@article {1141, title = {Multiple loci influence erythrocyte phenotypes in the CHARGE Consortium.}, journal = {Nat Genet}, volume = {41}, year = {2009}, month = {2009 Nov}, pages = {1191-8}, abstract = {

Measurements of erythrocytes within the blood are important clinical traits and can indicate various hematological disorders. We report here genome-wide association studies (GWAS) for six erythrocyte traits, including hemoglobin concentration (Hb), hematocrit (Hct), mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), mean corpuscular hemoglobin concentration (MCHC) and red blood cell count (RBC). We performed an initial GWAS in cohorts of the CHARGE Consortium totaling 24,167 individuals of European ancestry and replication in additional independent cohorts of the HaemGen Consortium totaling 9,456 individuals. We identified 23 loci significantly associated with these traits in a meta-analysis of the discovery and replication cohorts (combined P values ranging from 5 x 10(-8) to 7 x 10(-86)). Our findings include loci previously associated with these traits (HBS1L-MYB, HFE, TMPRSS6, TFR2, SPTA1) as well as new associations (EPO, TFRC, SH2B3 and 15 other loci). This study has identified new determinants of erythrocyte traits, offering insight into common variants underlying variation in erythrocyte measures.

}, keywords = {Blood Pressure, Cell Line, Cohort Studies, Endothelial Cells, Erythrocytes, Gene Expression, Genome, Human, Genome-Wide Association Study, Humans, Hypertension, Phenotype, Polymorphism, Single Nucleotide, Quantitative Trait Loci}, issn = {1546-1718}, doi = {10.1038/ng.466}, author = {Ganesh, Santhi K and Zakai, Neil A and van Rooij, Frank J A and Soranzo, Nicole and Smith, Albert V and Nalls, Michael A and Chen, Ming-Huei and K{\"o}ttgen, Anna and Glazer, Nicole L and Dehghan, Abbas and Kuhnel, Brigitte and Aspelund, Thor and Yang, Qiong and Tanaka, Toshiko and Jaffe, Andrew and Bis, Joshua C M and Verwoert, Germaine C and Teumer, Alexander and Fox, Caroline S and Guralnik, Jack M and Ehret, Georg B and Rice, Kenneth and Felix, Janine F and Rendon, Augusto and Eiriksdottir, Gudny and Levy, Daniel and Patel, Kushang V and Boerwinkle, Eric and Rotter, Jerome I and Hofman, Albert and Sambrook, Jennifer G and Hernandez, Dena G and Zheng, Gang and Bandinelli, Stefania and Singleton, Andrew B and Coresh, Josef and Lumley, Thomas and Uitterlinden, Andr{\'e} G and Vangils, Janine M and Launer, Lenore J and Cupples, L Adrienne and Oostra, Ben A and Zwaginga, Jaap-Jan and Ouwehand, Willem H and Thein, Swee-Lay and Meisinger, Christa and Deloukas, Panos and Nauck, Matthias and Spector, Tim D and Gieger, Christian and Gudnason, Vilmundur and van Duijn, Cornelia M and Psaty, Bruce M and Ferrucci, Luigi and Chakravarti, Aravinda and Greinacher, Andreas and O{\textquoteright}Donnell, Christopher J and Witteman, Jacqueline C M and Furth, Susan and Cushman, Mary and Harris, Tamara B and Lin, Jing-Ping} } @article {6107, title = {Long-term survival in adults 65 years and older with white matter hyperintensity: association with performance on the digit symbol substitution test.}, journal = {Psychosom Med}, volume = {75}, year = {2013}, month = {2013 Sep}, pages = {624-31}, abstract = {

OBJECTIVE: White matter hyperintensity (WMH) confers increased mortality risk in patients with cardiovascular diseases. However, little is known about differences in survival times among adults 65 years and older who have WMH and live in the community. To characterize the factors that may reduce mortality risk in the presence of WMH, measures of race, sex, apolipoprotein E4, neuroimaging, and cardiometabolic, physiological, and psychosocial characteristics were examined, with a particular focus on information processing as measured by the Digit Symbol Substitution Test (DSST).

METHODS: Cox proportional models were used to estimate mortality risks in a cohort of 3513 adults (74.8 years, 58\% women, 84\% white) with WMH (0-9 points), DSST (0-90 points), risk factor assessment in 1992 to 1994, and data on mortality and incident stroke in 2009 (median follow-up [range] = 14.2 [0.5-18.1] years).

