Genome-wide polygenic risk score for retinopathy of type 2 diabetes

2021 ◽  
Author(s):  
Iain S Forrest ◽  
Kumardeep Chaudhary ◽  
Ishan Paranjpe ◽  
Ha My T Vy ◽  
Carla Marquez-Luna ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Risk Score ◽  
Large Scale ◽  
European Ancestry ◽  
Polygenic Risk Score ◽  
Standard Deviation Increase ◽  
Polygenic Risk ◽  
Genome Wide ◽  
A Genome

Abstract Diabetic retinopathy (DR) is a common consequence in type 2 diabetes (T2D) and a leading cause of blindness in working-age adults. Yet, its genetic predisposition is largely unknown. Here, we examined the polygenic architecture underlying DR by deriving and assessing a genome-wide polygenic risk score (PRS) for DR. We evaluated the PRS in 6079 individuals with T2D of European, Hispanic, African and other ancestries from a large-scale multi-ethnic biobank. Main outcomes were PRS association with DR diagnosis, symptoms and complications, and time to diagnosis, and transferability to non-European ancestries. We observed that PRS was significantly associated with DR. A standard deviation increase in PRS was accompanied by an adjusted odds ratio (OR) of 1.12 [95% confidence interval (CI) 1.04–1.20; P = 0.001] for DR diagnosis. When stratified by ancestry, PRS was associated with the highest OR in European ancestry (OR = 1.22, 95% CI 1.02–1.41; P = 0.049), followed by African (OR = 1.15, 95% CI 1.03–1.28; P = 0.028) and Hispanic ancestries (OR = 1.10, 95% CI 1.00–1.10; P = 0.050). Individuals in the top PRS decile had a 1.8-fold elevated risk for DR versus the bottom decile (P = 0.002). Among individuals without DR diagnosis, the top PRS decile had more DR symptoms than the bottom decile (P = 0.008). The PRS was associated with retinal hemorrhage (OR = 1.44, 95% CI 1.03–2.02; P = 0.03) and earlier DR presentation (10% probability of DR by 4 years in the top PRS decile versus 8 years in the bottom decile). These results establish the significant polygenic underpinnings of DR and indicate the need for more diverse ancestries in biobanks to develop multi-ancestral PRS.

1645-P: Polygenic Risk Score for Prediction of Complications in Men and Women with Type 2 Diabetes

Diabetes ◽  
2020 ◽  
Vol 69 (Supplement 1) ◽  
pp. 1645-P
Author(s):  
JOHANNE TREMBLAY ◽  
REDHA ATTAOUA ◽  
MOUNSIF HALOUI ◽  
RAMZAN TAHIR ◽  
CAROLE LONG ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Risk Score ◽  
Polygenic Risk Score ◽  
Men And Women ◽  
Polygenic Risk ◽  
Prediction Of Complications

304-OR: Polygenic Risk Score Predicts Type 2 Diabetes Susceptibility in a Diverse Consumer Genetic Database

Diabetes ◽  
2019 ◽  
Vol 68 (Supplement 1) ◽  
pp. 304-OR
Author(s):  
MICHAEL L. MULTHAUP ◽  
RYOSUKE KITA ◽  
NICHOLAS ERIKSSON ◽  
STELLA ASLIBEKYAN ◽  
JANIE SHELTON ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Risk Score ◽  
Polygenic Risk Score ◽  
Diabetes Susceptibility ◽  
Genetic Database ◽  
Polygenic Risk

1134-P: Polygenic Risk Score of Type 2 Diabetes as a Predictive Factor for Macrovascular Complications: A Prospective Population-Based UK Biobank Study

Diabetes ◽  
2021 ◽  
Vol 70 (Supplement 1) ◽  
pp. 1134-P
Author(s):  
SANGHYUK JUNG ◽  
DOKYOON KIM ◽  
MANU SHIVAKUMAR ◽  
HONG-HEE WON ◽  
JAE-SEUNG YUN
Keyword(s):  
Type 2 Diabetes ◽  
Risk Score ◽  
Predictive Factor ◽  
Population Based ◽  
Macrovascular Complications ◽  
Polygenic Risk Score ◽  
Uk Biobank ◽  
Polygenic Risk

