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1. Correction: Single-trait and multi-trait genome-wide association analyses identify novel loci for blood pressure in African-ancestry populations.

Author

Liang, J, Le, TH, Velez Edwards, DR, Tayo, BO, Gaulton, KJ, Smith, JA, Lu, Y, Jensen, RA, Chen, G, Yanek, LR, Schwander, K, Tajuddin, SM, Sofer, T, Kim, W, Kayima, J, McKenzie, CA, Fox, E, Nalls, MA, Young, JH, Sun, YV, Lane, JM, Cechova, S, Zhou, J, Tang, H, Fornage, M, Musani, SK, Wang, H, Lee, J, Adeyemo, A, Dreisbach, AW, Forrester, T, Chu, P-L, Cappola, A, Evans, MK, Morrison, AC, Martin, LW, Wiggins, KL, Hui, Q, Zhao, W, Jackson, RD, Ware, EB, Faul, JD, Reiner, AP, Bray, M, Denny, JC, Mosley, TH, Palmas, W, Guo, X, Papanicolaou, GJ, Penman, AD, Polak, JF, Rice, K, Taylor, KD, Boerwinkle, E, Bottinger, EP, Liu, K, Risch, N, Hunt, SC, Kooperberg, C, Zonderman, AB, Laurie, CC, Becker, DM, Cai, J, Loos, RJF, Psaty, BM, Weir, DR, Kardia, SLR, Arnett, DK, Won, S, Edwards, TL, Redline, S, Cooper, RS, Rao, DC, Rotter, JI, Rotimi, C, Levy, D, Chakravarti, A, Zhu, X, and Franceschini, N

Abstract

[This corrects the article DOI: 10.1371/journal.pgen.1006728.].

Published
2018

2. Apolipoprotein L1, income and early kidney damage

Author

Peralta, Carmen, Tamrat, R, Tajuddin, SM, Evans, MK, Zonderman, AB, and Crews, DC

Abstract

© 2015 Tamrat et al.; licensee BioMed Central.Background: The degree to which genetic or environmental factors are associated with early kidney damage among African Americans (AAs) is unknown. Methods: Among 462 AAs in the Healthy Aging in Neighborhoods of

Published
2015

3. Common genetic variation near the connexin-43 gene is associated with resting heart rate in African Americans: A genome-wide association study of 13,372 participants

Author

Deo, R, Nalls, MA, Avery, CL, Smith, JG, Evans, DS, Keller, MF, Butler, AM, Buxbaum, SG, Li, G, Quibrera, P Miguel, Smith, EN, Tanaka, T, Akylbekova, EL, Alonso, A, Arking, DE, Benjamin, EJ, Berenson, GS, Bis, JC, Chen, LY, Chen, W, Cummings, SR, Ellinor, PT, Evans, MK, Ferrucci, L, Fox, ER, Heckbert, SR, Heiss, G, Hsueh, WC, Kerr, KF, Limacher, MC, Liu, Y, Lubitz, SA, Magnani, JW, Mehra, R, Marcus, GM, Murray, SS, Newman, AB, Njajou, O, North, KE, Paltoo, DN, Psaty, BM, Redline, SS, Reiner, AP, Robinson, JG, Rotter, JI, Samdarshi, TE, Schnabel, RB, Schork, NJ, Singleton, AB, Siscovick, D, Soliman, EZ, Sotoodehnia, N, Srinivasan, SR, Taylor, HA, Trevisan, M, Zhang, Z, Zonderman, AB, Newton-Cheh, C, and Whitsel, EA

Subjects
Biomedical and Clinical Sciences, Cardiovascular Medicine and Haematology, Heart Disease, Cardiovascular, Human Genome, Genetics, Clinical Research, Aetiology, 2.1 Biological and endogenous factors, Adult, Black or African American, Aged, Arrhythmias, Cardiac, Connexin 43, Electrocardiography, Female, Genetic Variation, Genome-Wide Association Study, Genotype, Heart Rate, Humans, Male, Meta-Analysis as Topic, Middle Aged, Polymorphism, Single Nucleotide, Rest, United States, African Americans, Heart rate, Singe nucleotide polymorphisms, Meta-analysis, Biomedical Engineering, Cardiorespiratory Medicine and Haematology, Cardiovascular System & Hematology, Cardiovascular medicine and haematology
Abstract