RESULTS: WMH predicted a 48\% greater mortality risk (age-adjusted hazard ratio [HR; 95\% confidence interval {CI}] for WMH >3 points = 1.48 [1.35-1.62]). This association was attenuated after adjustment for DSST (HR [CI] = 1.38 [1.27-1.51]) or lacunar infarcts (HR [CI] = 1.37 [1.25,1.50]) but not after adjustment for other factors. The interaction between DSST and WMH was significant (p = .011). In fully adjusted models stratified by WMH of 3 or higher, participants with DSST greater than or equal to median had a 34\% lower mortality risk among those with WMH of 3 or higher (n = 532/1217) and a 28\% lower mortality risk among those with WMH lower than 3 (n = 1364/2296), compared with participants with DSST less than median (HR [95\% CI] = 0.66 [0.55-0.81] and 0.72 [0.62-0.83], respectively).

CONCLUSIONS: WMH is associated with increased long-term mortality risk in community-dwelling adults 65 years and older. The increased risk is attenuated for those with higher DSST. Assessment of cognitive function with DSST may improve risk stratification of individuals with WMH.

}, keywords = {Aged, Apolipoprotein E4, Biomarkers, Brain, Cardiovascular Diseases, Epidemiologic Methods, Female, Humans, Life Style, Magnetic Resonance Imaging, Male, Neuroimaging, Neuropsychological Tests, Reaction Time, Sex Factors, Stroke, Survivors}, issn = {1534-7796}, doi = {10.1097/PSY.0b013e31829c1df2}, author = {Rosano, Caterina and Chang, Yue-Fang and Kuller, Lewis H and Guralnik, Jack M and Studenski, Stephanie A and Aizenstein, Howard J and Gianaros, Peter J and Lopez, Oscar L and Longstreth, William T and Newman, Anne B} } @article {7161, title = {Gait Speed Predicts Incident Disability: A Pooled Analysis.}, journal = {J Gerontol A Biol Sci Med Sci}, volume = {71}, year = {2016}, month = {2016 Jan}, pages = {63-71}, abstract = {

BACKGROUND: Functional independence with aging is an important goal for individuals and society. Simple prognostic indicators can inform health promotion and care planning, but evidence is limited by heterogeneity in measures of function.

METHODS: We performed a pooled analysis of data from seven studies of 27,220 community-dwelling older adults aged 65 or older with baseline gait speed, followed for disability and mortality. Outcomes were incident inability or dependence on another person in bathing or dressing; and difficulty walking {\textonequarter} - {\textonehalf} mile or climbing 10 steps within 3 years.

RESULTS: Participants with faster baseline gait had lower rates of incident disability. In subgroups (defined by 0.2 m/s-wide intervals from <0.4 to >= 1.4 m/s) with increasingly greater gait speed, 3-year rates of bathing or dressing dependence trended from 10\% to 1\% in men, and from 15\% to 1\% in women, while mobility difficulty trended from 47\% to 4\% in men and 40\% to 6\% in women. The age-adjusted relative risk ratio per 0.1 m/s greater speed for bathing or dressing dependence in men was 0.68 (0.57-0.81) and in women: 0.74 (0.66-0.82); for mobility difficulty, men: 0.75 (0.68-0.82), women: 0.73 (0.67-0.80). Results were similar for combined disability and mortality. Effects were largely consistent across subgroups based on age, gender, race, body mass index, prior hospitalization, and selected chronic conditions. In the presence of multiple other risk factors for disability, gait speed significantly increased the area under the receiver operator characteristic curve.

CONCLUSION: In older adults, gait speed predicts 3 year incidence of bathing or dressing dependence, mobility difficulty, and a composite outcome of disability and mortality.

}, keywords = {Activities of Daily Living, Aged, Aged, 80 and over, Aging, Cohort Studies, Disability Evaluation, Disabled Persons, Female, Gait, Geriatric Assessment, Humans, Independent Living, Male, Mobility Limitation, Predictive Value of Tests, Prognosis, Psychomotor Performance, Risk Assessment, Risk Factors, ROC Curve, Survival Analysis, United States}, issn = {1758-535X}, doi = {10.1093/gerona/glv126}, author = {Perera, Subashan and Patel, Kushang V and Rosano, Caterina and Rubin, Susan M and Satterfield, Suzanne and Harris, Tamara and Ensrud, Kristine and Orwoll, Eric and Lee, Christine G and Chandler, Julie M and Newman, Anne B and Cauley, Jane A and Guralnik, Jack M and Ferrucci, Luigi and Studenski, Stephanie A} }