Try a new search

Format these results:

Searched for:

Department/Unit:Population Health

Total Results:

13264


Smoking Cessation among Female and Male Veterans before and after a Randomized Trial of Proactive Outreach

Danan, Elisheva R; Sherman, Scott E; Clothier, Barbara A; Burgess, Diana J; Pinsker, Erika A; Joseph, Anne M; Noorbaloochi, Siamak; Fu, Steven S
INTRODUCTION/BACKGROUND:Female veterans smoke cigarettes at high rates compared with both male veterans and nonveteran women. Proactive outreach to smokers may reduce gender disparities in cessation care. The objectives of this study were to compare baseline experiences with VA smoking cessation care for men and women and to assess for gender differences in response to a proactive outreach intervention. METHODS:We conducted a post hoc subgroup analysis of a pragmatic, multisite randomized, controlled trial comparing proactive outreach with usual care (UC). Baseline experiences included physician advice to quit, satisfaction with care, and past-year treatment use. At the 1-year follow-up, treatment use, quit attempts, and 6-month prolonged abstinence for women and men randomized to proactive outreach versus UC were compared using logistic regression. RESULTS:Baseline and follow-up surveys were returned by 138 women and 2,516 men. At baseline, women were less likely than men to report being very or somewhat satisfied with the process of obtaining smoking cessation medications in the VA (47% of women vs. 62% of men), but no less likely to report having used cessation medications from the VA in the past year (39% of women vs. 34% of men). After the intervention, phone counseling and combined therapy increased among both women and men in proactive outreach as compared with UC. At the 1-year follow-up, men in proactive outreach were significantly more likely to report prolonged abstinence than those in UC (odds ratio, 1.65; 95% CI, 1.28-2.14); results for women were in the same direction but not statistically significant (odds ratio, 1.39; 95% CI, 0.48-3.99). CONCLUSIONS:Satisfaction with cessation care in VA remains low. Proactive outreach to smokers was associated with an increased use of cessation therapies, and increased odds of achieving prolonged abstinence. A subgroup analysis by gender did not reveal significant differences in the treatment effect.
PMID: 31253237
ISSN: 1878-4321
CID: 3961252

Health Literacy in the Inpatient Setting: Implications for Patient Care and Patient Safety

Glick, Alexander F; Brach, Cindy; Yin, Hsiang Shonna; Dreyer, Benard P
Health literacy plays a role in the events leading up to children's hospitalizations, during hospital admission, and after discharge. Hospitals and providers should use a universal precautions approach and routinely incorporate health-literacy-informed strategies in communicating with all patients and families to ensure that they can understand health information, follow medical instructions, participate actively in their own/their child's care, and successfully navigate the health care system. Interventions that incorporate health-literacy-informed strategies and that target patients/families and health care systems should be implemented to improve patient outcomes and patient-centered and family-centered care.
PMID: 31230624
ISSN: 1557-8240
CID: 3943532

Racial Disparities in Nutritional Risk and Its Association with Chronic Disease and Health Outcomes Among Community-Dwelling Older Adults in the Adult Day Health Setting (P04-121-19)

