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Rask-Andersen, M., Ivansson, E., Höglund, J., Ek, W. E., Karlsson, T. & Johansson, Å. (2023). Adiposity and sex-specific cancer risk.. Cancer Cell, 41(6), 1186-1197.e4
Åpne denne publikasjonen i ny fane eller vindu >>Adiposity and sex-specific cancer risk.
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2023 (engelsk)Inngår i: Cancer Cell, ISSN 1535-6108, E-ISSN 1878-3686, Vol. 41, nr 6, s. 1186-1197.e4Artikkel i tidsskrift (Fagfellevurdert) Published
Abstract [en]

Obesity is associated with several types of cancer and fat distribution, which differs dramatically between sexes, has been suggested to be an independent risk factor. However, sex-specific effects on cancer risk have rarely been studied. Here we estimate the effects of fat accumulation and distribution on cancer risk in females and males. We performed a prospective study in 442,519 UK Biobank participants, for 19 cancer types and additional histological subtypes, with a mean follow-up time of 13.4 years. Cox proportional hazard models were used to estimate the effect of 14 different adiposity phenotypes on cancer rates, and a 5% false discovery rate was considered statistically significant. Adiposity-related traits are associated with all but three cancer types, and fat accumulation is associated with a larger number of cancers compared to fat distribution. In addition, fat accumulation or distribution exhibit differential effects between sexes on colorectal, esophageal, and liver cancer.

Emneord
BMI, UK Biobank, WHRadjBMI, body fat distribution, cancer, cox proportional hazard modeling, obesity, risk factors, sex-interactions
HSV kategori
Identifikatorer
urn:nbn:se:uu:diva-505445 (URN)10.1016/j.ccell.2023.05.010 (DOI)001024362800001 ()37311415 (PubMedID)
Forskningsfinansiär
Swedish Research Council, 2018-05973Swedish Cancer Society, 19 0383 PjSwedish Cancer Society, 21 0447 FESwedish Cancer Society, 22 2222 PjSwedish Research Council, 2019-01497Sjöberg Foundation
Tilgjengelig fra: 2023-06-20 Laget: 2023-06-20 Sist oppdatert: 2023-08-08bibliografisk kontrollert
Karlsson, T., Hadizadeh, F., Rask-Andersen, M., Johansson, Å. & Ek, W. E. (2023). Body Mass Index and the Risk of Rheumatic Disease: Linear and Nonlinear Mendelian Randomization Analyses. Arthritis & Rheumatology, 75(11), 2027-2035
Åpne denne publikasjonen i ny fane eller vindu >>Body Mass Index and the Risk of Rheumatic Disease: Linear and Nonlinear Mendelian Randomization Analyses
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2023 (engelsk)Inngår i: Arthritis & Rheumatology, ISSN 2326-5191, E-ISSN 2326-5205, Vol. 75, nr 11, s. 2027-2035Artikkel i tidsskrift (Fagfellevurdert) Published
Abstract [en]

OBJECTIVE: While the association between obesity and risk of rheumatic disease is well established, the precise causal relation has not been conclusively proved. Here, we estimate the causal effect of body mass index (BMI) on the risk of developing five different rheumatic diseases.

METHODS: Linear and nonlinear mendelian randomization (MR) were used to estimate the effect of BMI on risk of rheumatic disease, and sex-specific effects were identified. Analyses were performed in 361,952 participants from the UK Biobank cohort for the five rheumatic diseases: rheumatoid arthritis (N=8,381 cases), osteoarthritis (N=87,430), psoriatic arthropathy (N=933), gout (N=13,638), and inflammatory spondylitis (N=4,328).

