scholarly journals 0016 Genetic Basis of Daytime Napping and Consequence on Cardiometabolic Health

SLEEP ◽  
2020 ◽  
Vol 43 (Supplement_1) ◽  
pp. A7-A7
Author(s):  
H S Dashti ◽  
I Daghlas ◽  
J Lane ◽  
M Udler ◽  
M Garaulet ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Waist Circumference ◽  
Health Outcomes ◽  
Association Study ◽  
Genetic Basis ◽  
Biological Pathways ◽  
European Ancestry ◽  
Cardiometabolic Health ◽  
Genome Wide ◽  
Cardiometabolic Traits

Abstract Introduction Although daytime napping is a common, evolutionarily conserved behavior, its genetic basis is unknown. Elucidating its genetic basis may clarify relevant underlying biological pathways and determine causal links with cardiometabolic health. Methods We performed a genome-wide association study of self-reported daytime napping using linear regression in adults of European ancestry in the UK Biobank (n=452,633) and assessed robustness of signals with accelerometer-derived daytime inactivity duration (n=84,671). Next, we conducted a phenome-wide association study in a hospital-based clinical biobank (n=30,683) using napping genome-wide polygenic score (GPS), and Mendelian randomization (MR) with cardiometabolic traits. To deconstruct the napping genetic variants, we applied a novel “soft clustering” Bayesian nonnegative matrix factorization method and generated partitioned cluster-specific polygenic risk scores (PRS). Results We identified 121 distinct genome-wide significant loci for daytime napping, with lead signals at or near genes KSR2 (kinase-suppressor of ras 2), HCRTR1/HCRTR2 (hypocretin-receptor 1/2), SKOR2 (SKI family transcriptional-corepressor 2), and MAPT (microtubule-associated protein tau), among others. The loci associated with accelerometer-derived daytime inactivity duration. Gene enrichment analyses pointed to pathways involved in neurogenesis and others including nervous system development and opioid signaling. Genetic overlaps were evident in a clinical biobank where highest, compared to lowest, decile of napping GPS associated with 30%, 40%, and 50% higher odds for essential hypertension, obesity, and nonalcoholic liver disease, respectively (P<0.0001). In MR, potential causal links were identified with higher diastolic blood pressure (2.67 mmHg per napping category-increase, 95% CI 1.62–3.23, P=6.80e-07), systolic blood pressure (3.65mmHg, 1.86–5.44, P=6.40e-05), and waist circumference (0.28 SD-units, 0.11–0.45, P=0.0015). The clustering of variants identified 3 robust clusters (cluster-1: “higher sleep propensity”; cluster-2: “more fragmented/inefficient night sleep”; cluster-3: “early sleep timing”). Only clusters 2 and 3 PRSs were associated with worse cardiometabolic health outcomes, including higher BMI, waist circumference, CRP, and triglycerides (all P<0.05). Conclusion These findings expand our understanding of the genetic architecture of napping implicating multiple biological pathways, indicating possible genetic overlap and causal links to cardiometabolic traits, and suggesting distinct nap-promoting mechanisms with differential associations with health outcomes. Support This work is supported by grants NIH-F32DK102323, NIH-4T32HL007901, NIH-R01DK107859, NIH-R35HL135818, and MGH Research Scholar Fund.

scholarly journals Genome-wide association study of problematic opioid prescription use in 132,113 23andMe research participants of European ancestry

2021 ◽  
Author(s):  
Sandra Sanchez-Roige ◽  
Pierre Fontanillas ◽  
Mariela V. Jennings ◽  
Sevim B. Bianchi ◽  
Yuye Huang ◽  
...  
Keyword(s):  
Association Study ◽  
Risk Taking ◽  
Genetic Basis ◽  
Genome Wide Association Study ◽  
Genetic Correlations ◽  
Genome Wide Association ◽  
European Ancestry ◽  
Opioid Use ◽  
Research Participants ◽  
Genome Wide