Sadarangani, Tina; Missaelides, Lydia; Brody, Abraham; Trinh-Shevrin, Chau
Objectives/UNASSIGNED:Adult day health centers (ADHCs) serve >260,000 chronically ill individuals annually and are a preferred long-term care source for racial minorities, who also experience diet related disparities. Evidence regarding prevalence of nutritional risk is needed to inform dietary intervention planning in ADHCs. This study (1) identified prevalence of nutritional risk and associated factors, in a diverse sample of older ADHC users, (2) stratified differences in nutritional risk by race, and (3) explored associations between nutritional risk, chronic illness, and healthcare utilization. Methods/UNASSIGNED: < .05) differences among White Non-Hispanics, Blacks, Hispanics, and Asians aged >50. Bivariate chi-square tests were used to explore associations between nutritional risk and chronic disease, as well as healthcare utilization. Results/UNASSIGNED: = .01) were significant. Among blacks, 76.5% ate < 5 servings of fruits, vegetables, or milk daily, compared to 39.5% of whites; 21% of blacks ate <2 meals a day, compared to 2% of whites and Hispanics. Blacks (48.5%) more often reported involuntary weight loss/gain compared to whites (23.3%), and had the highest prevalence of tooth loss/mouth pain (41.2%) of any racial group. Conclusions/UNASSIGNED:Older adults in ADHCs are at elevated risk of malnutrition, and blacks disproportionately so. Routine nutritional screening in ADHCs should be considered, but customized population specific approaches are needed to address unique drivers of malnutrition risk. Funding Sources/UNASSIGNED:New York University Center for the Study of Asian American Health Pilot Project Program for Alzheimer's Disease & Thomas J. Long Foundation. Supporting Tables Images and/or Graphs/UNASSIGNED/:
PMCID:6573918
PMID: 31223775
ISSN: 2475-2991
CID: 3939442

A hypothesis linking the energy demand of the brain to obesity risk

Kuzawa, Christopher W; Blair, Clancy
The causes of obesity are complex and multifactorial. We propose that one unconsidered but likely important factor is the energetic demand of brain development, which could constrain energy available for body growth and other functions, including fat deposition. Humans are leanest during early childhood and regain body fat in later childhood. Children reaching this adiposity rebound (AR) early are at risk for adult obesity. In aggregate data, the developing brain consumes a lifetime peak of 66% of resting energy expenditure in the years preceding the AR, and brain energy use is inversely related to body weight gain from infancy until puberty. Building on this finding, we hypothesize that individual variation in childhood brain energy expenditure will help explain variation in the timing of the AR and subsequent obesity risk. The idea that brain energetics constrain fat deposition is consistent with evidence that genes that elevate BMI are expressed in the brain and mediate a trade-off between the size of brain structures and BMI. Variability in energy expended on brain development and function could also help explain widely documented inverse relationships between the BMI and cognitive abilities. We estimate that variability in brain energetics could explain the weight differential separating children at the 50th and 70th BMI-for-age centiles immediately before the AR. Our model proposes a role for brain energetics as a driver of variation within a population's BMI distribution and suggests that educational interventions that boost global brain energy use during childhood could help reduce the burden of obesity.
PMID: 31209026
ISSN: 1091-6490
CID: 3938992

Progressive multiple sclerosis is associated with accelerated inner and outer retinal layer atrophy [Meeting Abstract]

