Protocol detail

PRS Validation for Hypothyroidism Risk

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External validation of the PRS was performed in a population of 51,070 individuals of European descent with no cancer diagnosis in BioVU. European ancestry was determined using principal components analysis (PCA). Individuals in this cohort were genotyped on the Illumina Expanded Multi-Ethnic Genotyping Array and subjected to standard quality control. Imputation was performed with the Haplotype Reference Consortium reference panel on the Michigan Imputation Server(36 (link)). PRS were calculated using the previously derived weights from LDpred and the score function in PLINK 1.9(37 (link),38 (link)). Spontaneous hypothyroidism cases and controls were defined using phecodes, which aggregate similar ICD-9-CM and ICD-10-CM. Individuals must have at least 2 ICD codes for hypothyroidism to be assigned a phecode, and individuals with other thyroid diseases were excluded from the control set.

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Luo J., Martucci V.L., Quandt Z., Groha S., Murray M.H., Lovly C.M., Rizvi H., Egger J.V., Plodkowski A.J., Abu-Akeel M., Schulze I., Merghoub T., Cardenas E., Huntsman S., Li M., Hu D., Gubens M.A., Gusev A., Aldrich M.C., Hellmann M.D, & Ziv E. (2021). Immunotherapy-mediated thyroid dysfunction: genetic risk and impact on outcomes with PD-1 blockade in non-small cell lung cancer. Clinical cancer research : an official journal of the American Association for Cancer Research, 27(18), 5131-5140.

Publication 2021

Expanded Multi-Ethnic Genotyping Array

Cancer Diagnosis European Haplotype Hypothyroidism Thyroid diseases

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Variable analysis

independent variables

Polygenic risk score (PRS)

dependent variables

Spontaneous hypothyroidism

control variables

European ancestry determined using principal components analysis (PCA)
Individuals genotyped on the Illumina Expanded Multi-Ethnic Genotyping Array and subjected to standard quality control
Imputation performed with the Haplotype Reference Consortium reference panel on the Michigan Imputation Server
Individuals with other thyroid diseases were excluded from the control set

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