TY - JOUR
T1 - Identification of sex-specific genetic associations in response to opioid analgesics in a White, non-Hispanic cohort from Southeast Minnesota
AU - Lopes, Guilherme S.
AU - Lopes, Jaime L.
AU - Bielinski, Suzette J.
AU - Armasu, Sebastian M.
AU - Zhu, Ye
AU - Cavanaugh, Dana C.
AU - Moyer, Ann M.
AU - Jacobson, Debra J.
AU - Wang, Liwei
AU - Jiang, Ruoxiang
AU - St. Sauver, Jennifer L.
AU - Larson, Nicholas B.
N1 - Funding Information:
This work was supported by the Mayo Clinic Specialized Center of Research Excellent on Sex Differences, the Mayo Clinic Center for Individualized Medicine, the Robert D. and Patricia E. Kern Center for the Science of Health Care Delivery, and the National Institutes of Health grants [U19 GM61388 (The Pharmacogenomics Research Network), R01 GM28157, U01 HG005137, R01 GM125633, R01 AG034676 (The Rochester Epidemiology Project), U54 AG044170 (Sex-Specific Effects of Endocrine Disruption on Aging and Alzheimer’s Disease)], and [U01 HG06379 and U01 HG06379 Supplement (The Electronic Medical Record and Genomics (eMERGE) Network)].
Publisher Copyright:
© 2022, The Author(s).
PY - 2022/3
Y1 - 2022/3
N2 - The study of sex-specific genetic associations with opioid response may improve the understanding of inter-individual variability in pain treatments. We investigated sex-specific associations between genetic variation and opioid response. We identified participants in the RIGHT Study prescribed codeine, tramadol, hydrocodone, and oxycodone between 01/01/2005 and 12/31/2017. Prescriptions were collapsed into codeine/tramadol and hydrocodone/oxycodone. Outcomes included poor pain control and adverse reactions within six weeks after prescription date. We performed gene-level and single-variant association analyses stratified by sex. We included 7169 non-Hispanic white participants and a total of 1940 common and low-frequency variants (MAF > 0.01). Common variants in MACROD2 (rs76026520), CYP1B1 (rs1056837, rs1056836), and CYP2D6 (rs35742686) were associated with outcomes. At the gene level, FAAH, SCN1A, and TYMS had associations for men and women, and NAT2, CYP3A4, CYP1A2, and SLC22A2 had associations for men only. Our findings highlight the importance of considering sex in association studies on opioid response.
AB - The study of sex-specific genetic associations with opioid response may improve the understanding of inter-individual variability in pain treatments. We investigated sex-specific associations between genetic variation and opioid response. We identified participants in the RIGHT Study prescribed codeine, tramadol, hydrocodone, and oxycodone between 01/01/2005 and 12/31/2017. Prescriptions were collapsed into codeine/tramadol and hydrocodone/oxycodone. Outcomes included poor pain control and adverse reactions within six weeks after prescription date. We performed gene-level and single-variant association analyses stratified by sex. We included 7169 non-Hispanic white participants and a total of 1940 common and low-frequency variants (MAF > 0.01). Common variants in MACROD2 (rs76026520), CYP1B1 (rs1056837, rs1056836), and CYP2D6 (rs35742686) were associated with outcomes. At the gene level, FAAH, SCN1A, and TYMS had associations for men and women, and NAT2, CYP3A4, CYP1A2, and SLC22A2 had associations for men only. Our findings highlight the importance of considering sex in association studies on opioid response.
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U2 - 10.1038/s41397-022-00265-9
DO - 10.1038/s41397-022-00265-9
M3 - Article
C2 - 35102242
AN - SCOPUS:85123952582
VL - 22
SP - 117
EP - 123
JO - Pharmacogenomics Journal
JF - Pharmacogenomics Journal
SN - 1470-269X
IS - 2
ER -