| 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. |
| Polygenic Score ID & Name | PGS Publication ID (PGP) | Reported Trait | Mapped Trait(s) (Ontology) | Number of Variants |
Ancestry distribution GWAS Dev Eval |
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 |
|
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) | — |
| 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) | — |
| 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) | — |
|
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 | [ ,
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 | NR | 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. | — | [ ,
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) |