RESULTS: Using linear MR, we found that one standard deviation higher BMI increases the incidence rate for rheumatoid arthritis (IRR=1.52; 95% CI=1.36-1.69), osteoarthritis (IRR=1.49; 1.43-1.55), psoriatic arthropathy (IRR=1.80; 1.31-2.48), gout (IRR=1.73; 1.56-1.92), and inflammatory spondylitis (IRR=1.34; 1.14-1.57) in all individuals. BMI was found to be a stronger risk factor in women compared to men for psoriatic arthropathy (sex-interaction P=3.3×10-4 ) and gout (P=4.3×10-3 ), and the effect on osteoarthritis was stronger in premenopausal compared to postmenopausal women (P=1.8×10-3 ). Nonlinear effects of BMI were identified for osteoarthritis and gout in men, and for gout in women. The nonlinearity for gout was also more extreme in men compared to women (P=0.03).

CONCLUSION: Higher BMI causes an increased risk for rheumatic disease, an effect that is more pronounced in women for both gout and psoriatic arthropathy. The novel sex- and BMI-specific causal effects identified here, give further insight into rheumatic-disease etiology and mark an important step towards personalized medicine.

sted, utgiver, år, opplag, sider
John Wiley & Sons, 2023
HSV kategori
Identifikatorer
urn:nbn:se:uu:diva-505446 (URN)10.1002/art.42613 (DOI)001072629700001 ()37219954 (PubMedID)
Forskningsfinansiär
Swedish Research Council, 2018-05973Swedish National Infrastructure for Computing (SNIC), sens2017538
Tilgjengelig fra: 2023-06-20 Laget: 2023-06-20 Sist oppdatert: 2024-02-26bibliografisk kontrollert
Johansson, T., Vinther Larsen, S., Bui, M., Ek, W. E., Karlsson, T. & Johansson, Å. (2023). Population-based cohort study of oral contraceptive use and risk of depression. Epidemiology and Psychiatric Sciences, 32, Article ID e39.
Åpne denne publikasjonen i ny fane eller vindu >>Population-based cohort study of oral contraceptive use and risk of depression
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2023 (engelsk)Inngår i: Epidemiology and Psychiatric Sciences, ISSN 2045-7960, E-ISSN 2045-7979, Vol. 32, artikkel-id e39Artikkel i tidsskrift (Fagfellevurdert) Published
Abstract [en]

AIM: Research on the effect of oral contraceptive (OC) use on the risk of depression shows inconsistent findings, especially in adult OC users. One possible reason for this inconsistency is the omission of women who discontinue OCs due to adverse mood effects, leading to healthy user bias. To address this issue, we aim to estimate the risk of depression that is associated with the initiation of OCs as well as the effect of OC use on lifetime risk of depression.

METHODS: This is a population-based cohort study based on data from 264,557 women from the UK Biobank. Incidence of depression was addressed via interviews, inpatient hospital or primary care data. The hazard ratio (HR) between OC use and incident depression was estimated by multivariable Cox regression with OC use as a time-varying exposure. To validate causality, we examined familial confounding in 7,354 sibling pairs.

RESULTS: We observed that the first 2 years of OC use were associated with a higher rate of depression compared to never users (HR = 1.71, 95% confidence interval [CI]: 1.55-1.88). Although the risk was not as pronounced beyond the first 2 years, ever OC use was still associated with an increased lifetime risk of depression (HR = 1.05, 95% CI: 1.01-1.09). Previous OC use were associated with a higher rate of depression compared to never users, with adolescent OC users driving the increased hazard (HR = 1.18, 95% CI: 1.12-1.25). No significant association were observed among adult OC users who had previously used OCs (HR = 1.00, 95% CI: 0.95-1.04). Notably, the sibling analysis provided further evidence for a causal effect of OC use on the risk of depression.