Abstract PO-163: Genome-wide polygenic risk score of prostate cancer in African and European ancestry men

2022 ◽  
Author(s):  
Burcu F. Darst ◽  
Ravi K Madduri ◽  
Alexis A. Rodriguez ◽  
Xin Sheng ◽  
Rosalind A. Eeles ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Risk Score ◽  
European Ancestry ◽  
Polygenic Risk Score ◽  
Polygenic Risk ◽  
Genome Wide

scholarly journals Harnessing the power of polygenic risk scores to predict type 2 diabetes and its subtypes in a high-risk population of British Pakistanis and Bangladeshis in a routine healthcare setting

2021 ◽  
Author(s):  
Sam Hodgson ◽  
Qin Qin Huang ◽  
Neneh Sallah ◽  
Chris J Griffiths ◽  
William Newman ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
High Risk ◽  
European Ancestry ◽  
Risk Scores ◽  
P Value ◽  
High Risk Population ◽  
Polygenic Risk Score ◽  
Polygenic Risk ◽  
British Pakistanis

Background: Type 2 diabetes is a heterogeneous condition highly prevalent in British Pakistanis and Bangladeshis (BPB). The Genes & Health (G&H) cohort offers means to explore genetic determinants of disease in BPBs, combining genetic and lifelong health record data. Methods: We assessed whether common genetic loci associated with type 2 diabetes in European-ancestry individuals (EUR) replicate in G&H. We constructed a type 2 diabetes polygenic risk score (PRS) and combined it with a clinical risk instrument (QDiabetes) to build a novel, integrated risk tool (IRT). We compared IRT performance using net reclassification index (NRI) versus QDiabetes alone. We assessed the ability of the PRS to predict type 2 diabetes following gestational diabetes (GDM). We compared PRS distribution between type 2 diabetes subgroups identified by clinical features at diagnosis. Findings: Accounting for power, we replicated fewer loci associated with type 2 diabetes in G&H (n = 76/338, 22%) than would be expected if all EUR-ascertained loci were transferable (n = 95, 28%) (binomial p value = 0.01). In 13,648 patients free from type 2 diabetes followed up for 10 years, NRI was 3.2% for IRT versus QDiabetes (95% confidence interval 2.0 - 4.4%). IRT performance was best in reclassification of young adults deemed low risk by QDiabetes as high risk. PRS was independently associated with progression to type 2 diabetes after GDM (p = 0.028). Mean type 2 diabetes PRS differed between phenotypically-defined type 2 diabetes subgroups (p = 0.002). Interpretation: The type 2 diabetes PRS has broad potential clinical application in BPB, improving identification of type 2 diabetes risk (especially in the young), and characterisation of type 2 diabetes subgroups at diagnosis. Funding: Wellcome Trust, MRC, NIHR, and others. Full funding disclosed within.

scholarly journals Novel Common Genetic Susceptibility Loci for Colorectal Cancer

2018 ◽  
Vol 111 (2) ◽  
pp. 146-157 ◽  
Author(s):  
Stephanie L Schmit ◽  
Christopher K Edlund ◽  
Fredrick R Schumacher ◽  
Jian Gong ◽  
Tabitha A Harrison ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Relative Risk ◽  
Risk Score ◽  
European Ancestry ◽  
Polygenic Risk Score ◽  
Susceptibility Loci ◽  
Polygenic Risk ◽  
Control Subjects ◽  
Genome Wide ◽  
Familial Relative Risk