Sotirchos, E S; Caldito, N G; Filippatou, A; Fitzgerald, K C; Murphy, O; Lambe, J; Nguyen, J; Ogbuokiri, E; Crainiceanu, C; Frohman, E; Frohman, T; Balcer, L J; Martinez-Lapiscina, E; Villoslada, P; Petzold, A; Balk, L; Calkwood, J; Havla, J; Albrecht, P; Paul, F; Brandt, A U; Prince, J; Calabresi, P A; Saidha, S
Background: Optical coherence tomography (OCT) studies have shown that retinal nerve fiber layer (RNFL) and ganglion cell + inner plexiform layer (GCIP) thinning are accelerated in multiple sclerosis (MS). Increased inner nuclear layer (INL) thickness has been associated with inflammatory disease activity, but decreased thicknesses of the INL and outer nuclear layer (ONL) have also been identified in a subset of patients with more severe disability. INL atrophy has also been found post-mortem in MS eyes, more frequently in progressive MS (PMS). These data suggest that there exist differences in retinal pathology at various stages of the disease, however these have been incompletely characterized, as the vast majority of OCT studies comparing retinal measures between MS subtypes have been cross-sectional, with small numbers of PMS eyes.
Objective(s): To assess the effects of age and MS subtype on longitudinal changes in retinal layer thicknesses.
Method(s): A cohort of MS patients and healthy controls (HC), followed with serial spectral-domain OCT, was evaluated. Retinal layer thicknesses were derived utilizing a validated, automated segmentation algorithm. Statistical analyses were performed with mixed-effects linear regression models.
Result(s): Data from 364 MS (178 relapsing-remitting MS [RRMS], 186 PMS) and 66 HC participants were analyzed. Median follow-up duration was 3.6 years. Higher age was associated with slower rates of RNFL atrophy in MS (p<0.001), but not in HC. Rates of GCIP atrophy did not differ across age in MS, but in HC higher age was associated with accelerated rates of GCIP atrophy (p=0.006). The proportion of RNFL and GCIP atrophy in MS attributable to normal aging increased from 42.7% and 16.7% respectively at age 25 years, to 83.7% and 81.1% at age 65 years. PMS was independently associated with accelerated RNFL and GCIP atrophy compared to RRMS (RNFL: p=0.002; GCIP: p=0.001). Higher age was associated with accelerated INL and ONL atrophy and this relationship was similar in MS and HC. INL and ONL atrophy rates were faster in PMS compared to HC (INL: p=0.03; ONL: p=0.04) and RRMS (INL: p=0.008; ONL: p=0.01), but did not differ between RRMS and HC.
Conclusion(s): PMS is independently associated with accelerated retinal layer atrophy, and INL and ONL atrophy may be novel biomarkers of neurodegeneration in PMS. The effects of normal aging on retinal layer thicknesses should be considered when designing clinical trials incorporating OCT measures as outcomes
EMBASE:628003737
ISSN: 1477-0970
CID: 3931542

Effects of high myopia on retinal layer rates of change as measured by optical coherence tomography [Meeting Abstract]

Fioravante, N J; Kwakyi, O; Filippatou, A; Cowley, N J; Risher, H; Ogbuokiri, E; Pellegrini, N; Frohman, E; Frohman, T; Balcer, L J; Saidha, S; Calabresi, P A
Background: Myopia's axial elongation of the eye causes an irregularly shaped retina. Cross-sectional studies show that increasing diopters and axial lengths in myopia correlate negatively with Optical Coherence Tomography (OCT) derived measures of Retinal Nerve Fiber Layer (RNFL) thickness. This has largely precluded including OCT data from high myopia individuals in Multiple Sclerosis (MS) and other studies. OCT is a promising marker of neurodegeneration in MS. However, the impact of high myopia in longitudinal studies remains to be investigated.
Objective(s): To assess the impact of high myopia on rates of change in OCT retinal layer thicknesses in MS patients and healthy controls (HC).
Method(s): A 1:2 age and sex matching scheme was used in the MS [13 high myopia (MSHM): 26 non myopia (MSNM)] and HC [7 high myopia (HCHM): 14 non myopia (HCNM)] cohorts. OCT thickness measures of the peripapillary RNFL (pRNFL), ganglion cell+inner plexiform layer (GCIP), and other retinal layers were determined using a validated segmentation algorithm. Mixed effects linear regression was used in statistical analyses.
Result(s): Baseline MSHM eyes had lower GCIP (-4.01 mum, p = 0.06) and pRNFL thicknesses (-8.15 mum, p = 0.04), as compared to MSNM eyes. HC GCIP and pRNFL thicknesses were lower in HCHM than HCNM eyes (-4.15 mum, p = 0.01 and -0.84 mum, p = 0.83 respectively). Despite cross-sectional differences in retinal layer thicknesses in eyes stratified by myopia, longitudinal (median duration of follow-up= 4.6, 6.9, 4.0, 5.1 years in MSHM, MSNM, HCHM, and HCNM respectively) rates of retinal layer change did not differ between participants with and without high myopia. In the MS cohort, rates of thinning were significant in both groups but there was no difference between rates of GCIP and pRNFL thinning among MSHM and MSNM (DELTA0.07 mum/y, p = 0.71 and DELTA0.12 mum/y, p = 0.52 respectively) eyes. Similarly, no difference in rates of GCIP and pRNFL change was found between HCHM and HCNM (DELTA0.06 mum/y, p = 0.49 and DELTA0.21 mum/y, p = 0.22 respectively) eyes. Similar results were observed for the inner and outer nuclear layers in MS and HCs.
Conclusion(s): Although cross-sectional retinal thickness measures may vary due to myopia, longitudinal rates of retinal change appear unaffected. Therefore, despite longstanding opinion, our findings suggest high myopia may not confound longitudinal OCT analyses. Future research is needed to verify and validate our preliminary findings in larger, longitudinal studies
EMBASE:628003357
ISSN: 1477-0970
CID: 3931532