CONCLUSIONS: Our findings suggest that the use of OCs, particularly during the first 2 years, increases the risk of depression. Additionally, OC use during adolescence might increase the risk of depression later in life. Our results are consistent with a causal relationship between OC use and depression, as supported by the sibling analysis. This study highlights the importance of considering the healthy user bias as well as family-level confounding in studies of OC use and mental health outcomes. Physicians and patients should be aware of this potential risk when considering OCs, and individualized risk-benefit assessments should be conducted.

sted, utgiver, år, opplag, sider
Cambridge University Press, 2023
Emneord
depression, epidemiology, mental health, women
HSV kategori
Identifikatorer
urn:nbn:se:uu:diva-505448 (URN)10.1017/S2045796023000525 (DOI)001004326300001 ()37303201 (PubMedID)
Forskningsfinansiär
Swedish Research CouncilThe Swedish Brain FoundationUppsala University
Tilgjengelig fra: 2023-06-20 Laget: 2023-06-20 Sist oppdatert: 2023-10-05bibliografisk kontrollert
Kierczak, M., Rafati, N., Höglund, J., Gourlé, H., Lo Faro, V., Schmitz, D., . . . Johansson, Å. (2022). Contribution of rare whole-genome sequencing variants to plasma protein levels and the missing heritability. Nature Communications, 13, Article ID 2532.
Åpne denne publikasjonen i ny fane eller vindu >>Contribution of rare whole-genome sequencing variants to plasma protein levels and the missing heritability
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2022 (engelsk)Inngår i: Nature Communications, E-ISSN 2041-1723, Vol. 13, artikkel-id 2532Artikkel i tidsskrift (Fagfellevurdert) Published
Abstract [en]

Despite the success of genome-wide association studies, much of the genetic contribution to complex traits remains unexplained. Here, we analysed high coverage whole genome sequencing data, to evaluate the contribution of rare genetic variants to 414 plasma proteins. The frequency distribution of genetic variants was skewed towards the rare spectrum, and damaging variants were more often rare. We estimated that less than 4.3% of the narrow-sense heritability is expected to be explained by rare variants in our cohort. Using a gene-based approach, we identified Cis-associations for 237 of the proteins, which is slightly more compared to a GWAS (N=213), and we identified 34 loci in Trans. Several associations were driven by rare variants, and rare variants had on average larger phenotypic effects. We conclude therefore that rare variants could be of  importance for precision medicine applications, but have a more limited contribution to the missing heritability of complex diseases.

sted, utgiver, år, opplag, sider
Springer Nature, 2022
Emneord
Rare variants, SKAT, Protein Biomarkers, Hidden heritability, Missing heritability, GWAS
HSV kategori
Identifikatorer
urn:nbn:se:uu:diva-470178 (URN)10.1038/s41467-022-30208-8 (DOI)000792848500027 ()35534486 (PubMedID)
Forskningsfinansiär
Swedish Research Council, 2019-01497Swedish Heart Lung Foundation, 20200687Knut and Alice Wallenberg FoundationScience for Life Laboratory, SciLifeLabSwedish National Infrastructure for Computing (SNIC), SNIC 2018/8-372Swedish Research Council, 2018-05973
Merknad

Titel in Thesis: The contribution of rare whole genome sequencing variants to plasma protein levels and to the missing heritability

De fem första författarna delar förstaförfattarskapet

Tilgjengelig fra: 2022-03-21 Laget: 2022-03-21 Sist oppdatert: 2023-03-28bibliografisk kontrollert
Höglund, J., Hadizadeh, F., Ek, W. E., Karlsson, T. & Johansson, Å. (2022). Gene-based variant analysis of whole-exome sequencing in relation to eosinophil count. Frontiers in Immunology, 13, Article ID 862255.
Åpne denne publikasjonen i ny fane eller vindu >>Gene-based variant analysis of whole-exome sequencing in relation to eosinophil count
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2022 (engelsk)Inngår i: Frontiers in Immunology, E-ISSN 1664-3224, Vol. 13, artikkel-id 862255Artikkel i tidsskrift (Fagfellevurdert) Published
Abstract [en]

