Sex-Stratified Polygenic Risk Score Identifies Individuals at Increased Risk of Basal Cell Carcinoma

AbstractBackgroundSchizophrenia is a highly heritable disorder, linked to several structural abnormalities of the brain. More specifically, previous findings have suggested that increased gyrification in frontal and temporal regions are implicated in the pathogenesis of schizophrenia.MethodsThe current study included participants at high familial risk of schizophrenia who remained well (n= 31), who developed sub-diagnostic symptoms (n= 28) and who developed schizophrenia (n= 9) as well as healthy controls (HC) (n= 16). We first tested whether individuals at high familial risk of schizophrenia carried an increased burden of trait-associated alleles using polygenic risk score analysis. We then assessed the extent to which polygenic risk was associated with gyral folding in the frontal and temporal lobes.ResultsWe found that individuals at high familial risk of schizophrenia who developed schizophrenia carried a significantly greater burden of risk-conferring variants for the disorder compared to those at high risk (HR) who developed sub-diagnostic symptoms or remained well and HC. Furthermore, within the HR cohort, there was a significant and positive association between schizophrenia polygenic risk score and bilateral frontal gyrification.ConclusionsThese results suggest that polygenic risk for schizophrenia impacts upon early neurodevelopment to confer greater gyral folding in adulthood and an increased risk of developing the disorder.

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A case-control study ofMC1Rvariants in Greek patients with basal cell carcinoma: increased risk independently of pigmentary characteristics

Experimental Dermatology ◽

10.1111/exd.12703 ◽

2015 ◽

Vol 24 (6) ◽

pp. 476-478 ◽

Cited By ~ 2

Author(s):

Clio Dessinioti ◽

Vana Sypsa ◽

Katerina Kypreou ◽

Gerasimos Dimisianos ◽

Elisavet Kodela ◽

...

Keyword(s):

Basal Cell Carcinoma ◽

Cell Carcinoma ◽

Basal Cell ◽

Case Control Study ◽

Case Control ◽

Increased Risk ◽

Control Study

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Increased Risk of Cutaneous Squamous Cell Carcinoma After Vismodegib Therapy for Basal Cell Carcinoma

JAMA Dermatology ◽

10.1001/jamadermatol.2015.4330 ◽

2016 ◽

Vol 152 (5) ◽

pp. 527 ◽

Cited By ~ 57

Author(s):

Shalini V. Mohan ◽

Julia Chang ◽

Shufeng Li ◽

A. Solomon Henry ◽

Douglas J. Wood ◽

...

Keyword(s):

Squamous Cell Carcinoma ◽

Basal Cell Carcinoma ◽

Cell Carcinoma ◽

Squamous Cell ◽

Basal Cell ◽

Cutaneous Squamous Cell Carcinoma ◽

Increased Risk

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Phenotypic Differences Between Polygenic and Monogenic Hypobetalipoproteinemia

Arteriosclerosis Thrombosis and Vascular Biology ◽

10.1161/atvbaha.120.315491 ◽

2020 ◽

Author(s):

Antoine Rimbert ◽

Xavier Vanhoye ◽

Dramane Coulibaly ◽

Marie Marrec ◽

Matthieu Pichelin ◽

...

Keyword(s):

Liver Injury ◽

Risk Score ◽

Clinical Care ◽

Liver Steatosis ◽

Genetic Diagnosis ◽

Density Lipoprotein ◽

Polygenic Risk Score ◽

Nonalcoholic Fatty Liver ◽

Polygenic Risk ◽

Increased Risk

Objective: Primary hypobetalipoproteinemia is characterized by LDL-C (low-density lipoprotein cholesterol) concentrations below the fifth percentile. Primary hypobetalipoproteinemia mostly results from heterozygous mutations in the APOB and PCSK9 genes, and a polygenic origin is hypothesized in the remaining cases. Hypobetalipoproteinemia patients present an increased risk of nonalcoholic fatty liver disease and steatohepatitis. Here, we compared hepatic alterations between monogenic, polygenic, and primary hypobetalipoproteinemia of unknown cause. Approach and Results: Targeted next-generation sequencing was performed in a cohort of 111 patients with hypobetalipoproteinemia to assess monogenic and polygenic origins using an LDL-C-dedicated polygenic risk score. Forty patients (36%) had monogenic hypobetalipoproteinemia, 38 (34%) had polygenic hypobetalipoproteinemia, and 33 subjects (30%) had hypobetalipoproteinemia from an unknown cause. Patients with monogenic hypobetalipoproteinemia had lower LDL-C and apolipoprotein B plasma levels compared with those with polygenic hypobetalipoproteinemia. Liver function was assessed by hepatic ultrasonography and liver enzymes levels. Fifty-nine percent of patients with primary hypobetalipoproteinemia presented with liver steatosis, whereas 21% had increased alanine aminotransferase suggestive of liver injury. Monogenic hypobetalipoproteinemia was also associated with an increased prevalence of liver steatosis (81% versus 29%, P <0.001) and liver injury (47% versus 0%) compared with polygenic hypobetalipoproteinemia. Conclusions: This study highlights the importance of genetic diagnosis in the clinical care of primary hypobetalipoproteinemia patients. It shows for the first time that a polygenic origin of hypobetalipoproteinemia is associated with a lower risk of liver steatosis and liver injury versus monogenic hypobetalipoproteinemia. Thus, polygenic risk score is a useful tool to establish a more personalized follow-up of primary hypobetalipoproteinemia patients.