BackgroundGenome-wide association studies have identified several genetic loci associated with variation in resting heart rate in European and Asian populations. No study has evaluated genetic variants associated with heart rate in African Americans.ObjectiveTo identify novel genetic variants associated with resting heart rate in African Americans.MethodsTen cohort studies participating in the Candidate-gene Association Resource and Continental Origins and Genetic Epidemiology Network consortia performed genome-wide genotyping of single nucleotide polymorphisms (SNPs) and imputed 2,954,965 SNPs using HapMap YRI and CEU panels in 13,372 participants of African ancestry. Each study measured the RR interval (ms) from 10-second resting 12-lead electrocardiograms and estimated RR-SNP associations using covariate-adjusted linear regression. Random-effects meta-analysis was used to combine cohort-specific measures of association and identify genome-wide significant loci (P≤2.5×10(-8)).ResultsFourteen SNPs on chromosome 6q22 exceeded the genome-wide significance threshold. The most significant association was for rs9320841 (+13 ms per minor allele; P = 4.98×10(-15)). This SNP was approximately 350 kb downstream of GJA1, a locus previously identified as harboring SNPs associated with heart rate in Europeans. Adjustment for rs9320841 also attenuated the association between the remaining 13 SNPs in this region and heart rate. In addition, SNPs in MYH6, which have been identified in European genome-wide association study, were associated with similar changes in the resting heart rate as this population of African Americans.ConclusionsAn intergenic region downstream of GJA1 (the gene encoding connexin 43, the major protein of the human myocardial gap junction) and an intragenic region within MYH6 are associated with variation in resting heart rate in African Americans as well as in populations of European and Asian origin.

Published
2013

4. Genome-wide meta-analyses of smoking behaviors in African Americans.

Author

David, SP, Hamidovic, A, Chen, GK, Bergen, AW, Wessel, J, Kasberger, JL, Brown, WM, Petruzella, S, Thacker, EL, Kim, Y, Nalls, MA, Tranah, GJ, Sung, YJ, Ambrosone, CB, Arnett, D, Bandera, EV, Becker, DM, Becker, L, Berndt, SI, Bernstein, L, Blot, WJ, Broeckel, U, Buxbaum, SG, Caporaso, N, Casey, G, Chanock, SJ, Deming, SL, Diver, WR, Eaton, CB, Evans, DS, Evans, MK, Fornage, M, Franceschini, N, Harris, TB, Henderson, BE, Hernandez, DG, Hitsman, B, Hu, JJ, Hunt, SC, Ingles, SA, John, EM, Kittles, R, Kolb, S, Kolonel, LN, Le Marchand, L, Liu, Y, Lohman, KK, McKnight, B, Millikan, RC, Murphy, A, Neslund-Dudas, C, Nyante, S, Press, M, Psaty, BM, Rao, DC, Redline, S, Rodriguez-Gil, JL, Rybicki, BA, Signorello, LB, Singleton, AB, Smoller, J, Snively, B, Spring, B, Stanford, JL, Strom, SS, Swan, GE, Taylor, KD, Thun, MJ, Wilson, AF, Witte, JS, Yamamura, Y, Yanek, LR, Yu, K, Zheng, W, Ziegler, RG, Zonderman, AB, Jorgenson, E, Haiman, CA, and Furberg, H