Eosinophils play important roles in the release of cytokine mediators in response to inflammation. Many associations between common genetic variants and eosinophils have already been reported, using single nucleotide polymorphism (SNP) array data. Here, we have analyzed 200,000 whole-exome sequences (WES) from the UK Biobank cohort and performed gene-based analyses of eosinophil count. We defined five different variant weighting schemes to incorporate information on both deleteriousness and frequency. A total of 220 genes in 55 distinct (>10 Mb apart) genomic regions were found to be associated with eosinophil count, of which seven genes (ALOX15, CSF2RB, IL17RA, IL33, JAK2, S1PR4, and SH2B3) are driven by rare variants, independent of common variants identified in genome-wide association studies. Two additional genes, NPAT and RMI1, have not been associated with eosinophil count before and are considered novel eosinophil loci. These results increase our knowledge about the effect of rare variants on eosinophil count, which can be of great value for further identification of therapeutic targets.

sted, utgiver, år, opplag, sider
Frontiers Media S.A., 2022
Emneord
exome sequencing, eosinophils, association testing, inflammation, UK Biobank
HSV kategori
Forskningsprogram
Medicinsk genetik
Identifikatorer
urn:nbn:se:uu:diva-470143 (URN)10.3389/fimmu.2022.862255 (DOI)001026370700001 ()35935937 (PubMedID)
Forskningsfinansiär
Swedish Research Council, 2019-01497Swedish Heart Lung Foundation, 20200687Åke Wiberg FoundationM Borgströms stiftelse för ärftlighetsforskningAgnes and Mac Rudberg Foundation
Tilgjengelig fra: 2022-03-21 Laget: 2022-03-21 Sist oppdatert: 2024-01-17bibliografisk kontrollert
Johansson, Å., Schmitz, D., Höglund, J., Hadizadeh, F., Karlsson, T. & Ek, W. E. (2022). Investigating the Effect of Estradiol Levels on the Risk of Breast, Endometrial, and Ovarian Cancer. Journal of the Endocrine Society, 6(8), Article ID bvac100.
Åpne denne publikasjonen i ny fane eller vindu >>Investigating the Effect of Estradiol Levels on the Risk of Breast, Endometrial, and Ovarian Cancer
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2022 (engelsk)Inngår i: Journal of the Endocrine Society, E-ISSN 2472-1972, Vol. 6, nr 8, artikkel-id bvac100Artikkel i tidsskrift (Fagfellevurdert) Published
Abstract [en]

Background: High levels of estrogen are associated with increased risk of breast and endometrial cancer and have been suggested to also play a role in the development of ovarian cancer. Cancerogenic effects of estradiol, the most prominent form of estrogen, have been highlighted as a side effect of estrogen-only menopausal hormone therapy. However, whether high levels of endogenous estrogens, produced within the body, promote cancer development, has not been fully established.

Objective: We aimed to examine causal effects of estradiol on breast, endometrial, and ovarian cancer.

Methods: Here we performed a two-sample Mendelian randomization (MR) to estimate the effect of endogenous estradiol on the risk of developing breast, endometrial, and ovarian cancer, using the UK Biobank as well as 3 independent cancer cohorts.

Results: Using 3 independent instrumental variables, we showed that higher estradiol levels significantly increase the risk for ovarian cancer (OR = 3.18 [95% CI, 1.47-6.87], P = 0.003). We also identified a nominally significant effect for ER-positive breast cancer (OR = 2.16 [95% CI, 1.09-4.26], P = 0.027). However, we could not establish a clear link to the risk of endometrial cancer (OR = 1.93 [95% CI, 0.77-4.80], P = 0.160).