Alterations in the retinal vasculature occur in multiple sclerosis and exhibit novel correlations with disability and visual function measures

Murphy, Olwen C; Kwakyi, Ohemaa; Iftikhar, Mustafa; Zafar, Sidra; Lambe, Jeffrey; Pellegrini, Nicole; Sotirchos, Elias S; Gonzalez-Caldito, Natalia; Ogbuokiri, Esther; Filippatou, Angeliki; Risher, Hunter; Cowley, Norah; Feldman, Sydney; Fioravante, Nicholas; Frohman, Elliot M; Frohman, Teresa C; Balcer, Laura J; Prince, Jerry L; Channa, Roomasa; Calabresi, Peter A; Saidha, Shiv
BACKGROUND/UNASSIGNED:The retinal vasculature may be altered in multiple sclerosis (MS), potentially acting as a biomarker of disease processes. OBJECTIVE/UNASSIGNED:To compare retinal vascular plexus densities in people with MS (PwMS) and healthy controls (HCs), and examine correlations with visual function and global disability. METHODS/UNASSIGNED:In this cross-sectional study, 111 PwMS (201 eyes) and 50 HCs (97 eyes) underwent optical coherence tomography angiography (OCTA). Macular superficial vascular plexus (SVP) and deep vascular plexus (DVP) densities were quantified, and poor quality images were excluded according to an artifact-rating protocol. RESULTS/UNASSIGNED: = 0.31; p < 0.001 for all). CONCLUSIONS/UNASSIGNED:Retinal SVP density measured by OCTA is reduced across MS eyes, and correlates with visual function, EDSS, and MSFC scores.
PMID: 31094280
ISSN: 1477-0970
CID: 3935822

The development of executive function in early childhood is inversely related to change in body mass index: Evidence for an energetic tradeoff?

Blair, Clancy; Kuzawa, Christopher W; Willoughby, Michael T
A well-established literature demonstrates executive function (EF) deficits in obese children and adults relative to healthy weight comparisons. EF deficits in obesity are associated with overeating and impulsive consumption of high calorie foods leading to excess weight gain and to problems with metabolic regulation and low-grade inflammation that detrimentally affect the structure and function of prefrontal cortex. Here, we test a complementary explanation for the relation between EF and body mass index (BMI) grounded in the energy demand of the developing brain. Recent work shows that the brain accounts for a lifetime peak of 66% of resting metabolic rate in childhood and that developmental changes in brain energetics and normative changes in body weight gain are closely inversely related. This finding suggests a trade-off in early childhood between energy used to support brain development versus energy used to support physical growth and fat deposition. To test this theorized energetic trade-off, we analyzed data from a large longitudinal sample (N = 1,292) and found that change in EF from age 3 to 5 years, as a proxy for brain development in energetically costly prefrontal cortex, is inversely related to change in BMI from age 2 to 5 years. Greater linear decline in BMI predicted greater linear increase in EF. We interpret this finding as tentative support for a brain-body energetic trade-off in early childhood with implications for lifetime obesity risk.
PMID: 31102547
ISSN: 1467-7687
CID: 3935872