Abstract Background Previous genome-wide association studies (GWAS) have identified 42 loci (P < 5 × 10−8) associated with risk of colorectal cancer (CRC). Expanded consortium efforts facilitating the discovery of additional susceptibility loci may capture unexplained familial risk. Methods We conducted a GWAS in European descent CRC cases and control subjects using a discovery–replication design, followed by examination of novel findings in a multiethnic sample (cumulative n = 163 315). In the discovery stage (36 948 case subjects/30 864 control subjects), we identified genetic variants with a minor allele frequency of 1% or greater associated with risk of CRC using logistic regression followed by a fixed-effects inverse variance weighted meta-analysis. All novel independent variants reaching genome-wide statistical significance (two-sided P < 5 × 10−8) were tested for replication in separate European ancestry samples (12 952 case subjects/48 383 control subjects). Next, we examined the generalizability of discovered variants in East Asians, African Americans, and Hispanics (12 085 case subjects/22 083 control subjects). Finally, we examined the contributions of novel risk variants to familial relative risk and examined the prediction capabilities of a polygenic risk score. All statistical tests were two-sided. Results The discovery GWAS identified 11 variants associated with CRC at P < 5 × 10−8, of which nine (at 4q22.2/5p15.33/5p13.1/6p21.31/6p12.1/10q11.23/12q24.21/16q24.1/20q13.13) independently replicated at a P value of less than .05. Multiethnic follow-up supported the generalizability of discovery findings. These results demonstrated a 14.7% increase in familial relative risk explained by common risk alleles from 10.3% (95% confidence interval [CI] = 7.9% to 13.7%; known variants) to 11.9% (95% CI = 9.2% to 15.5%; known and novel variants). A polygenic risk score identified 4.3% of the population at an odds ratio for developing CRC of at least 2.0. Conclusions This study provides insight into the architecture of common genetic variation contributing to CRC etiology and improves risk prediction for individualized screening.

scholarly journals Polygenic risk for obesity and its interaction with lifestyle and sociodemographic factors in European children and adolescents

2021 ◽  
Author(s):  
Anke Hüls ◽  
Marvin N. Wright ◽  
Leonie H. Bogl ◽  
Jaakko Kaprio ◽  
Lauren Lissner ◽  
...  
Keyword(s):  
Children And Adolescents ◽  
Risk Score ◽  
Lifestyle Factors ◽  
Polygenic Risk Score ◽  
Genome Wide Association Studies ◽  
Genetic Liability ◽  
Level Of Education ◽  
Polygenic Risk ◽  
Genome Wide ◽  
A Genome

Abstract Background Childhood obesity is a complex multifaceted condition, which is influenced by genetics, environmental factors, and their interaction. However, these interactions have mainly been studied in twin studies and evidence from population-based cohorts is limited. Here, we analyze the interaction of an obesity-related genome-wide polygenic risk score (PRS) with sociodemographic and lifestyle factors for BMI and waist circumference (WC) in European children and adolescents. Methods The analyses are based on 8609 repeated observations from 3098 participants aged 2–16 years from the IDEFICS/I.Family cohort. A genome-wide polygenic risk score (PRS) was calculated using summary statistics from independent genome-wide association studies of BMI. Associations were estimated using generalized linear mixed models adjusted for sex, age, region of residence, parental education, dietary intake, relatedness, and population stratification. Results The PRS was associated with BMI (beta estimate [95% confidence interval (95%—CI)] = 0.33 [0.30, 0.37], r2 = 0.11, p value = 7.9 × 10−81) and WC (beta [95%—CI] = 0.36 [0.32, 0.40], r2 = 0.09, p value = 1.8 × 10−71). We observed significant interactions with demographic and lifestyle factors for BMI as well as WC. Children from Southern Europe showed increased genetic liability to obesity (BMI: beta [95%—CI] = 0.40 [0.34, 0.45]) in comparison to children from central Europe (beta [95%—CI] = 0.29 [0.23, 0.34]), p-interaction = 0.0066). Children of parents with a low level of education showed an increased genetic liability to obesity (BMI: beta [95%—CI] = 0.48 [0.38, 0.59]) in comparison to children of parents with a high level of education (beta [95%—CI] = 0.30 [0.26, 0.34]), p-interaction = 0.0012). Furthermore, the genetic liability to obesity was attenuated by a higher intake of fiber (BMI: beta [95%—CI] interaction = −0.02 [−0.04,−0.01]) and shorter screen times (beta [95%—CI] interaction = 0.02 [0.00, 0.03]). Conclusions Our results highlight that a healthy childhood environment might partly offset a genetic predisposition to obesity during childhood and adolescence.