Subjects
Chromosomes, Human, Pair 10, Chromosomes, Human, Pair 15, Humans, Genetic Predisposition to Disease, Proteoglycans, Receptors, Nicotinic, Nerve Tissue Proteins, Smoking, Genotype, Phenotype, Polymorphism, Single Nucleotide, Adult, Aged, Middle Aged, African Americans, Female, Male, Statistics as Topic, Genetic Variation, Genome-Wide Association Study, Genetic Loci, African American, genome-wide association, health disparities, nicotine, smoking, tobacco, Chromosomes, Human, Pair 10, Pair 15, Polymorphism, Single Nucleotide, Receptors, Nicotinic, Clinical Sciences, Public Health and Health Services, Psychology
Abstract

The identification and exploration of genetic loci that influence smoking behaviors have been conducted primarily in populations of the European ancestry. Here we report results of the first genome-wide association study meta-analysis of smoking behavior in African Americans in the Study of Tobacco in Minority Populations Genetics Consortium (n = 32,389). We identified one non-coding single-nucleotide polymorphism (SNP; rs2036527[A]) on chromosome 15q25.1 associated with smoking quantity (cigarettes per day), which exceeded genome-wide significance (β = 0.040, s.e. = 0.007, P = 1.84 × 10(-8)). This variant is present in the 5'-distal enhancer region of the CHRNA5 gene and defines the primary index signal reported in studies of the European ancestry. No other SNP reached genome-wide significance for smoking initiation (SI, ever vs never smoking), age of SI, or smoking cessation (SC, former vs current smoking). Informative associations that approached genome-wide significance included three modestly correlated variants, at 15q25.1 within PSMA4, CHRNA5 and CHRNA3 for smoking quantity, which are associated with a second signal previously reported in studies in European ancestry populations, and a signal represented by three SNPs in the SPOCK2 gene on chr10q22.1. The association at 15q25.1 confirms this region as an important susceptibility locus for smoking quantity in men and women of African ancestry. Larger studies will be needed to validate the suggestive loci that did not reach genome-wide significance and further elucidate the contribution of genetic variation to disparities in cigarette consumption, SC and smoking-attributable disease between African Americans and European Americans.

Published
2012

5. No advantage of A&bgr;42-lowering NSAIDs for prevention of Alzheimer dementia in six pooled cohort studiesSYMBOLSYMBOL

Author

Szekely, CA, Green, RC, Breitner, JCS, Østbye, T, Beiser, AS, Corrada, MM, Dodge, HH, Ganguli, M, Kawas, CH, Kuller, LH, Psaty, BM, Resnick, SM, Wolf, PA, Zonderman, AB, Welsh-Bohmer, KA, and Zandi, PP

Subjects
Neurodegenerative, Neurosciences, Dementia, Brain Disorders, Aging, Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD), Alzheimer's Disease, Prevention, Clinical Research, Acquired Cognitive Impairment, Neurological, Acetaminophen, Adolescent, Adult, Aged, Aged, 80 and over, Alzheimer Disease, Amyloid beta-Peptides, Analgesics, Non-Narcotic, Anti-Inflammatory Agents, Non-Steroidal, Aspirin, Cohort Studies, Female, Humans, Male, Middle Aged, Neuroprotective Agents, Peptide Fragments, Proportional Hazards Models, Prospective Studies, Risk Factors, Clinical Sciences, Cognitive Sciences, Neurology & Neurosurgery
Abstract