AbstractThe growing prevalence of opioid use disorder (OUD) constitutes an urgent health crisis. Ample evidence indicates that risk for OUD is heritable. As a surrogate (or proxy) for OUD, we explored the genetic basis of using prescription opioids ‘not as prescribed’. We hypothesized that misuse of opiates might be a heritable risk factor for OUD. To test this hypothesis, we performed a genome-wide association study (GWAS) of problematic opioid use (POU) in 23andMe research participants of European ancestry (N = 132,113; 21% cases). We identified two genome-wide significant loci (rs3791033, an intronic variant of KDM4A; rs640561, an intergenic variant near LRRIQ3). POU showed positive genetic correlations with the two largest available GWAS of OUD and opioid dependence (rg = 0.64, 0.80, respectively). We also identified numerous additional genetic correlations with POU, including alcohol dependence (rg = 0.74), smoking initiation (rg = 0.63), pain relief medication intake (rg = 0.49), major depressive disorder (rg = 0.44), chronic pain (rg = 0.42), insomnia (rg = 0.39), and loneliness (rg = 0.28). Although POU was positively genetically correlated with risk-taking (rg = 0.38), conditioning POU on risk-taking did not substantially alter the magnitude or direction of these genetic correlations, suggesting that POU does not simply reflect a genetic tendency towards risky behavior. Lastly, we performed phenome- and lab-wide association analyses, which uncovered additional phenotypes that were associated with POU, including respiratory failure, insomnia, ischemic heart disease, and metabolic and blood-related biomarkers. We conclude that opioid misuse can be measured in population-based cohorts and provides a cost-effective complementary strategy for understanding the genetic basis of OUD.

scholarly journals Genetic determinants of daytime napping and effects on cardiometabolic health

2020 ◽  
Author(s):  
Hassan S. Dashti ◽  
Iyas Daghlas ◽  
Jacqueline M. Lane ◽  
Yunru Huang ◽  
Miriam S. Udler ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Drug Targets ◽  
Genetic Basis ◽  
Genome Wide Association Study ◽  
Mendelian Randomization ◽  
Cardiometabolic Health ◽  
Genetic Determinants ◽  
Genome Wide ◽  
A Genome ◽  
The Uk

AbstractDaytime napping is a common, heritable behavior, but its genetic basis and causal relationship with cardiometabolic health remains unclear. Here, we performed a genome-wide association study of self-reported daytime napping in the UK Biobank (n=452,633) and identified 123 loci of which 60 replicated in 23andMe research participants (n=541,333). Findings included missense variants in established drug targets (HCRTR1, HCRTR2), genes with roles in arousal (TRPC6, PNOC), and genes suggesting an obesity-hypersomnolence pathway (PNOC, PATJ). Signals were concordant with accelerometer-measured daytime inactivity duration and 33 signals colocalized with signals for other sleep phenotypes. Cluster analysis identified 3 clusters suggesting distinct nap-promoting mechanisms with heterogeneous associations with cardiometabolic outcomes. Mendelian randomization showed potential causal links between more frequent daytime napping and higher systolic blood pressure, diastolic blood pressure, and waist circumference.

scholarly journals Genome-wide association study of problematic opioid prescription use in 132,113 23andMe research participants of European ancestry

2021 ◽  
Author(s):  
Sandra Sanchez-Roige ◽  
Pierre Fontanillas ◽  
Mariela V Jennings ◽  
Sevim Bianchi ◽  
Yuye Huang ◽  
...  
Keyword(s):  
Association Study ◽  
Risk Taking ◽  
Genetic Basis ◽  
Genome Wide Association Study ◽  
Genetic Correlations ◽  
Genome Wide Association ◽  
European Ancestry ◽  
Opioid Use ◽  
Research Participants ◽  
Genome Wide

Rates of opioid use disorder (OUD) constitute an urgent health crisis. Ample evidence indicates that risk for OUD is heritable. As a surrogate (or proxy) for OUD, we explored the genetic basis of using opioids "not as prescribed". We hypothesized that misuse of opiates might be a heritable risk factor for OUD. To test this hypothesis, we performed a genome-wide association study (GWAS) of problematic opioid use (POU; "ever taking opioid prescriptions not as prescribed") in 132,113 23andMe research participants of European ancestry (Ncases=27,805). Our GWAS identified two genome-wide significant loci (rs3791033, an intronic variant of KDM4A; rs640561, an intergenic variant near LRRIQ3). POU showed a positive genetic correlation with opioid dependence and OUD, as measured in the largest available GWAS (rg=0.57-0.80). We also identified numerous additional genetic correlations with POU, including alcohol dependence (rg=0.74), smoking initiation (rg=0.63), pain relief medication intake (rg=0.49), major depressive disorder (rg=0.44), chronic pain (rg=0.42), insomnia (rg=0.39), and loneliness (rg=0.28). Although POU was positively genetically correlated with risk-taking (rg=0.38), conditioning POU on risk-taking did not substantially alter the magnitude or direction of these genetic correlations, suggesting that POU does not simply reflect a general tendency for risky behavior. We conclude that opioid misuse can be measured in population-based cohorts and provides a cost-effective complementary strategy for understanding the genetic basis of OUD.