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Clinico-Histological study of Basosquamous Carcinoma of the Skin

Journal of Biotechnology Research Center ◽

10.24126/jobrc.2012.6.2.210 ◽

2012 ◽

Vol 6 (2) ◽

pp. 3-8

Author(s):

Rafal Abdulrazak Al-Rawi

Keyword(s):

Squamous Cell Carcinoma ◽

Basal Cell Carcinoma ◽

Cell Carcinoma ◽

Squamous Cell ◽

Basal Cell ◽

Epithelial Membrane Antigen ◽

Histological Study ◽

Low Molecular Weight ◽

Increased Risk ◽

Clinical Records

asosquamous carcinoma is one of skin malignant tumor with features of both basal cell carcinoma and squamous cell carcinoma. It may behave more aggressively with an increased risk of recurrence and metastases. Investigations on the incidence, clinical, histological and immunohistochemical findings of basosquamous cell carcinoma in comparison with basal and squamous cell carcinoma were carried out. The clinical records of 3000 patients were reviewed from Razgary teaching hospital in Erbil from the period of 1-1-2008 to 1-1-2009 for the diagnosis of basosquamous carcinoma, basal and squamous cell carcinoma and an immunohistochemistry study was done to the basosquamous cell carcinoma.The incidence of basosquamous carcinoma is 8.82% among basal 63.24% and squamous cell carcinoma 27.94%. The commonest site is the nose and mostly occurs in patient over 50 years. Regarding immunohistochemical study of both epithelial membrane antigen (EMA) and low molecular weight keratin (LMWK) showed 5 positive cases out of 6 Basosquamous carcinoma cases. It was concluded that Basosquamous carcinoma incidence is less than that of basal and squamous cell carcinoma. The histological diagnosis of basosquamous carcinoma is confirmed by the use of LMWK and EMA immunohistochemical staining of the areas of both basal cell carcinoma area and squamous cell carcinoma area, respectively

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P.0580 A polygenic risk score predicts an increased risk of depression in mentally healthy young adults

European Neuropsychopharmacology ◽

10.1016/j.euroneuro.2021.10.547 ◽

2021 ◽

Vol 53 ◽

pp. S425-S426

Author(s):

A. Kazantseva ◽

Y. Davydova ◽

R. Enikeeva ◽

R. Mustafin ◽

M. Lobaskova ◽

...

Keyword(s):

Young Adults ◽

Risk Score ◽

Polygenic Risk Score ◽

Polygenic Risk ◽

Increased Risk

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Prostate cancer risk prediction using a polygenic risk score

Scientific Reports ◽

10.1038/s41598-020-74172-z ◽

2020 ◽

Vol 10 (1) ◽

Author(s):

Csilla Sipeky ◽

Kirsi M. Talala ◽

Teuvo L. J. Tammela ◽

Kimmo Taari ◽

Anssi Auvinen ◽

...

Keyword(s):