IntroductionObservational studies show reduced incidence of Alzheimer dementia (AD) in users of nonsteroidal anti-inflammatory drugs (NSAIDs). One hypothesis holds that the subset of NSAIDs known as selective A beta(42)-lowering agents (SALAs) is responsible for this apparent reduction in AD risk.MethodsWe pooled individual-level data from six prospective studies to obtain a sufficient sample to examine AD risk in users of SALA vs non-SALA NSAIDs.ResultsOf 13,499 initially dementia-free participants (70,863 person-years), 820 developed incident AD. Users of NSAIDs (29.6%) showed reduced risk of AD (adjusted hazard ratio [aHR] 0.77, 95% CI 0.65-0.91). The point estimates were similar for SALAs (aHR 0.87, CI 0.72-1.04) and non-SALAs (aHR 0.75, CI 0.56-1.01). Because 573 NSAID users (14.5%) reported taking both a SALA and non-SALA, we examined their use alone and in combination. Resulting aHRs were 0.82 (CI 0.67-0.99) for SALA only, 0.60 (CI 0.40-0.90) for non-SALA only, and 0.87 (CI 0.57-1.33) for both NSAIDs (Wald test for differences, p = 0.32). The 40.7% of participants who used aspirin also showed reduced risk of AD, even when they used no other NSAIDs (aHR 0.78, CI 0.66-0.92). By contrast, there was no association with use of acetaminophen (aHR 0.93, CI 0.76-1.13).ConclusionsIn this pooled dataset, nonsteroidal anti-inflammatory drug (NSAID) use reduced the risk of Alzheimer dementia (AD). However, there was no apparent advantage in AD risk reduction for the subset of NSAIDs shown to selectively lower A beta(42), suggesting that all conventional NSAIDs including aspirin have a similar protective effect in humans.

Published
2008

6. No advantage of A beta 42-lowering NSAIDs for prevention of Alzheimer dementia in six pooled cohort studies.

Author

Szekely, CA, Green, RC, Breitner, JCS, Østbye, T, Beiser, AS, Corrada, MM, Dodge, HH, Ganguli, M, Kawas, CH, Kuller, LH, Psaty, BM, Resnick, SM, Wolf, PA, Zonderman, AB, Welsh-Bohmer, KA, and Zandi, PP

Subjects
Humans, Alzheimer Disease, Acetaminophen, Aspirin, Peptide Fragments, Analgesics, Non-Narcotic, Neuroprotective Agents, Anti-Inflammatory Agents, Non-Steroidal, Proportional Hazards Models, Risk Factors, Cohort Studies, Prospective Studies, Adolescent, Adult, Aged, Aged, 80 and over, Middle Aged, Female, Male, Amyloid beta-Peptides, Analgesics, Non-Narcotic, Anti-Inflammatory Agents, Non-Steroidal, and over, Neurology & Neurosurgery, Clinical Sciences, Neurosciences, Cognitive Sciences
Abstract

IntroductionObservational studies show reduced incidence of Alzheimer dementia (AD) in users of nonsteroidal anti-inflammatory drugs (NSAIDs). One hypothesis holds that the subset of NSAIDs known as selective A beta(42)-lowering agents (SALAs) is responsible for this apparent reduction in AD risk.MethodsWe pooled individual-level data from six prospective studies to obtain a sufficient sample to examine AD risk in users of SALA vs non-SALA NSAIDs.ResultsOf 13,499 initially dementia-free participants (70,863 person-years), 820 developed incident AD. Users of NSAIDs (29.6%) showed reduced risk of AD (adjusted hazard ratio [aHR] 0.77, 95% CI 0.65-0.91). The point estimates were similar for SALAs (aHR 0.87, CI 0.72-1.04) and non-SALAs (aHR 0.75, CI 0.56-1.01). Because 573 NSAID users (14.5%) reported taking both a SALA and non-SALA, we examined their use alone and in combination. Resulting aHRs were 0.82 (CI 0.67-0.99) for SALA only, 0.60 (CI 0.40-0.90) for non-SALA only, and 0.87 (CI 0.57-1.33) for both NSAIDs (Wald test for differences, p = 0.32). The 40.7% of participants who used aspirin also showed reduced risk of AD, even when they used no other NSAIDs (aHR 0.78, CI 0.66-0.92). By contrast, there was no association with use of acetaminophen (aHR 0.93, CI 0.76-1.13).ConclusionsIn this pooled dataset, nonsteroidal anti-inflammatory drug (NSAID) use reduced the risk of Alzheimer dementia (AD). However, there was no apparent advantage in AD risk reduction for the subset of NSAIDs shown to selectively lower A beta(42), suggesting that all conventional NSAIDs including aspirin have a similar protective effect in humans.