scholarly journals A Genome-Wide Association Study for Hypertensive Kidney Disease in Korean Men

Genes ◽  
2021 ◽  
Vol 12 (5) ◽  
pp. 751
Author(s):  
Hye-Rim Kim ◽  
Hyun-Seok Jin ◽  
Yong-Bin Eom
Keyword(s):  
Blood Pressure ◽  
Kidney Disease ◽  
Association Study ◽  
Genome Wide Association Study ◽  
Genome Wide Association ◽  
Integrated Analysis ◽  
Eqtl Analysis ◽  
Strong Linkage Disequilibrium ◽  
Genome Wide ◽  
A Genome

Hypertension is one of the major risk factors for chronic kidney disease (CKD), and the coexistence of hypertension and CKD increases morbidity and mortality. Although many genetic factors have been identified separately for hypertension and kidney disease, studies specifically focused on hypertensive kidney disease (HKD) have been rare. Therefore, this study aimed to identify loci or genes associated with HKD. A genome-wide association study (GWAS) was conducted using two Korean cohorts, the Health Examinee (HEXA) and Korean Association REsource (KARE). Consequently, 19 single nucleotide polymorphisms (SNPs) were found to be significantly associated with HKD in the discovery and replication phases (p < 5 × 10−8, p < 0.05, respectively). We further analyzed HKD-related traits such as the estimated glomerular filtration rate (eGFR), creatinine, blood urea nitrogen (BUN), systolic blood pressure (SBP) and diastolic blood pressure (DBP) at the 14q21.2 locus, which showed a strong linkage disequilibrium (LD). Expression quantitative trait loci (eQTL) analysis was also performed to determine whether HKD-related SNPs affect gene expression changes in glomerular and arterial tissues. The results suggested that the FANCM gene may affect the development of HKD through an integrated analysis of eQTL and GWAS and was the most significantly associated candidate gene. Taken together, this study indicated that the FANCM gene is involved in the pathogenesis of HKD. Additionally, our results will be useful in prioritizing other genes for further experiments.

Abstract P629: Genome-Wide Association Study of Individuals of Native Hawaiian Ancestry Reveals Unique Genetic Risk Factors for Stroke and Myocardial Infarction

Stroke ◽  
2021 ◽  
Vol 52 (Suppl_1) ◽  
Author(s):  
Stacy C Brown ◽  
Cameron Both ◽  
Julian N Acosta ◽  
Natalia Szejko ◽  
Victor Torres ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Ischemic Stroke ◽  
Association Study ◽  
Genome Wide Association Study ◽  
Native Hawaiian ◽  
European Ancestry ◽  
Intronic Region ◽  
Genome Wide ◽  
A Genome ◽  
Risk Locus

Background: Several genetic susceptibility risk loci for ischemic stroke have been identified. However, the relative dearth of genetic data from populations of non-European ancestry has the potential to create disparities in access to genomics-based precision medicine strategies. Individuals of Native Hawaiian ancestry represent a particularly understudied group in stroke genomics research despite facing high rates of cerebrovascular disease. Hypothesis: Genetic variants associated with stroke differ between Native Hawaiians and previously studied groups of predominantly European ancestry. Methods: We conducted a genome-wide (GW) association study of stroke and myocardial infarction (MI) in an adult population of Native Hawaiian ancestry, using data from the Multiethnic Cohort study (MEC). Genetic information was ascertained via genome-wide array genotyping using the AB OpenArray and TaqMan platforms followed by imputation to 1000 Genomes reference panels. We pursued replication of variants that were GW significant (p<5x10 -8 ) or yielded suggestive associations (p<5x10 -7 ) in the prior stroke GW association study MEGASTROKE. Results: We identified 2,104 individuals (1,089 [51.8%] female) of Native Hawaiian ancestry, including 173 cases and 1,931 controls. We identified one novel susceptibility risk locus at a narrow intronic region located at chromosome q26.2 (top associated SNP 3:169096251, OR 2.48, 95%CI 1.81-3.41; p=1.93x10 -8 ), overlying the MECOM gene. We also identified 9 other suggestive risk loci at p<5x10 -7 . When replicating in MEGASTROKE, q26.2 did not have available counterpart variants to analyze, and 3 out of 9 suggestive signals were associated with ischemic stroke subtypes at p<0.05. Conclusions: We report the first GW association study of ischemic stroke and myocardial infarction in a Native Hawaiian population. We identified one susceptibility risk locus at q26.2, located in a narrow intronic region of MECOM, a gene that codes for a histone-lysine N-methyltransferase that has transcriptional regulation and oncoprotein functions. The lack of available replication data for this locus in the large MEGASTROKE collaboration emphasizes the importance of developing genomic resources across ancestral groups.

