TY - JOUR T1 - Knowledge of risk among patients at increased risk for stroke. JF - Stroke Y1 - 1997 A1 - Samsa, G P A1 - Cohen, S J A1 - Goldstein, L B A1 - Bonito, A J A1 - Duncan, P W A1 - Enarson, C A1 - DeFriese, G H A1 - Horner, R D A1 - Matchar, D B KW - Adult KW - Aged KW - Aged, 80 and over KW - Awareness KW - Cerebrovascular Disorders KW - Female KW - Humans KW - Knowledge KW - Male KW - Middle Aged KW - Multivariate Analysis KW - Risk Factors AB -

BACKGROUND AND PURPOSE: Patients who recognize their increased risk for stroke are more likely to engage in (and comply with) stroke prevention practices than those who do not. We describe perceived risk of stroke among a nationally diverse sample of patients at increased risk for stroke and determine whether patients' knowledge of their stroke risk varied according to patients' demographic and clinical characteristics.

METHODS: Respondents were recruited from the Academic Medical Center Consortium (n = 621, five academic medical centers, inpatients of varying age); the Cardiovascular Health Study (n = 321, population-based sample of persons aged 65+ years); and United HealthCare (n = 319, five health plans, inpatients and outpatients typically younger than 65 years). The primary outcome was awareness of being at risk for stroke.

RESULTS: Only 41% of respondents were aware of their increased risk for stroke (including less than one half of patients with previous minor stroke). Approximately 74% of patients who recalled being told of their increased stroke risk by a physician acknowledged this risk in comparison with 28% of patients who did not recall being informed by a physician. Younger patients, depressed patients, those in poor current health, and those with a history of TIA were most likely to be aware of their stroke risk.

CONCLUSIONS: Over one half of patients at increased risk of stroke are unaware of their risk. Healthcare providers play a crucial role in communicating information about risk, and successful communication encourages adoption of stroke prevention practices. Educational messages should be targeted toward patients least likely to be aware of their risk.

VL - 28 IS - 5 U1 - http://www.ncbi.nlm.nih.gov/pubmed/9158625?dopt=Abstract ER - TY - JOUR T1 - Kidney function as a predictor of noncardiovascular mortality. JF - J Am Soc Nephrol Y1 - 2005 A1 - Fried, Linda F A1 - Katz, Ronit A1 - Sarnak, Mark J A1 - Shlipak, Michael G A1 - Chaves, Paulo H M A1 - Jenny, Nancy Swords A1 - Stehman-Breen, Catherine A1 - Gillen, Dan A1 - Bleyer, Anthony J A1 - Hirsch, Calvin A1 - Siscovick, David A1 - Newman, Anne B KW - Age Factors KW - Aged KW - Aged, 80 and over KW - Cardiovascular Diseases KW - Cause of Death KW - Cohort Studies KW - Confidence Intervals KW - Creatinine KW - Cystatin C KW - Cystatins KW - Female KW - Glomerular Filtration Rate KW - Humans KW - Kidney Failure, Chronic KW - Kidney Function Tests KW - Longitudinal Studies KW - Male KW - Probability KW - Proportional Hazards Models KW - Risk Assessment KW - Severity of Illness Index KW - Survival Analysis KW - United States AB -

Chronic kidney disease is associated with a higher risk for cardiovascular mortality, as well as all-cause mortality. Whether chronic kidney disease is a predictor of noncardiovascular mortality is less clear. To further explore the latter, the association of kidney function with total noncardiovascular mortality and cause-specific mortality was assessed in the Cardiovascular Health Study, a community-based cohort of older individuals. Kidney disease was assessed using cystatin C and estimated GFR in 4637 participants in 1992 to 1993. Participants were followed until June 30, 2001. Deaths were adjudicated as cardiovascular or noncardiovascular disease by committee, and an underlying cause of death was assigned. The associations of kidney function with total noncardiovascular mortality and cause-specific mortality were analyzed by proportional hazards regression. Noncardiovascular mortality rates increased with higher cystatin C quartiles (16.8, 17.1, 21.6, and 50.0 per 1000 person-years). The association of cystatin C with noncardiovascular mortality persisted after adjustment for demographic factors; the presence of diabetes, C-reactive protein, hemoglobin, and prevalent cardiovascular disease; and measures of atherosclerosis (hazard ratio 1.69; 95% confidence interval 1.33 to 2.15, for the fourth quartile versus the first quartile). Results for estimated GFR were similar. The risk for noncardiac deaths attributed to pulmonary disease, infection, cancer, and other causes was similarly associated with cystatin C levels. Kidney function predicts noncardiovascular mortality from multiple causes in the elderly. Further research is needed to understand the mechanisms and evaluate interventions to reduce the high mortality rate in chronic kidney disease.