Published
2008

7. Free testosterone and risk for Alzheimer disease in older men

Author

Moffat, SD, Zonderman, AB, Metter, EJ, Kawas, C, Blackman, MR, Harman, SM, and Resnick, SM

Subjects
Acquired Cognitive Impairment, Neurosciences, Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD), Clinical Research, Dementia, Aging, Alzheimer's Disease, Brain Disorders, Neurodegenerative, Adult, Aged, Aged, 80 and over, Alzheimer Disease, Baltimore, Comorbidity, Follow-Up Studies, Humans, Male, Middle Aged, Proportional Hazards Models, Prospective Studies, Risk, Risk Factors, Sex Hormone-Binding Globulin, Testosterone, Clinical Sciences, Cognitive Sciences, Neurology & Neurosurgery
Abstract

ObjectiveTo investigate the relationships between age-associated decreases in endogenous serum total testosterone (T) and a free T index (FTI) in men and the subsequent development of Alzheimer disease (AD).MethodThe authors used a prospective, longitudinal design with follow-up in men since 1958. Participants were from the Baltimore Longitudinal Study of Aging, a community-dwelling volunteer sample with baseline ages of 32 to 87 years. All subjects were free of AD at baseline T assessment. Five hundred seventy-four men assessed at multiple time points were followed for a mean of 19.1 years (range, 4 to 37 years). Diagnoses of AD were based on biennial physical, neurologic, and neuropsychological evaluations.ResultsDiagnosis of AD was associated inversely with FTI by itself and after adjustments for age, education, smoking status, body mass index, diabetes, any cancer diagnoses, and hormone supplements. In separate analyses, total T and sex hormone binding globulin were not significant predictors after adjustment with covariates. Increases in the FTI were associated with decreased risk of AD (hazard ratio = 0.74; 95% CI = 0.57 to 0.96), a 26% decrease for each 10-nmol/nmol FTI increase.ConclusionsCalculated free testosterone concentrations were lower in men who developed Alzheimer disease, and this difference occurred before diagnosis. Future research may determine whether higher endogenous free testosterone levels offer protection against a diagnosis of Alzheimer disease in older men.

Published
2004

8. Visual memory predicts Alzheimer’s disease more than a decade before diagnosis

Author

Kawas, CH, Corrada, MM, Brookmeyer, R, Morrison, A, Resnick, SM, Zonderman, AB, and Arenberg, D

Subjects
Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD), Prevention, Alzheimer's Disease, Brain Disorders, Neurodegenerative, Neurosciences, Acquired Cognitive Impairment, Aging, Clinical Research, Dementia, Detection, screening and diagnosis, 4.1 Discovery and preclinical testing of markers and technologies, Neurological, Aged, Aged, 80 and over, Alzheimer Disease, Chronic Disease, Cohort Studies, Comorbidity, Female, Humans, Intelligence Tests, Longitudinal Studies, Male, Memory Disorders, Middle Aged, Neuropsychological Tests, Predictive Value of Tests, Proportional Hazards Models, Risk, Risk Assessment, Sensitivity and Specificity, Visual Perception, Clinical Sciences, Cognitive Sciences, Neurology & Neurosurgery
Abstract

BackgroundRecent studies have suggested that AD may reflect a chronic process that begins many years before the clinical expression of dementia. The current study examines premorbid Benton Visual Retention Test (BVRT) and Wechsler Adult Intelligence Scale-vocabulary (WAIS-voc) test scores in order to determine whether long-term deficits in these tests can predict the development of AD decades later in the Baltimore Longitudinal Study of Aging (BLSA).MethodParticipants are volunteers from the BLSA, a multidisciplinary study of normal aging conducted by the National Institute on Aging. A total of 1,425 BLSA participants who were older than 60 years were included in the analyses. Cox proportional hazards models were used to estimate the relative risk of developing AD associated with BVRT and WAIS-voc scores at different time periods up to 20 years before the diagnosis of AD.ResultsThe relative risks for 6 or more BVRT errors vs less than 6 errors at 1 to 3, 3 to 5, 5 to 10, and 10 to 15 years before the diagnosis of AD were 5.69, 2.11, 1.76, and 1.83 (p < 0.05). The relative risk for 15 or more years before diagnosis was not significant (p > 0.10). WAIS-voc scores were not significantly associated with the risk of AD in any time period.ConclusionsA greater number of errors on the BVRT is associated with an increased risk of AD up to 15 years later. Poor visual memory performance may represent an early expression of AD years before diagnosis. This result suggests the need to continue to revise views on the natural history of AD and the possibility of an increased window of opportunity for preventive treatment before definitive diagnosis.