scholarly journals Genome-wide association study identifies eight loci associated with blood pressure

2009 ◽  
Vol 41 (6) ◽  
pp. 666-676 ◽  
Author(s):  
Christopher Newton-Cheh ◽  
◽  
Toby Johnson ◽  
Vesela Gateva ◽  
Martin D Tobin ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Association Study ◽  
Genome Wide Association Study ◽  
Genome Wide Association ◽  
Genome Wide

scholarly journals Genome-Wide Association Study (GWAS) For Cold Tolerance at The Bud Burst Stage in Rice Using SNP Markers

2021 ◽  
Author(s):  
Caijing Li ◽  
Jindong Liu ◽  
Jianxin Bian ◽  
Tao Jin ◽  
Baoli Zou ◽  
...  
Keyword(s):  
Low Temperature ◽  
Association Study ◽  
Cold Tolerance ◽  
Genetic Basis ◽  
Genome Wide Association Study ◽  
Genome Wide Association ◽  
Bud Burst ◽  
Rice Varieties ◽  
Rice Landraces ◽  
Genome Wide

Abstract Background: Rice is a crop that is very sensitive to low temperature, and its morphological development and production are greatly affected by low temperature. Therefore, understanding the genetic basis of cold tolerance in rice is of great significance for mining favorable genes and cultivating excellent rice varieties. However, there were limited studies focusing on cold tolerance at the bud burst stage, therefore, considerable attention should be paid to the genetic basis of cold tolerance at the bud burst stage (CTBB).Results: In this study, a natural population consisting of 211 rice landraces collected from 15 provinces of China and other countries were firstly used to evaluate the cold tolerance at the bud burst stage. Population structure analysis showed that this population divided into three groups and was rich in genetic diversity. Our evaluation results confered that the japonica rice was more tolerance to cold at the bud burst stage than indica rice. Genome-wide association study (GWAS) were performed through the phenotypic data of 211 rice landraces and 36,727 SNPs dataset under a mixed linear model, and 12 QTLs (P < 0.0001) were identified according to the seedling survival rate (SSR) treated at 4 ℃, in which there are five QTLs (qSSR2-2, qSSR3-1, qSSR3-2, qSSR3-3 and qSSR9) which were co-located with previous studies, and seven QTLs (qSSR2-1, qSSR3-4, qSSR3-5, qSSR3-6, qSSR3-7, qSSR4 and qSSR7) which were reported for the first time. Among these QTLs, qSSR9, harboring the highest-peak SNP, explained biggest phenotypic variation. Through bioinformatics analysis, five genes (LOC_Os09g12440, LOC_Os09g12470, LOC_Os09g12520, LOC_Os09g12580 and LOC_Os09g12720) were nominated as candidates for qSSR9. Conclusion: This natural population consisting of 211 rice landraces with high density SNPs will serve as a better choice for identifying rice QTLs/genes in future, and the detected QTLs associated with cold tolerance in rice bud burst stage will be conducive to further mining favorable genes and breeding of rice varieties under cold stress.

scholarly journals Genome-wide Association Study of Pancreatic Fat: The Multiethnic Cohort Adiposity Phenotype Study

2021 ◽  
Author(s):  
Samantha Streicher ◽  
Unhee Lim ◽  
S. Lani Park ◽  
Yuqing Li ◽  
Xin Sheng ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Association Study ◽  
Genome Wide Association Study ◽  
Genome Wide Association ◽  
European Ancestry ◽  
American Population ◽  
Pancreatic Fat ◽  
Genome Wide ◽  
Multiethnic Cohort

