individuals had non-small cell lung cancer (NSCLC) and were receiving immune checkpoint inhibitor (CPI) therapy. of the 744 individuals receiving CPI therapy, 659 were being treated with Anti-PD-(L)1 monotherapy whilst 85 were being treated with Anti-PD-(L)1+CTLA-4 combination therapy. Cases were individuals who had experienced immune-related thyroid dysfunction following CPI therapy. A thyroid event after the start of CPI therapy was defined as either (1) incident hypothyroidism or (2) transient incident hyperthyroidism followed by incident hypothyroidism. Incident hypothyroidism was defined as (a) a TSH of ≥ 10 mU/L or (b) TSH of ≥ 5 mU/L with a new prescription of levothyroxine ≥ 50 mcg. Incident hyperthyroidism was defined as TSH < 0.05 mU/L.
[
  • 95 cases
  • , 649 controls
]
,
50.94 % Male samples
European, African unspecified, Asian unspecified, Hispanic or Latin American, NR European = 634, African unspecified = 50, Asian unspecified = 36, Not reported = 4, Hispanic or Latin American = 20 MSKCC Additional cases and controls were obtained from the Vanderbilt University Medical Centre (VUMC)
PSS001071 All individuals had non-small cell lung cancer (NSCLC) and were receiving immune checkpoint inhibitor (CPI) therapy. Cases were individuals who had experienced immune-related thyroid dysfunction following CPI therapy. A thyroid event after the start of CPI therapy was defined as either (1) incident hypothyroidism or (2) transient incident hyperthyroidism followed by incident hypothyroidism. Incident hypothyroidism was defined as (a) a TSH of ≥ 10 mU/L or (b) TSH of ≥ 5 mU/L with a new prescription of levothyroxine ≥ 50 mcg. Incident hyperthyroidism was defined as TSH < 0.05 mU/L. 634 individuals European MSKCC Additional cases and controls were obtained from the Vanderbilt University Medical Centre (VUMC)