Published
2003

9. The Relationship Between Longitudinal Declines in Dehydroepiandrosterone Sulfate Concentrations and Cognitive Performance in Older Men

Author

Moffat, SD, Zonderman, AB, Harman, SM, Blackman, MR, Kawas, C, and Resnick, SM

Subjects
Clinical Research, Complementary and Integrative Health, Behavioral and Social Science, Neurosciences, Aging, Mental Health, Adult, Aged, Aged, 80 and over, Biomarkers, Cognition, Dehydroepiandrosterone Sulfate, Enzyme-Linked Immunosorbent Assay, Humans, Male, Middle Aged, Prospective Studies, Psychological Tests, Psychomotor Performance, Reference Values, Clinical Sciences, Opthalmology and Optometry, Public Health and Health Services
Abstract

BackgroundThe observation that dehydroepiandrosterone (DHEA) concentrations decrease markedly with age has led to the hypothesis that declining DHEA concentrations may contribute to age-related changes in cognition. In the United States, DHEA is widely available as an over-the-counter supplement that individuals are using in an effort to ameliorate age-related cognitive and physical changes.ObjectiveTo investigate the relationship between age-associated decreases in endogenous DHEA sulfate (DHEA-S) concentrations and declines in neuropsychological performance in a prospective, longitudinal study.MethodsThe subjects were 883 men from a community-dwelling volunteer sample in the Baltimore Longitudinal Study of Aging. The men were aged 22 to 91 years at the initial visit, and they were followed up for as long as 31 years (mean, 11. 55 years), with biennial reassessments of multiple cognitive domains and contemporaneous measurement of serum DHEA-S concentrations. Outcome measures were the results of cognitive tests of verbal and visual memory, 2 tests of mental status, phonemic and semantic word fluency tests, and measures of visuomotor scanning and attention. Serum DHEA-S concentrations were determined by standard radioimmunoassay.ResultsNeither the rates of decline in mean DHEA-S concentrations nor the mean DHEA-S concentrations within individuals were related to cognitive status or cognitive decline. A comparison between the highest and lowest DHEA-S quartiles revealed no cognitive differences, despite the fact that these groups differed in endogenous DHEA-S concentration by more than a factor of 4 for a mean duration of 12 years.ConclusionOur longitudinal results augment those of previous prospective studies by suggesting that the decline in endogenous DHEA-S concentration is independent of cognitive status and cognitive decline in healthy aging men.

Published
2000

10. Effects of age and dementia on the trail making test

Author

Rasmusson, DX, Zonderman, AB, Kawas, C, and Resnick, SM

Subjects
Clinical Psychology, Neurosciences, Psychology, Cognitive Sciences
Abstract

Trail Making Test (TMT) performance was investigated in 765 elderly volunteers (age range 60 to 96 years), 58 of whom met DSM-III-R criteria for dementia and 40 dementia 'suspects,' who showed mild changes in one or two cognitive domains. Cross-sectional analyses of the 667 nondemented participants, revealed significant age effects in completion times for both Parts A and B. Prevalence of errors increased with age on Part B, but not on Part A. Two-year longitudinal changes were examined in a subset of the nondemented sample (n = 385). Significant slowing was found for Part B, but not for Part A, with older age groups showing the greatest change. Error rates did not increase. Dementia status accounted for a significant proportion of the variance in completion times after accounting for age, education, and gender. Receiver operating characteristic analyses suggest that the TMT may be useful in screening for cognitive dysfunction.