Prostate Cancer ◽

Risk Score ◽

Prostate Cancer Risk ◽

Population Based ◽

Polygenic Risk Score ◽

Polygenic Risk ◽

Randomised Study ◽

Additional Information ◽

Increased Risk ◽

Hereditary Factors

Abstract Hereditary factors have a strong influence on prostate cancer (PC) risk and poorer outcomes, thus stratification by genetic factors addresses a critical need for targeted PC screening and risk-adapted follow-up. In this Finnish population-based retrospective study 2283 clinically diagnosed and 455 screen-detected patients from the Finnish Randomised Study of Screening for Prostate Cancer (FinRSPC), 2400 healthy individuals have been involved. Individual genetic risk through establishment of a polygenic risk score based on 55 PC risk SNPs identified through the Finnish subset of the Collaborative Oncological Gene-Environment Study was assessed. Men with PC had significantly higher median polygenic risk score compared to the controls (6.59 vs. 3.83, P < 0.0001). The polygenic risk score above the control median was a significant predictor of PC (OR 2.13, 95% CI 1.90–2.39). The polygenic risk score predicted the risk of PC with an AUC of 0.618 (95% CI 0.60–0.63). Men in the highest polygenic risk score quartile were 2.8—fold (95% CI 2.4–3.30) more likely to develop PC compared with men in the lowest quartile. In the FinRSPC cohort, a significantly higher percentage of men had a PSA level of ≥ 4 ng/mL in polygenic risk score quartile four compared to quartile one (18.7% vs 8.3%, P < 0.00001). Adding the PRS to a PSA-only model contributed additional information in predicting PC in the FinRSPC model. Results strongly suggest that use of the polygenic risk score would facilitate the identification of men at increased risk for PC.

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Premalignant and Malignant Skin Lesions in Two Recipients of Vascularized Composite Tissue Allografts (Face, Hands)

Case Reports in Transplantation ◽

10.1155/2015/356459 ◽

2015 ◽

Vol 2015 ◽

pp. 1-4 ◽

Cited By ~ 8

Author(s):

Jean Kanitakis ◽

Palmina Petruzzo ◽

Aram Gazarian ◽

Sylvie Testelin ◽

Bernard Devauchelle ◽

...

Keyword(s):

Basal Cell Carcinoma ◽

Cell Carcinoma ◽

Basal Cell ◽

Immunosuppressive Treatment ◽

Premalignant Lesions ◽

Solid Organ ◽

Composite Tissue ◽

Disseminated Superficial Actinic Porokeratosis ◽

Increased Risk ◽

Malignant Lesions

Recipients of solid organ transplants (RSOT) have a highly increased risk for developing cutaneous premalignant and malignant lesions, favored by the lifelong immunosuppression. Vascularized composite tissue allografts (VCA) have been introduced recently, and relevant data are sparse. Two patients with skin cancers (one with basal cell carcinoma and one with squamous cell carcinomas) have been so far reported in this patient group. Since 2000 we have been following 9 recipients of VCA (3 face, 6 bilateral hands) for the development of rejection and complications of the immunosuppressive treatment. Among the 9 patients, one face-grafted recipient was diagnosed with nodular-pigmented basal cell carcinoma of her own facial skin 6 years after graft, and one patient with double hand allografts developed disseminated superficial actinic porokeratosis, a potentially premalignant dermatosis, on her skin of the arm and legs. Similar to RSOT, recipients of VCA are prone to develop cutaneous premalignant and malignant lesions. Prevention should be applied through sun-protective measures, regular skin examination, and early treatment of premalignant lesions.

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Polygenic Risk Score Prediction for Endometriosis

Frontiers in Reproductive Health ◽

10.3389/frph.2021.793226 ◽

2021 ◽

Vol 3 ◽

Author(s):

Kirstine Kloeve-Mogensen ◽

Palle Duun Rohde ◽

Simone Twisttmann ◽

Marianne Nygaard ◽

Kristina Magaard Koldby ◽

...

Keyword(s):