Early Shared Reading Is Associated with Less Harsh Parenting

Jimenez, Manuel E; Mendelsohn, Alan L; Lin, Yong; Shelton, Patricia; Reichman, Nancy
OBJECTIVE:Shared reading is believed to enhance parent-child relationships, but the extent to which it reduces harsh parenting is understudied. Associations between early shared reading and subsequent harsh parenting were investigated. METHODS:Data from a national urban birth cohort were used to estimate associations between mother-reported shared reading at ages 1 and 3 years and harsh parenting-based on a composite of psychological and physical aggression subscales of a validated self-report instrument-when the children were at ages 3 and 5 years. The authors used multivariable linear regression and generalized estimating equations to account for repeated observations. Given potential inverse associations between shared reading and child disruptive behaviors, which can trigger harsh parenting, the authors investigated the extent to which children's behavior at age 3 years mediated the association between shared reading at age 1 year and harsh parenting at age 5 years. RESULTS:This study included 2165 mother-child dyads. Thirty-four percent and 52% of mothers reported daily reading at ages 1 and 3 years. In adjusted models, shared reading at age 1 year was associated with less harsh parenting at age 3 years. Similarly, shared reading at age 3 years was associated with less harsh parenting at age 5 years. These associations remained significant in lagged repeated-measures models. Decreased disruptive behaviors partially mediated the association between shared reading at age 1 year and harsh parenting at age 5 years. CONCLUSION/CONCLUSIONS:Shared reading predicted less harsh parenting in a national urban sample. These findings suggest that shared reading contributes to an important aspect of the parent-child relationship and that some of the association operates through enhanced child behaviors.
PMID: 31107765
ISSN: 1536-7312
CID: 3935892

A catalog of genetic loci associated with kidney function from analyses of a million individuals