Several studies have found associations between higher pancreatic fat content and adverse health outcomes, such as diabetes and the metabolic syndrome, but investigations into the genetic contributions to pancreatic fat are limited.  This genome-wide association study, comprised of 804 participants with MRI-assessed pancreatic fat measurements, was conducted in the ethnically diverse Multiethnic Cohort-Adiposity Phenotype Study (MEC-APS).  Two genetic variants reaching genome-wide significance, rs73449607 on chromosome 13q21.2 (Beta = -0.67, P = 4.50x10 -8 ) and rs7996760 on chromosome 6q14 (Beta = -0.90, P = 4.91x10 -8 ) were associated with percent pancreatic fat on the log scale.  Rs73449607 was most common in the African American population (13%) and rs79967607 was most common in the European American population (6%).  Rs73449607 was also suggestively associated with lower risk of type 2 diabetes (OR = 0.95, 95% CI = 0.89-1.00, P = 0.047) in the Population Architecture Genomics and Epidemiology (PAGE) Study and the DIAbetes Genetics Replication and Meta-analysis (DIAGRAM), which included substantial numbers of non-European ancestry participants (53,102 cases and 193,679 controls).  Rs73449607 is located in an intergenic region between GSX1 and PLUT , and rs79967607 is in intron 1 of EPM2A .  PLUT, a linkRNA, regulates transcription of an adjacent gene, PDX1 , that controls beta-cell function in the mature pancreas, and EPM2A encodes the protein laforin, which plays a critical role in regulating glycogen production.  If validated, these variants may suggest a genetic component for pancreatic fat and a common etiologic link between pancreatic fat and type 2 diabetes.

Abstract P221: Metabolic Syndrome And Its Factors Associate With Non-calcified Coronary Plaque Burden In Chronic Inflammation: Results From A Prospective Observational Study

Circulation ◽  
2021 ◽  
Vol 143 (Suppl_1) ◽  
Author(s):  
Meron Teklu ◽  
Wunan Zhou ◽  
Nidhi Patel ◽  
Grigory Manyak ◽  
Amit K Dey ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Metabolic Syndrome ◽  
Waist Circumference ◽  
Fasting Glucose ◽  
Coronary Plaque ◽  
Lipid Lowering ◽  
Plaque Burden ◽  
Cardiometabolic Health ◽  
Lipid Lowering Therapy ◽  
Early Atherosclerosis

Introduction: Psoriasis is a common, inflammatory skin disease associated with systemic inflammation and heightened risk of cardiovascular diseases (CVD). Population studies have shown that psoriasis is associated with metabolic syndrome (MetSyn) and its individual components. However, the impact of MetSyn on early atherosclerosis in chronic inflammatory diseases assessed as non-calcified coronary plaque burden (NCB) by coronary computed CT angiography (CCTA) is not known. Hypothesis: We hypothesized that those with MetSyn in psoriasis would have increased NCB compared to non-MetSyn and that MetSyn and its components would associate with NCB in fully adjusted models. Methods: The cohort consisted of 336 psoriasis patients free of cardiovascular disease, of which 326 had adequate data to classify MetSyn based on the International Diabetes Federation criteria (waist circumference, triglycerides, HDL cholesterol, blood pressure and fasting glucose). Of these, 260 had quantitative CCTA data available for analyses (Stata 16). Results: Of the 260 patients, 80 had MetSyn (31%). The MetSyn group had increased cardiometabolic disease and more adverse coronary characteristics including higher non-calcified ( p <.001) and high-risk plaque ( p =.02) (Table) . In fully adjusted models for Framingham risk score, lipid lowering therapy and biologic use, MetSyn (β=0.31; p< .001) and its individual components of waist circumference (β=0.33; p <.001), triglycerides (β=0.17; p =.005), blood pressure (β=0.18; p =.005) and fasting glucose (β=0.17; p =.009) associated with NCB. Conclusions: MetSyn and its components were associated with NCB in psoriasis suggesting that early atherosclerosis is importantly impacted by poor cardiometabolic health. Components of MetSyn should be assessed in psoriasis patients and patients educated about this heightened risk of CVD associated with MetSyn.

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