Published
1998

11. Changes in immediate visual memory predict cognitive impairment.

Author

Zonderman, AB, Giambra, LM, Arenberg, D, Resnick, SM, Costa, PT, and Kawas, CH

Subjects
Clinical Psychology, Neurosciences, Psychology, Cognitive Sciences
Abstract

Six-year changes in immediate visual memory performance assessed by the Benton Visual Retention (BVR) test predicted Alzheimer's disease (AD) prior to its onset. Subjects of this study were 371 community-dwelling adult participants in the Baltimore Longitudinal Study of Aging, seven of whom received probable or definite AD diagnoses using DSM-III-R and NINCDS-ADRDA criteria. Subjects with diagnoses of AD had larger changes in immediate memory performance over the 6-year interval prior to the estimated onset of their disease than subjects without AD. Six-year longitudinal change as well as level in immediate visual memory performance also predicted subsequent cognitive performance 6-15 and 16-22 years later, even after adjusting for the influences of age, general ability, and initial immediate memory. These results provide evidence that change and level in immediate visual memory performance has long-term prognostic significance over as many as 16-22 years. These results further suggest that change in recent memory performance, an important component in AD diagnoses, may be an important precursor of the development of the disease.

Published
1995

12. Adult life span changes in immediate visual memory and verbal intelligence.

Author

Giambra, LM, Arenberg, D, Kawas, C, Zonderman, AB, and Costa, PT

Subjects
Humans, Longitudinal Studies, Cross-Sectional Studies, Individuality, Intelligence, Memory, Short-Term, Pattern Recognition, Visual, Mental Status Schedule, Neuropsychological Tests, Aging, Vocabulary, Adolescent, Adult, Aged, Aged, 80 and over, Middle Aged, Female, Male, Neurosciences, Behavioral and Social Science, Neurological, Mental Health, Experimental Psychology, Psychology, Cognitive Sciences
Abstract

A sample of 558 women and 1,163 men 17 to 102 years old, screened for neurodegenerative and neuropsychiatric disease, was administered tests of immediate visual memory (Benton Visual Retention Test) and crystallized intelligence (Wechsler Adult Intelligence Scale Vocabulary subtest) from 1 to 5 times over 27.7 years. Cross-sectional and longitudinal evidence led to the conclusion that the 65-74-year decade was a watershed for decremental changes in immediate visual memory and verbal intelligence. Age accounted for considerably less variance in vocabulary than in immediate memory. The proportion of individuals whose longitudinal trajectories were contrary to group trends decreased substantially with increased age; observed age changes remained when analyses were restricted to individuals who had perfect or near-perfect mental status scores. Selected neuronal loss and slower reproduction times were considered as possible causes.

Published
1995

17. GWAS and colocalization analyses implicate carotid intima-media thickness and carotid plaque loci in cardiovascular outcomes

Author

Franceschini, N, Giambartolomei, C, de Vries, PS, Finan, C, Bis, JC, Huntley, RP, Lovering, RC, Tajuddin, SM, Winkler, TW, Graff, M, Kavousi, M, Dale, C, Smith, AV, Hofer, E, van Leeuwen, EM, Nolte, IM, Lu, L, Scholz, M, Sargurupremraj, M, Pitkänen, N, Franzén, O, Joshi, PK, Noordam, R, Marioni, RE, Hwang, SJ, Musani, SK, Schminke, U, Palmas, W, Isaacs, A, Correa, A, Zonderman, AB, Hofman, A, Teumer, A, Cox, AJ, Uitterlinden, AG, Wong, A, Smit, AJ, Newman, AB, Britton, A, Ruusalepp, A, Sennblad, B, Hedblad, B, Pasaniuc, B, Penninx, BW, Langefeld, CD, Wassel, CL, Tzourio, C, Fava, C, Baldassarre, D, O’Leary, DH, Teupser, D, Kuh, D, Tremoli, E, Mannarino, E, Grossi, E, Boerwinkle, E, Schadt, EE, Ingelsson, E, Veglia, F, Rivadeneira, F, Beutner, F, Chauhan, G, Heiss, G, Snieder, H, Campbell, H, Völzke, H, Markus, HS, Deary, IJ, Jukema, JW, de Graaf, J, Price, J, Pott, J, Hopewell, JC, Liang, J, Thiery, J, Engmann, J, Gertow, K, Rice, K, Taylor, KD, Dhana, K, Kiemeney, LALM, Lind, L, Raffield, LM, Launer, LJ, Holdt, LM, Dörr, M, Dichgans, M, Traylor, M, Sitzer, M, Kumari, M, Kivimaki, M, Nalls, MA, Melander, O, Raitakari, O, Franco, OH, Rueda-Ochoa, OL, Roussos, P, Whincup, PH, Amouyel, P, and Giral, P