Wuttke, Matthias; Li, Yong; Li, Man; Sieber, Karsten B; Feitosa, Mary F; Gorski, Mathias; Tin, Adrienne; Wang, Lihua; Chu, Audrey Y; Hoppmann, Anselm; Kirsten, Holger; Giri, Ayush; Chai, Jin-Fang; Sveinbjornsson, Gardar; Tayo, Bamidele O; Nutile, Teresa; Fuchsberger, Christian; Marten, Jonathan; Cocca, Massimiliano; Ghasemi, Sahar; Xu, Yizhe; Horn, Katrin; Noce, Damia; van der Most, Peter J; Sedaghat, Sanaz; Yu, Zhi; Akiyama, Masato; Afaq, Saima; Ahluwalia, Tarunveer S; Almgren, Peter; Amin, Najaf; Ärnlöv, Johan; Bakker, Stephan J L; Bansal, Nisha; Baptista, Daniela; Bergmann, Sven; Biggs, Mary L; Biino, Ginevra; Boehnke, Michael; Boerwinkle, Eric; Boissel, Mathilde; Bottinger, Erwin P; Boutin, Thibaud S; Brenner, Hermann; Brumat, Marco; Burkhardt, Ralph; Butterworth, Adam S; Campana, Eric; Campbell, Archie; Campbell, Harry; Canouil, Mickaël; Carroll, Robert J; Catamo, Eulalia; Chambers, John C; Chee, Miao-Ling; Chee, Miao-Li; Chen, Xu; Cheng, Ching-Yu; Cheng, Yurong; Christensen, Kaare; Cifkova, Renata; Ciullo, Marina; Concas, Maria Pina; Cook, James P; Coresh, Josef; Corre, Tanguy; Sala, Cinzia Felicita; Cusi, Daniele; Danesh, John; Daw, E Warwick; de Borst, Martin H; De Grandi, Alessandro; de Mutsert, Renée; de Vries, Aiko P J; Degenhardt, Frauke; Delgado, Graciela; Demirkan, Ayse; Di Angelantonio, Emanuele; Dittrich, Katalin; Divers, Jasmin; Dorajoo, Rajkumar; Eckardt, Kai-Uwe; Ehret, Georg; Elliott, Paul; Endlich, Karlhans; Evans, Michele K; Felix, Janine F; Foo, Valencia Hui Xian; Franco, Oscar H; Franke, Andre; Freedman, Barry I; Freitag-Wolf, Sandra; Friedlander, Yechiel; Froguel, Philippe; Gansevoort, Ron T; Gao, He; Gasparini, Paolo; Gaziano, J Michael; Giedraitis, Vilmantas; Gieger, Christian; Girotto, Giorgia; Giulianini, Franco; Gögele, Martin; Gordon, Scott D; Gudbjartsson, Daniel F; Gudnason, Vilmundur; Haller, Toomas; Hamet, Pavel; Harris, Tamara B; Hartman, Catharina A; Hayward, Caroline; Hellwege, Jacklyn N; Heng, Chew-Kiat; Hicks, Andrew A; Hofer, Edith; Huang, Wei; Hutri-Kähönen, Nina; Hwang, Shih-Jen; Ikram, M Arfan; Indridason, Olafur S; Ingelsson, Erik; Ising, Marcus; Jaddoe, Vincent W V; Jakobsdottir, Johanna; Jonas, Jost B; Joshi, Peter K; Josyula, Navya Shilpa; Jung, Bettina; Kähönen, Mika; Kamatani, Yoichiro; Kammerer, Candace M; Kanai, Masahiro; Kastarinen, Mika; Kerr, Shona M; Khor, Chiea-Chuen; Kiess, Wieland; Kleber, Marcus E; Koenig, Wolfgang; Kooner, Jaspal S; Körner, Antje; Kovacs, Peter; Kraja, Aldi T; Krajcoviechova, Alena; Kramer, Holly; Krämer, Bernhard K; Kronenberg, Florian; Kubo, Michiaki; Kühnel, Brigitte; Kuokkanen, Mikko; Kuusisto, Johanna; La Bianca, Martina; Laakso, Markku; Lange, Leslie A; Langefeld, Carl D; Lee, Jeannette Jen-Mai; Lehne, Benjamin; Lehtimäki, Terho; Lieb, Wolfgang; Lim, Su-Chi; Lind, Lars; Lindgren, Cecilia M; Liu, Jun; Liu, Jianjun; Loeffler, Markus; Loos, Ruth J F; Lucae, Susanne; Lukas, Mary Ann; Lyytikäinen, Leo-Pekka; Mägi, Reedik; Magnusson, Patrik K E; Mahajan, Anubha; Martin, Nicholas G; Martins, Jade; März, Winfried; Mascalzoni, Deborah; Matsuda, Koichi; Meisinger, Christa; Meitinger, Thomas; Melander, Olle; Metspalu, Andres; Mikaelsdottir, Evgenia K; Milaneschi, Yuri; Miliku, Kozeta; Mishra, Pashupati P; Mohlke, Karen L; Mononen, Nina; Montgomery, Grant W; Mook-Kanamori, Dennis O; Mychaleckyj, Josyf C; Nadkarni, Girish N; Nalls, Mike A; Nauck, Matthias; Nikus, Kjell; Ning, Boting; Nolte, Ilja M; Noordam, Raymond; O'Connell, Jeffrey; O'Donoghue, Michelle L; Olafsson, Isleifur; Oldehinkel, Albertine