Risk Score ◽

Genome Wide Association Study ◽

Polygenic Risk Score ◽

Uk Biobank ◽

Standard Deviation Increase ◽

Polygenic Risk ◽

Clinical Risk ◽

Risk Variants ◽

Increased Risk ◽

The Uk

Endometriosis is a major health care challenge because many young women with endometriosis go undetected for an extended period, which may lead to pain sensitization. Clinical tools to better identify candidates for laparoscopy-guided diagnosis are urgently needed. Since endometriosis has a strong genetic component, there is a growing interest in using genetics as part of the clinical risk assessment. The aim of this work was to investigate the discriminative ability of a polygenic risk score (PRS) for endometriosis using three different cohorts: surgically confirmed cases from the Western Danish endometriosis referral Center (249 cases, 348 controls), cases identified from the Danish Twin Registry (DTR) based on ICD-10 codes from the National Patient Registry (140 cases, 316 controls), and replication analysis in the UK Biobank (2,967 cases, 256,222 controls). Patients with adenomyosis from the DTR (25 cases) and from the UK Biobank (1,883 cases) were included for comparison. The PRS was derived from 14 genetic variants identified in a published genome-wide association study with more than 17,000 cases. The PRS was associated with endometriosis in surgically confirmed cases [odds ratio (OR) = 1.59, p = 2.57× 10−7] and in cases from the DTR biobank (OR = 1.50, p = 0.0001). Combining the two Danish cohorts, each standard deviation increase in PRS was associated with endometriosis (OR = 1.57, p = 2.5× 10−11), as well as the major subtypes of endometriosis; ovarian (OR = 1.72, p = 6.7× 10−5), infiltrating (OR = 1.66, p = 2.7× 10−9), and peritoneal (OR = 1.51, p = 2.6 × 10−3). These findings were replicated in the UK Biobank with a much larger sample size (OR = 1.28, p < 2.2× 10−16). The PRS was not associated with adenomyosis, suggesting that adenomyosis is not driven by the same genetic risk variants as endometriosis. Our results suggest that a PRS captures an increased risk of all types of endometriosis rather than an increased risk for endometriosis in specific locations. Although the discriminative accuracy is not yet sufficient as a stand-alone clinical utility, our data demonstrate that genetics risk variants in form of a simple PRS may add significant new discriminatory value. We suggest that an endometriosis PRS in combination with classical clinical risk factors and symptoms could be an important step in developing an urgently needed endometriosis risk stratification tool.

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Effect of APOE and a polygenic risk score on incident dementia and cognitive decline in a healthy older population

10.1101/2020.10.11.20210963 ◽

2020 ◽

Author(s):

Moeen Riaz ◽

Aamira Huq ◽

Joanne Ryan ◽

Suzanne G Orchard ◽

Jane Tiller ◽

...

Keyword(s):

Relative Risk ◽

Cognitive Decline ◽

Risk Score ◽

Cumulative Incidence ◽

Genetic Factors ◽

Polygenic Risk Score ◽

Older Individuals ◽

Polygenic Risk ◽

Increased Risk ◽

Incidence Of Dementia

AbstractImportanceFew studies have measured the effect of genetic factors on dementia and cognitive decline in a population of healthy older individuals followed prospectively.ObjectiveTo examine the effect of Apolipoprotein E (APOE) genotypes and a polygenic risk score (PRS) on incident dementia and cognitive decline in a longitudinal cohort of healthy older people.Design, Setting and ParticipantsPost-hoc genetic analysis of a randomized clinical trial population - the ASPirin in Reducing Events in the Elderly (ASPREE) trial. At enrollment, participants had no history of diagnosed dementia, atherothrombotic cardiovascular disease, or permanent physical disability and were without cognitive impairment.Main Outcomes and MeasuresDementia (adjudicated trial endpoint) and cognitive decline, defined as a >1.5 standard deviation decline in test score for either global cognition, episodic memory, language/executive function or psychomotor speed, versus baseline scores. Cumulative incidence curves for all-cause dementia and cognitive decline were calculated with mortality as a competing event, stratified by APOE genotypes and tertiles of a PRS based on 23 common non-APOE variants.Results12,978 participants with European ancestry were included; 54.8% were female, and average age at baseline was 75 years (range 70 to 96). During a median 4.5 years of follow-up, 324 (2.5%) participants developed dementia and 503 (3.8%) died. Cumulative incidence of dementia to age 85 years was estimated to be 7.4% in all participants, 12.6% in APOE ε4 heterozygotes, 26.6% in ε4 homozygotes, 9.6% in the high PRS tertile, and 7.3% in the low PRS tertile. APOE ε4 heterozygosity/homozygosity was associated with a 2.5/6.3-fold increased risk of dementia and a 1.4/1.8-fold increased risk of cognitive decline, versus ε3/ε3 (P<0.001 for both). A high PRS (top tertile) was associated with a 1.4-fold increase risk of dementia, versus the low tertile (CI 1.04-1.76, P=0.02), but was not associated with cognitive decline risk (CI 0.96-1.22, P = 0.18).Conclusions and RelevanceIncidence of dementia among healthy older individuals is low across all genotypes; however, APOE ε4 and high PRS increase relative risk. APOE ε4 is associated with cognitive decline, but PRS is not.KEY POINTSQuestionHow do genetic factors influence the risk of dementia and cognitive decline among healthy older individuals?FindingsWe studied cumulative incidence of dementia and cognitive decline in 12,978 healthy older individuals without cardiovascular disease or cognitive impairment at enrollment, stratified by APOE genotype and a polygenic risk score (PRS). APOE ε4 and PRS increased the relative risk of dementia, but cumulative incidence was low across all genotypes. APOE genotypes were associated with cognitive decline, but PRS was not.MeaningIncidence of dementia is low among healthy older individuals; however, genetic factors still increase relative risk.

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