VL - 16 IS - 12 U1 - https://www.ncbi.nlm.nih.gov/pubmed/16251239?dopt=Abstract ER - TY - JOUR T1 - Kidney function predicts the rate of bone loss in older individuals: the Cardiovascular Health Study. JF - J Gerontol A Biol Sci Med Sci Y1 - 2006 A1 - Fried, Linda F A1 - Shlipak, Michael G A1 - Stehman-Breen, Catherine A1 - Mittalhenkle, Anuja A1 - Seliger, Stephen A1 - Sarnak, Mark A1 - Robbins, John A1 - Siscovick, David A1 - Harris, Tamara B A1 - Newman, Anne B A1 - Cauley, Jane A KW - Absorptiometry, Photon KW - Aged KW - Bone Density KW - Creatinine KW - Cystatin C KW - Cystatins KW - Female KW - Hip KW - Humans KW - Kidney Diseases KW - Kidney Function Tests KW - Linear Models KW - Longitudinal Studies KW - Male KW - Osteoporosis KW - Predictive Value of Tests AB -

BACKGROUND: Results of cross-sectional analyses of the association of kidney function with bone mineral density (BMD) have been conflicting. We examined the association of cystatin-C, a new marker of kidney function that is unrelated to lean mass, with initial and follow-up BMD, in an ancillary study of the Cardiovascular Health Study, a population-based cohort of individuals > or = 65 years old.

METHODS: Two years after measurement of cystatin-C and other covariates, the first BMD was measured in Pittsburgh, Pennsylvania and Davis, California, by using dual energy x-ray absorptiometry. Follow-up BMD was measured in Pittsburgh 4 years later. Associations of cystatin-C with initial BMD and the change in BMD (%/y) at the hip were examined with linear regression. Analyses were conducted separately for men and women.

RESULTS: In 1519 participants who had cystatin-C and initial BMD assessed, 614 had follow-up BMD. The percent annual change in BMD at the total hip by cystatin-C quartiles was -0.24, -0.13, -0.40, and -0.66%/y (first to fourth quartile) in women and -0.02, -0.30, -0.18, and -0.94%/y in men. After adjusting for potential confounders, cystatin-C was marginally associated with initial BMD in men but not women. Cystatin-C was associated with bone loss in men; after adjustment for weight loss, cystatin-C was not associated with bone loss in women.

CONCLUSION: Kidney dysfunction, as assessed by cystatin-C, is associated with a more rapid loss of BMD at the hip, especially in men. Further studies are needed to confirm these findings and to determine whether this loss leads to an elevated risk of fracture.

VL - 61 IS - 7 U1 - https://www.ncbi.nlm.nih.gov/pubmed/16870638?dopt=Abstract ER - TY - JOUR T1 - Kidney function, electrocardiographic findings, and cardiovascular events among older adults. JF - Clin J Am Soc Nephrol Y1 - 2007 A1 - Kestenbaum, Bryan A1 - Rudser, Kyle D A1 - Shlipak, Michael G A1 - Fried, Linda F A1 - Newman, Anne B A1 - Katz, Ronit A1 - Sarnak, Mark J A1 - Seliger, Stephen A1 - Stehman-Breen, Catherine A1 - Prineas, Ronald A1 - Siscovick, David S KW - Aged KW - Aged, 80 and over KW - Cardiac Output, Low KW - Cardiovascular Diseases KW - Chronic Disease KW - Coronary Disease KW - Electrocardiography KW - Female KW - Humans KW - Kidney KW - Kidney Diseases KW - Male KW - Risk Assessment AB -