J; Orho-Melander, Marju; Ouwehand, Willem H; Padmanabhan, Sandosh; Palmer, Nicholette D; Palsson, Runolfur; Penninx, Brenda W J H; Perls, Thomas; Perola, Markus; Pirastu, Mario; Pirastu, Nicola; Pistis, Giorgio; Podgornaia, Anna I; Polasek, Ozren; Ponte, Belen; Porteous, David J; Poulain, Tanja; Pramstaller, Peter P; Preuss, Michael H; Prins, Bram P; Province, Michael A; Rabelink, Ton J; Raffield, Laura M; Raitakari, Olli T; Reilly, Dermot F; Rettig, Rainer; Rheinberger, Myriam; Rice, Kenneth M; Ridker, Paul M; Rivadeneira, Fernando; Rizzi, Federica; Roberts, David J; Robino, Antonietta; Rossing, Peter; Rudan, Igor; Rueedi, Rico; Ruggiero, Daniela; Ryan, Kathleen A; Saba, Yasaman; Sabanayagam, Charumathi; Salomaa, Veikko; Salvi, Erika; Saum, Kai-Uwe; Schmidt, Helena; Schmidt, Reinhold; Schöttker, Ben; Schulz, Christina-Alexandra; Schupf, Nicole; Shaffer, Christian M; Shi, Yuan; Smith, Albert V; Smith, Blair H; Soranzo, Nicole; Spracklen, Cassandra N; Strauch, Konstantin; Stringham, Heather M; Stumvoll, Michael; Svensson, Per O; Szymczak, Silke; Tai, E-Shyong; Tajuddin, Salman M; Tan, Nicholas Y Q; Taylor, Kent D; Teren, Andrej; Tham, Yih-Chung; Thiery, Joachim; Thio, Chris H L; Thomsen, Hauke; Thorleifsson, Gudmar; Toniolo, Daniela; Tönjes, Anke; Tremblay, Johanne; Tzoulaki, Ioanna; Uitterlinden, André G; Vaccargiu, Simona; van Dam, Rob M; van der Harst, Pim; van Duijn, Cornelia M; Velez Edward, Digna R; Verweij, Niek; Vogelezang, Suzanne; Völker, Uwe; Vollenweider, Peter; Waeber, Gerard; Waldenberger, Melanie; Wallentin, Lars; Wang, Ya Xing; Wang, Chaolong; Waterworth, Dawn M; Bin Wei, Wen; White, Harvey; Whitfield, John B; Wild, Sarah H; Wilson, James F; Wojczynski, Mary K; Wong, Charlene; Wong, Tien-Yin; Xu, Liang; Yang, Qiong; Yasuda, Masayuki; Yerges-Armstrong, Laura M; Zhang, Weihua; Zonderman, Alan B; Rotter, Jerome I; Bochud, Murielle; Psaty, Bruce M; Vitart, Veronique; Wilson, James G; Dehghan, Abbas; Parsa, Afshin; Chasman, Daniel I; Ho, Kevin; Morris, Andrew P; Devuyst, Olivier; Akilesh, Shreeram; Pendergrass, Sarah A; Sim, Xueling; Böger, Carsten A; Okada, Yukinori; Edwards, Todd L; Snieder, Harold; Stefansson, Kari; Hung, Adriana M; Heid, Iris M; Scholz, Markus; Teumer, Alexander; Köttgen, Anna; Pattaro, Cristian
Chronic kidney disease (CKD) is responsible for a public health burden with multi-systemic complications. Through trans-ancestry meta-analysis of genome-wide association studies of estimated glomerular filtration rate (eGFR) and independent replication (n = 1,046,070), we identified 264 associated loci (166 new). Of these, 147 were likely to be relevant for kidney function on the basis of associations with the alternative kidney function marker blood urea nitrogen (n = 416,178). Pathway and enrichment analyses, including mouse models with renal phenotypes, support the kidney as the main target organ. A genetic risk score for lower eGFR was associated with clinically diagnosed CKD in 452,264 independent individuals. Colocalization analyses of associations with eGFR among 783,978 European-ancestry individuals and gene expression across 46 human tissues, including tubulo-interstitial and glomerular kidney compartments, identified 17 genes differentially expressed in kidney. Fine-mapping highlighted missense driver variants in 11 genes and kidney-specific regulatory variants. These results provide a comprehensive priority list of molecular targets for translational research.
PMID: 31152163
ISSN: 1546-1718
CID: 3936112