scholarly journals Validation of a Trans-Ancestry Polygenic Risk Score for Type 2 Diabetes in Diverse Populations

2021 ◽  
Author(s):  
Tian Ge ◽  
Amit Patki ◽  
Vinodh Srinivasasainagendra ◽  
Yen-Feng Lin ◽  
Marguerite Ryan Irvin ◽  
...  
Keyword(s):  
Risk Factors ◽  
Type 2 Diabetes ◽  
African American ◽  
Large Scale ◽  
Association Studies ◽  
Risk Scores ◽  
Polygenic Risk Score ◽  
Genome Wide Association Studies ◽  
Polygenic Risk

ABSTRACTType 2 diabetes (T2D) is a worldwide scourge caused by both genetic and environmental risk factors that disproportionately afflicts communities of color. Leveraging existing large-scale genome-wide association studies (GWAS), polygenic risk scores (PRS) have shown promise to complement established clinical risk factors and intervention paradigms, and improve early diagnosis and prevention of T2D. However, to date, T2D PRS have been most widely developed and validated in individuals of European descent. Comprehensive assessment of T2D PRS in non-European populations is critical for an equitable deployment of PRS to clinical practice that benefits global populations. Here we integrate T2D GWAS in European, African American and East Asian populations to construct a trans-ancestry T2D PRS using a newly developed Bayesian polygenic modeling method, and evaluate the PRS in the multi-ethnic eMERGE study, four African American cohorts, and the Taiwan Biobank. The trans-ancestry PRS was significantly associated with T2D status across the ancestral groups examined, and the top 2% of the PRS distribution can identify individuals with an approximately 2.5-4.5 fold of increase in T2D risk, suggesting the potential of using the trans-ancestry PRS as a meaningful index of risk among diverse patients in clinical settings. Our efforts represent the first step towards the implementation of the T2D PRS into routine healthcare.

scholarly journals A genome-wide association and polygenic risk score study on abnormal electrocardiogram in a Chinese population

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Mengqiao Wang ◽  
Jiaqi Gao ◽  
Yang Shi ◽  
Xing Zhao
Keyword(s):  
Risk Score ◽  
Chinese Population ◽  
Genome Wide Association ◽  
Physical Parameters ◽  
Polygenic Risk Score ◽  
Polygenic Risk ◽  
Genome Wide ◽  
A Genome ◽  
Potential Biomarker ◽  
Increased Risk

AbstractElectrocardiography is a common and widely-performed medical examination based on the measurement and evaluation of electrocardiogram (ECG) to assess the up-to-date cardiac rhythms and thus suggest the health conditions of cardiovascular system and on a larger level the individual’s wellness. Abnormal ECG assessment from the detection of abnormal heart rhythms may have clinical implications including blood clots in formation, ongoing heart attack, coronary artery blockage, etc. Past genetic-phenotypic research focused primarily on the physical parameters of ECG but not the medical evaluation. To unbiasedly uncover the underlying links of genetic variants with normal vs. abnormal ECG assessment, a genome-wide association study (GWAS) is carried out in a 1006-participant cohort of Chinese population effectively genotyped for 243487 single nucleotide polymorphisms (SNPs). Both age and sex are influential factors, and six novel SNPs are identified for potential association with abnormal ECG. With the selected SNPs, a polygenic risk score (PRS) differentiates the case–control subgroups, and correlates well with increased risk of abnormal ECG. The findings are reproduced in an independent validation cohort. The derived PRS may function as a potential biomarker for prospectively screening the high-risk subgroup of heart issues in the Chinese population.

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