Conclusion: Our results suggest that high estradiol levels promote the development of ovarian and ER-positive breast cancer.

sted, utgiver, år, opplag, sider
The Endocrine Society, 2022
Emneord
estradiol, ovarian cancer, breast cancer, endometrial cancer, Mendelian randomization
HSV kategori
Identifikatorer
urn:nbn:se:uu:diva-481664 (URN)10.1210/jendso/bvac100 (DOI)000822061300001 ()35822202 (PubMedID)
Forskningsfinansiär
Swedish Cancer Society, 21 0447 FESwedish Cancer Society, 19 0383 PjSwedish Research Council, 2019-01497M Borgströms stiftelse för ärftlighetsforskningK och O F Hedströms StiftelseÅke Wiberg Foundation, M19-0349Åke Wiberg Foundation, M20-0057Agnes and Mac Rudberg Foundation
Tilgjengelig fra: 2022-08-16 Laget: 2022-08-16 Sist oppdatert: 2023-12-06bibliografisk kontrollert
Johansson, T., Fowler, P., Ek, W. E., Skalkidou, A., Karlsson, T. & Johansson, Å. (2022). Oral Contraceptives, Hormone Replacement Therapy, and Stroke Risk. Stroke, 53(10), 3107-3115
Åpne denne publikasjonen i ny fane eller vindu >>Oral Contraceptives, Hormone Replacement Therapy, and Stroke Risk
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2022 (engelsk)Inngår i: Stroke, ISSN 0039-2499, E-ISSN 1524-4628, Vol. 53, nr 10, s. 3107-3115Artikkel i tidsskrift (Fagfellevurdert) Published
Abstract [en]

BACKGROUND: Millions of women worldwide use exogenous hormones as oral contraceptives or hormone replacement therapy. Still, time-dependent and long-term consequences of exogenous hormones on stroke risk remains unclear.

METHODS: We examined the association between self-reported oral contraceptive and hormone replacement therapy use and stroke risk in 257 194 women from the UK Biobank, born between 1939 and 1970. Outcomes included any type of stroke, ischemic stroke, intracerebral hemorrhage, and subarachnoid hemorrhage. Exposures were analyzed as time-varying variables in Cox regression models.

RESULTS: During first year of oral contraceptive use, an increased event rate of any stroke was observed (hazard ratio [HR], 2.49 [95% CI, 1.44-4.30]), while the hazards were found to be comparable during remaining years of use (HR, 1.00 [95% CI, 0.86-1.14]), compared with nonusers. Similarly, first year of hormone replacement therapy use was associated with higher hazard rates of any stroke (HR, 2.12 [95% CI, 1.66-2.70]), as well as cause-specific stroke, including ischemic stroke (HR, 1.93 [95% CI, 1.05-3.57]) and subarachnoid hemorrhage (HR, 2.17 [95% CI, 1.25-3.78]), which remained increased for any stroke during remaining years of use (HR, 1.18 [95% CI, 1.05-1.31]), and after discontinuation (HR, 1.16 [95% CI, 1.02-1.32]).

CONCLUSIONS: Oral contraceptive use and hormone replacement therapy were associated with an increased risk of stroke, especially during the first year of use, possibly due to immediate changes in hemostatic balance. This study provides new insights on the effects of hormone exposure on stroke risk and provide evidence of not only an overall risk but also a pronounced effects seen in the beginning of treatment.

sted, utgiver, år, opplag, sider
Lippincott Williams & Wilkins, 2022
HSV kategori
Forskningsprogram
Epidemiologi
Identifikatorer
urn:nbn:se:uu:diva-482558 (URN)10.1161/strokeaha.121.038659 (DOI)000856392500026 ()35735009 (PubMedID)
Forskningsfinansiär
The Swedish Brain FoundationSwedish Heart Lung FoundationSwedish Research Council
Merknad

De två sista författarna delar sistaförfattarskapet.