Chronic kidney disease (CKD) is associated with cardiovascular (CV) disease and mortality. It is not known whether cardiac rhythm disturbances are more prevalent among individuals with CKD or whether resting electrocardiogram findings predict future CV events in the CKD setting. Data were obtained from the Cardiovascular Health Study, a community-based study of adults aged >/=65 yr. After exclusions for prevalent heart disease, atrial fibrillation, implantable pacemaker, or antiarrhythmic medication use, 3238 participants were analyzed. CKD was defined by an estimated GFR <60 ml/min per 1.73 m(2). Outcomes were adjudicated incident heart failure (HF), incident coronary heart disease (CHD), and mortality. Participants with CKD had longer PR and corrected QT intervals compared with those without CKD; however, differences in electrocardiographic markers were explained by traditional CV risk factors and CV medication use. After adjustment for known risk factors, each 10-ms increase in the QRS interval was associated with a 15% greater risk for incident HF (95% confidence interval [CI] 1.04 to 1.27), a 13% greater risk for CHD (95% CI 1.04 to 1.24), and a 17% greater risk for mortality (95% CI 1.09, 1.25) among CKD participants. Each 5% increase in QTI was associated with a 42% (95% CI 1.23 to 1.65), 22% (95% CI 1.07 to 1.40), and 10% (95% CI 0.98 to 1.22) greater risk for HF, CHD, and mortality, respectively. Associations seemed stronger for participants with CKD; however, no significant interactions were detected. Resting electrocardiographic abnormalities are common in CKD and independently predict future clinical CV events in this setting.

VL - 2 IS - 3 U1 - https://www.ncbi.nlm.nih.gov/pubmed/17699457?dopt=Abstract ER - TY - JOUR T1 - Knee height and arm span: a reflection of early life environment and risk of dementia. JF - Neurology Y1 - 2008 A1 - Huang, T L A1 - Carlson, M C A1 - Fitzpatrick, A L A1 - Kuller, L H A1 - Fried, L P A1 - Zandi, P P KW - Aged KW - Aged, 80 and over KW - Aging KW - Anthropometry KW - Arm KW - Body Height KW - Brain KW - Child KW - Child, Preschool KW - Dementia KW - Environment KW - Female KW - Follow-Up Studies KW - Humans KW - Infant KW - Infant, Newborn KW - Knee KW - Male KW - Middle Aged KW - Prospective Studies KW - Risk Factors KW - Sex Characteristics KW - Skeleton AB -

OBJECTIVES: To determine if anthropometric measures, as markers of early life environment, are associated with risk of dementia, Alzheimer disease (AD), and vascular dementia (VaD).

METHODS: A total of 2,798 subjects were followed as part of the Cardiovascular Health Cognition Study for an average of 5.4 years; 480 developed dementia. Knee height was measured 3 years prior to and arm span 4 years after the study's baseline. Cox proportional hazard models were used to examine their association with subsequent risk of dementia, AD, and VaD.

RESULTS: Among women, greater knee height and arm span were associated with lower risks of dementia (knee height: HR per 1-inch increase 0.84; 95% CI 0.74-0.96; arm span: HR per 1-inch increase 0.93; 95% CI 0.88-0.98) and AD (knee height: HR per 1-inch increase 0.78; 95% CI 0.65-0.93; arm span: HR per 1-inch increase 0.90; 95% CI 0.85-0.96). Women in the lowest quartile of arm span had approximately 1.5 times greater risk of dementia (HR 1.45; 95% CI 1.03-2.05) and AD (HR 1.70; 95% CI 1.10-2.62) than other women. Among men, only arm span was associated with lower risks of dementia (HR per 1-inch increase 0.94; 95% CI 0.89-1.00) and AD (HR per 1-inch increase 0.92; 95% CI 0.84-1.00). For each gender, knee height was not associated with VaD, while arm span was associated with a nonsignificant lower risk of VaD.

CONCLUSIONS: Our findings with knee height and arm span are consistent with previous reports and suggest early life environment may play an important role in the determination of future dementia risk.