Tilgjengelig fra: 2022-08-24 Laget: 2022-08-24 Sist oppdatert: 2022-10-12bibliografisk kontrollert
Ek, W. E., Karlsson, T., Höglund, J., Rask-Andersen, M. & Johansson, Å. (2021). Causal effects of inflammatory protein biomarkers on inflammatory diseases. Science Advances, 7(50), Article ID eabl4359.
Åpne denne publikasjonen i ny fane eller vindu >>Causal effects of inflammatory protein biomarkers on inflammatory diseases
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2021 (engelsk)Inngår i: Science Advances, E-ISSN 2375-2548, Vol. 7, nr 50, artikkel-id eabl4359Artikkel i tidsskrift (Fagfellevurdert) Published
Abstract [en]

Many circulating proteins are associated with the presence or severity of disease. However, whether these protein biomarkers are causal for disease development is usually unknown. We investigated the causal effect of 21 well-known or exploratory protein biomarkers of inflammation on 18 inflammatory diseases using two-sample Mendelian randomization. We identified six proteins to have causal effects on any of 11 inflammatory diseases (FDR < 0.05, corresponding to P < 1.4 x 10(-3)). IL-12B protects against psoriasis and psoriatic arthropathy, LAP-TGF-beta-1 protects against osteoarthritis, TWEAK protects against asthma, VEGF-A protects against ulcerative colitis, and LT-alpha protects against both type 1 diabetes and rheumatoid arthritis. In contrast, IL-18R1 increases the risk of developing allergy, hay fever, and eczema. Most proteins showed protective effects against development of disease rather than increasing disease risk, which indicates that many disease-related biomarkers are expressed to protect from tissue damage. These proteins represent potential intervention points for disease prevention and treatment.

sted, utgiver, år, opplag, sider
American Association for the Advancement of Science (AAAS), 2021
HSV kategori
Forskningsprogram
Medicinsk vetenskap
Identifikatorer
urn:nbn:se:uu:diva-460813 (URN)10.1126/sciadv.abl4359 (DOI)000728174000018 ()34878845 (PubMedID)
Tilgjengelig fra: 2021-12-09 Laget: 2021-12-09 Sist oppdatert: 2024-01-15bibliografisk kontrollert
Höglund, J., Karlsson, T., Johansson, T., Ek, W. E. & Johansson, Å. (2021). Characterization of the human ABO genotypes and their association to common inflammatory and cardiovascular diseases in the UK Biobank. American Journal of Hematology, 96(11), 1350-1362
Åpne denne publikasjonen i ny fane eller vindu >>Characterization of the human ABO genotypes and their association to common inflammatory and cardiovascular diseases in the UK Biobank
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2021 (engelsk)Inngår i: American Journal of Hematology, ISSN 0361-8609, E-ISSN 1096-8652, Vol. 96, nr 11, s. 1350-1362Artikkel i tidsskrift (Fagfellevurdert) Published
Abstract [en]

The ABO gene contains three major alleles that encodes different antigens; A, B, and O, which determine an individual's blood group. Previous studies have primarily focused on identifying associations between ABO blood groups and diseases risk. Here, we sought to test for association between ABO genotypes (OO, OA, AA; OB, BB, and AB) and a large set of common inflammatory and cardiovascular diseases in UK Biobank as well as disease-related protein biomarkers in NSPHS. We first tested for association by conducting a likelihood ratio test, testing whether ABO contributed significantly to the risk for 24 diseases, and 438 plasma proteins. For phenotypes with FDR < 0.05, we tested for pair-wise differences between genetically determined ABO genotypes using logistic or linear regression. Our study confirmed previous findings of a strong association between ABO and cardiovascular disease, identified associations for both type 1 and type 2 diabetes, and provide additional evidence of significant differences between heterozygous and homozygous allele carriers for pulmonary embolism, deep vein thrombosis, but also for von Willebrand factor levels. Furthermore, the results indicated an additive effect between genotypes, even between the two most common A subgroups, A1 and A2. Additionally, we found that ABO contributed significantly to 39 plasma proteins, of which 23 have never been linked to the ABO locus before. These results show the need of incorporating ABO genotype information in the consultation and management of patients at risk, rather than classifying patients into blood groups.

sted, utgiver, år, opplag, sider
John Wiley & Sons, 2021
HSV kategori
Identifikatorer
urn:nbn:se:uu:diva-452185 (URN)10.1002/ajh.26307 (DOI)000686417700001 ()34329492 (PubMedID)
Forskningsfinansiär
Swedish Research Council, 2019-01497Swedish Heart Lung Foundation, 2020-0687Swedish Heart Lung Foundation, FO2020-0205Swedish Heart Lung Foundation, FO2019-0129
Tilgjengelig fra: 2021-09-03 Laget: 2021-09-03 Sist oppdatert: 2024-01-15bibliografisk kontrollert
Schmitz, D., Ek, W. E., Berggren, E., Höglund, J., Karlsson, T. & Johansson, Å. (2021). Genome-Wide Association Study of Estradiol Levels and the Causal Effect of Estradiol on Bone Mineral Density. Journal of Clinical Endocrinology and Metabolism, 106(11), e4471-e4486
Åpne denne publikasjonen i ny fane eller vindu >>Genome-Wide Association Study of Estradiol Levels and the Causal Effect of Estradiol on Bone Mineral Density
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2021 (engelsk)Inngår i: Journal of Clinical Endocrinology and Metabolism, ISSN 0021-972X, E-ISSN 1945-7197, Vol. 106, nr 11, s. e4471-e4486Artikkel i tidsskrift (Fagfellevurdert) Published
Abstract [en]

Context

Estradiol is the primary female sex hormone and plays an important role for skeletal health in both sexes. Several enzymes are involved in estradiol metabolism, but few genome-wide association studies (GWAS) have been performed to characterize the genetic contribution to variation in estrogen levels.

Objective

Identify genetic loci affecting estradiol levels and estimate causal effect of estradiol on bone mineral density (BMD).

Design

We performed GWAS for estradiol in males (n = 147 690) and females (n = 163 985) from UK Biobank. Estradiol was analyzed as a binary phenotype above/below detection limit (175 pmol/L). We further estimated the causal effect of estradiol on BMD using Mendelian randomization.

Results

We identified 14 independent loci associated (P < 5 × 10−8) with estradiol levels in males, of which 1 (CYP3A7) was genome-wide and 7 nominally (P < 0.05) significant in females. In addition, 1 female-specific locus was identified. Most loci contain functionally relevant genes that have not been discussed in relation to estradiol levels in previous GWAS (eg, SRD5A2, which encodes a steroid 5-alpha reductase that is involved in processing androgens, and UGT3A1 and UGT2B7, which encode enzymes likely to be involved in estradiol elimination). The allele that tags the O blood group at the ABO locus was associated with higher estradiol levels. We identified a causal effect of high estradiol levels on increased BMD in both males (P = 1.58 × 10−11) and females (P = 7.48 × 10−6).

Conclusion

Our findings further support the importance of the body’s own estrogen to maintain skeletal health in males and in females.

sted, utgiver, år, opplag, sider
Endocrine SocietyThe Endocrine Society, 2021
Emneord
Bone mineral density, Estrogen, GWAS, Mendelian Randomization
HSV kategori
Identifikatorer
urn:nbn:se:uu:diva-452186 (URN)10.1210/clinem/dgab507 (DOI)000715561700036 ()34255042 (PubMedID)
Forskningsfinansiär
Swedish Heart Lung Foundation, 20200687M Borgströms stiftelse för ärftlighetsforskningSwedish Research Council, 2019-01497The Swedish Brain Foundation, FO2020-0205The Swedish Brain Foundation, FO2019-0129Åke Wiberg FoundationAgnes and Mac Rudberg Foundation
Tilgjengelig fra: 2021-09-03 Laget: 2021-09-03 Sist oppdatert: 2024-01-15bibliografisk kontrollert
Organisasjoner
Identifikatorer
ORCID-id: ORCID iD iconorcid.org/0000-0003-2194-496x