VL - 70 IS - 19 Pt 2 U1 - https://www.ncbi.nlm.nih.gov/pubmed/18458216?dopt=Abstract ER - TY - JOUR T1 - Kidney function decline in the elderly: impact of lipoprotein-associated phospholipase A(2). JF - Am J Nephrol Y1 - 2011 A1 - Peralta, Carmen A A1 - Katz, Ronit A1 - Shlipak, Michael A1 - Dubin, Ruth A1 - DeBoer, Ian A1 - Jenny, Nancy A1 - Fitzpatrick, Annette A1 - Koro, Carol A1 - Kestenbaum, Bryan A1 - Ix, Joachim A1 - Sarnak, Mark A1 - Cushman, Mary KW - Aged KW - Cardiovascular Diseases KW - Creatinine KW - Cystatin C KW - Disease Progression KW - Female KW - Geriatrics KW - Glomerular Filtration Rate KW - Humans KW - Kidney KW - Kidney Diseases KW - Male KW - Middle Aged KW - Phospholipases A2 KW - Risk Factors KW - Treatment Outcome AB -

BACKGROUND: Whether lipoprotein-associated phospholipase A(2) (Lp-PLA(2)) levels are associated with kidney function decline has not been well studied.

METHODS: We investigated associations of Lp-PLA(2) antigen and activity with kidney function decline and rapid decline over 5.7 years in the Cardiovascular Health Study (n = 4,359). We estimated kidney function by cystatin C (eGFRcys) in repeated measures, and defined rapid decline as ≥3 ml/min/1.73 m(2) per year. We stratified by baseline preserved GFR (≥60 ml/min/1.73 m(2)).

RESULTS: Mean age was 72 ± 5 years. Average eGFRcys decline was -1.79 ml/min/1.73 m(2) (SD = 2.60) per year. Among persons with preserved GFR, compared to the lowest quartile of Lp-PLA(2) antigen, eGFRcys decline was faster among persons in the second, β -0.31 (95% CI -0.52, -0.10), third -0.19 (-0.41, 0.02) and fourth quartiles -0.26 (-0.48, -0.04) after full adjustment. Persons in the highest quartile of Lp-PLA(2) antigen had increased odds of rapid decline 1.34 (1.03, 1.75), compared to the lowest. There was no significant association between levels of Lp-PLA(2) activity and eGFRcys decline or rapid decline. Associations were not statistically significant among persons with low eGFR (<60 ml/min/1.73 m(2)) at baseline.

CONCLUSION: Higher levels of Lp-PLA(2) antigen but not activity were significantly associated with faster rates of kidney function decline. These findings may suggest a novel vascular pathway for kidney disease progression.

VL - 34 IS - 6 U1 - http://www.ncbi.nlm.nih.gov/pubmed/22056971?dopt=Abstract ER - TY - JOUR T1 - Kidney function and mortality in octogenarians: Cardiovascular Health Study All Stars. JF - J Am Geriatr Soc Y1 - 2012 A1 - Shastri, Shani A1 - Katz, Ronit A1 - Rifkin, Dena E A1 - Fried, Linda F A1 - Odden, Michelle C A1 - Peralta, Carmen A A1 - Chonchol, Michel A1 - Siscovick, David A1 - Shlipak, Michael G A1 - Newman, Anne B A1 - Sarnak, Mark J KW - Aged, 80 and over KW - Analysis of Variance KW - Cardiovascular Diseases KW - Chi-Square Distribution KW - Creatinine KW - Cystatin C KW - Diabetes Mellitus KW - Female KW - Glomerular Filtration Rate KW - Humans KW - Hypertension KW - Kidney Diseases KW - Male KW - Prevalence KW - Proportional Hazards Models KW - Retrospective Studies KW - Risk Factors KW - United States AB -

OBJECTIVES: To examine the association between kidney function and all-cause mortality in octogenarians.

DESIGN: Retrospective analysis of prospectively collected data.

SETTING: Community.

PARTICIPANTS: Serum creatinine and cystatin C were measured in 1,053 Cardiovascular Health Study (CHS) All Stars participants.

MEASUREMENTS: Estimated glomerular filtration rate (eGFR) was determined using the Chronic Kidney Disease Epidemiology Collaboration creatinine (eGFR(CR) ) and cystatin C one-variable (eGFR(CYS) ) equations. The association between quintiles of kidney function and all-cause mortality was analyzed using unadjusted and adjusted Cox proportional hazards models.

RESULTS: Mean age of the participants was 85, 64% were female, 66% had hypertension, 14% had diabetes mellitus, and 39% had prevalent cardiovascular disease. There were 154 deaths over a median follow-up of 2.6 years. The association between eGFR(CR) and all-cause mortality was U-shaped. In comparison with the reference quintile (64-75 mL/min per 1.73 m(2) ), the highest (≥ 75 mL/min per 1.73 m(2) ) and lowest (≤ 43 mL/min per 1.73 m(2) ) quintiles of eGFR(CR) were independently associated with mortality (hazard ratio (HR) = 2.49, 95% confidence interval (CI) = 1.36-4.55; HR = 2.28, 95% CI = 1.26-4.10, respectively). The association between eGFR(CYS) and all-cause mortality was linear in those with eGFR(CYS) of less than 60 mL/min per 1.73 m(2) , and in the multivariate analyses, the lowest quintile of eGFR(CYS) (<52 mL/min per 1.73 m(2) ) was significantly associated with mortality (HR = 2.04, 95% CI = 1.12-3.71) compared with the highest quintile (>0.88 mL/min per 1.73 m(2) ).

CONCLUSION: Moderate reduction in kidney function is a risk factor for all-cause mortality in octogenarians. The association between eGFR(CR) and all-cause mortality differed from that observed with eGFR(CYS) ; the relationship was U-shaped for eGFR(CR) , whereas the risk was primarily present in the lowest quintile for eGFR(CYS) .

VL - 60 IS - 7 U1 - http://www.ncbi.nlm.nih.gov/pubmed/22724391?dopt=Abstract ER - TY - JOUR T1 - Kidney function and prevalent and incident frailty. JF - Clin J Am Soc Nephrol Y1 - 2013 A1 - Dalrymple, Lorien S A1 - Katz, Ronit A1 - Rifkin, Dena E A1 - Siscovick, David A1 - Newman, Anne B A1 - Fried, Linda F A1 - Sarnak, Mark J A1 - Odden, Michelle C A1 - Shlipak, Michael G KW - Age Factors KW - Aged KW - Aged, 80 and over KW - Aging KW - Biomarkers KW - Creatinine KW - Cross-Sectional Studies KW - Cystatin C KW - Fatigue KW - Female KW - Frail Elderly KW - Geriatric Assessment KW - Glomerular Filtration Rate KW - Humans KW - Incidence KW - Independent Living KW - Kidney KW - Kidney Diseases KW - Logistic Models KW - Male KW - Motor Activity KW - Multivariate Analysis KW - Muscle Weakness KW - Odds Ratio KW - Phenotype KW - Prevalence KW - Prospective Studies KW - Risk Factors KW - Time Factors KW - United States KW - Weight Loss AB -

BACKGROUND AND OBJECTIVES: Kidney disease is associated with physiologic changes that may predispose to frailty. This study sought to investigate whether lower levels of kidney function were associated with prevalent or incident frailty in Cardiovascular Health Study (CHS) participants.

DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: CHS enrolled community-dwelling adults age ≥65 years between 1989-1990 and 1992-1993. To examine prevalent frailty, included were 4150 participants without stroke, Parkinson disease, prescribed medications for Alzheimer disease or depression, or severely impaired cognition. To examine incident frailty, included were a subset of 3459 participants without baseline frailty or development of exclusion criteria during follow-up. The primary predictor was estimated GFR (eGFR) calculated using serum cystatin C (eGFR(cys)). Secondary analyses examined eGFR using serum creatinine (eGFR(SCr)). Outcomes were prevalent frailty and incident frailty at 4 years of follow-up. Frailty was ascertained on the basis of weight loss, exhaustion, weakness, slowness, and low physical activity.

RESULTS: The mean age was 75 years and the median eGFR(cys) was 73 ml/min per 1.73 m(2). Among participants with an eGFR(cys) <45 ml/min per 1.73 m(2), 24% had prevalent frailty. In multivariable analysis and compared with eGFR(cys) ≥90 ml/min per 1.73 m(2), eGFR(cys) categories of 45-59 (odds ratio [OR], 1.80; 95% confidence interval [CI], 1.17 to 2.75) and 15-44 (OR, 2.87; 95% CI, 1.72 to 4.77) were associated with higher odds of frailty, whereas 60-75 (OR, 1.14; 95% CI, 0.76 to 1.70) was not. In multivariable analysis, eGFR(cys) categories of 60-75 (incidence rate ratio [IRR], 1.72; 95% CI, 1.07 to 2.75) and 15-44 (IRR, 2.28; 95% CI, 1.23 to 4.22) were associated with higher incidence of frailty whereas 45-59 (IRR, 1.53; 95% CI, 0.90 to 2.60) was not. Lower levels of eGFR(SCr) were not associated with higher risk of prevalent or incident frailty.

CONCLUSIONS: In community-dwelling elders, lower eGFR(cys) was associated with a higher risk of prevalent and incident frailty whereas lower eGFR(SCr) was not. These findings highlight the importance of considering non-GFR determinants of kidney function.

VL - 8 IS - 12 U1 - http://www.ncbi.nlm.nih.gov/pubmed/24178972?dopt=Abstract ER - TY - JOUR T1 - Kidney function and cognitive health in older adults: the Cardiovascular Health Study. JF - Am J Epidemiol Y1 - 2014 A1 - Darsie, Brendan A1 - Shlipak, Michael G A1 - Sarnak, Mark J A1 - Katz, Ronit A1 - Fitzpatrick, Annette L A1 - Odden, Michelle C KW - Aged KW - Cardiovascular Diseases KW - Cognition KW - Cognition Disorders KW - Cystatin C KW - Female KW - Glomerular Filtration Rate KW - Health Status KW - Humans KW - Kidney KW - Kidney Diseases KW - Male KW - Neuropsychological Tests AB -

Recent evidence has demonstrated the importance of kidney function in healthy aging. We examined the association between kidney function and change in cognitive function in 3,907 participants in the Cardiovascular Health Study who were recruited from 4 US communities and studied from 1992 to 1999. Kidney function was measured by cystatin C-based estimated glomerular filtration rate (eGFRcys). Cognitive function was assessed using the Modified Mini-Mental State Examination and the Digit Symbol Substitution Test, which were administered up to 7 times during annual visits. There was an association between eGFRcys and change in cognitive function after adjustment for confounders; persons with an eGFRcys of less than 60 mL/minute/1.73 m(2) had a 0.64 (95% confidence interval: 0.51, 0.77) points/year faster decline in Modified Mini-Mental State Examination score and a 0.42 (95% confidence interval: 0.28, 0.56) points/year faster decline in Digit Symbol Substitution Test score compared with persons with an eGFRcys of 90 or more mL/minute/1.73 m(2). Additional adjustment for intermediate cardiovascular events modestly affected these associations. Participants with an eGFRcys of less than 60 mL/minute/1.73 m(2) had fewer cognitive impairment-free life-years on average compared with those with eGFRcys of 90 or more mL/minute/1.73 m(2), independent of confounders and mediating cardiovascular events (mean difference = -0.44, 95% confidence interval: -0.62, -0.26). Older adults with lower kidney function are at higher risk of worsening cognitive function.

VL - 180 IS - 1 U1 - http://www.ncbi.nlm.nih.gov/pubmed/24844846?dopt=Abstract ER - TY - JOUR T1 - KLB is associated with alcohol drinking, and its gene product β-Klotho is necessary for FGF21 regulation of alcohol preference. JF - Proc Natl Acad Sci U S A Y1 - 2016 A1 - Schumann, Gunter A1 - Liu, Chunyu A1 - O'Reilly, Paul A1 - Gao, He A1 - Song, Parkyong A1 - Xu, Bing A1 - Ruggeri, Barbara A1 - Amin, Najaf A1 - Jia, Tianye A1 - Preis, Sarah A1 - Segura Lepe, Marcelo A1 - Akira, Shizuo A1 - Barbieri, Caterina A1 - Baumeister, Sebastian A1 - Cauchi, Stephane A1 - Clarke, Toni-Kim A1 - Enroth, Stefan A1 - Fischer, Krista A1 - Hällfors, Jenni A1 - Harris, Sarah E A1 - Hieber, Saskia A1 - Hofer, Edith A1 - Hottenga, Jouke-Jan A1 - Johansson, Asa A1 - Joshi, Peter K A1 - Kaartinen, Niina A1 - Laitinen, Jaana A1 - Lemaitre, Rozenn A1 - Loukola, Anu A1 - Luan, Jian'an A1 - Lyytikäinen, Leo-Pekka A1 - Mangino, Massimo A1 - Manichaikul, Ani A1 - Mbarek, Hamdi A1 - Milaneschi, Yuri A1 - Moayyeri, Alireza A1 - Mukamal, Kenneth A1 - Nelson, Christopher A1 - Nettleton, Jennifer A1 - Partinen, Eemil A1 - Rawal, Rajesh A1 - Robino, Antonietta A1 - Rose, Lynda A1 - Sala, Cinzia A1 - Satoh, Takashi A1 - Schmidt, Reinhold A1 - Schraut, Katharina A1 - Scott, Robert A1 - Smith, Albert Vernon A1 - Starr, John M A1 - Teumer, Alexander A1 - Trompet, Stella A1 - Uitterlinden, André G A1 - Venturini, Cristina A1 - Vergnaud, Anne-Claire A1 - Verweij, Niek A1 - Vitart, Veronique A1 - Vuckovic, Dragana A1 - Wedenoja, Juho A1 - Yengo, Loic A1 - Yu, Bing A1 - Zhang, Weihua A1 - Zhao, Jing Hua A1 - Boomsma, Dorret I A1 - Chambers, John A1 - Chasman, Daniel I A1 - Daniela, Toniolo A1 - de Geus, Eco A1 - Deary, Ian A1 - Eriksson, Johan G A1 - Esko, Tõnu A1 - Eulenburg, Volker A1 - Franco, Oscar H A1 - Froguel, Philippe A1 - Gieger, Christian A1 - Grabe, Hans J A1 - Gudnason, Vilmundur A1 - Gyllensten, Ulf A1 - Harris, Tamara B A1 - Hartikainen, Anna-Liisa A1 - Heath, Andrew C A1 - Hocking, Lynne A1 - Hofman, Albert A1 - Huth, Cornelia A1 - Jarvelin, Marjo-Riitta A1 - Jukema, J Wouter A1 - Kaprio, Jaakko A1 - Kooner, Jaspal S A1 - Kutalik, Zoltán A1 - Lahti, Jari A1 - Langenberg, Claudia A1 - Lehtimäki, Terho A1 - Liu, Yongmei A1 - Madden, Pamela A F A1 - Martin, Nicholas A1 - Morrison, Alanna A1 - Penninx, Brenda A1 - Pirastu, Nicola A1 - Psaty, Bruce A1 - Raitakari, Olli A1 - Ridker, Paul A1 - Rose, Richard A1 - Rotter, Jerome I A1 - Samani, Nilesh J A1 - Schmidt, Helena A1 - Spector, Tim D A1 - Stott, David A1 - Strachan, David A1 - Tzoulaki, Ioanna A1 - van der Harst, Pim A1 - van Duijn, Cornelia M A1 - Marques-Vidal, Pedro A1 - Vollenweider, Peter A1 - Wareham, Nicholas J A1 - Whitfield, John B A1 - Wilson, James A1 - Wolffenbuttel, Bruce A1 - Bakalkin, Georgy A1 - Evangelou, Evangelos A1 - Liu, Yun A1 - Rice, Kenneth M A1 - Desrivières, Sylvane A1 - Kliewer, Steven A A1 - Mangelsdorf, David J A1 - Müller, Christian P A1 - Levy, Daniel A1 - Elliott, Paul AB -

Excessive alcohol consumption is a major public health problem worldwide. Although drinking habits are known to be inherited, few genes have been identified that are robustly linked to alcohol drinking. We conducted a genome-wide association metaanalysis and replication study among >105,000 individuals of European ancestry and identified β-Klotho (KLB) as a locus associated with alcohol consumption (rs11940694; P = 9.2 × 10(-12)). β-Klotho is an obligate coreceptor for the hormone FGF21, which is secreted from the liver and implicated in macronutrient preference in humans. We show that brain-specific β-Klotho KO mice have an increased alcohol preference and that FGF21 inhibits alcohol drinking by acting on the brain. These data suggest that a liver-brain endocrine axis may play an important role in the regulation of alcohol drinking behavior and provide a unique pharmacologic target for reducing alcohol consumption.

VL - 113 IS - 50 ER -