Subjects
Aging, MEGASTROKE Consortium, Quantitative Trait Loci, ADAMTS9 Protein, Coronary Disease, Cardiovascular, Polymorphism, Single Nucleotide, Carotid Intima-Media Thickness, Protein-Lysine 6-Oxidase, Risk Factors, Genetics, 2.1 Biological and endogenous factors, Humans, Genetic Predisposition to Disease, cardiovascular diseases, Aetiology, Polymorphism, Heart Disease - Coronary Heart Disease, Plaque, Atherosclerotic, Human Genome, Single Nucleotide, Atherosclerosis, Plaque, Atherosclerotic, Brain Disorders, Stroke, Heart Disease, cardiovascular system, Amino Acid Oxidoreductases, Lod Score, Genome-Wide Association Study
Abstract

© 2018, The Author(s). Carotid artery intima media thickness (cIMT) and carotid plaque are measures of subclinical atherosclerosis associated with ischemic stroke and coronary heart disease (CHD). Here, we undertake meta-analyses of genome-wide association studies (GWAS) in 71,128 individuals for cIMT, and 48,434 individuals for carotid plaque traits. We identify eight novel susceptibility loci for cIMT, one independent association at the previously-identified PINX1 locus, and one novel locus for carotid plaque. Colocalization analysis with nearby vascular expression quantitative loci (cis-eQTLs) derived from arterial wall and metabolic tissues obtained from patients with CHD identifies candidate genes at two potentially additional loci, ADAMTS9 and LOXL4. LD score regression reveals significant genetic correlations between cIMT and plaque traits, and both cIMT and plaque with CHD, any stroke subtype and ischemic stroke. Our study provides insights into genes and tissue-specific regulatory mechanisms linking atherosclerosis both to its functional genomic origins and its clinical consequences in humans.

Published
2018

18. Discovery and fine-mapping of adiposity loci using high density imputation of genome-wide association studies in individuals of African ancestry: African ancestry anthropometry genetics consortium

Author

Ng, MCY, Graff, M, Lu, Y, Justice, AE, Mudgal, P, Liu, CT, Young, K, Yanek, LR, Feitosa, MF, Wojczynski, MK, Rand, K, Brody, JA, Cade, BE, Dimitrov, L, Duan, Q, Guo, X, Lange, LA, Nalls, MA, Okut, H, Tajuddin, SM, Tayo, BO, Vedantam, S, Bradfield, JP, Chen, G, Chen, WM, Chesi, A, Irvin, MR, Padhukasahasram, B, Smith, JA, Zheng, W, Allison, MA, Ambrosone, CB, Bandera, EV, Bartz, TM, Berndt, SI, Bernstein, L, Blot, WJ, Bottinger, EP, Carpten, J, Chanock, SJ, Chen, YDI, Conti, DV, Cooper, RS, Fornage, M, Freedman, BI, Garcia, M, Goodman, PJ, Hsu, YHH, Hu, J, Huff, CD, Ingles, SA, John, EM, Kittles, R, Klein, E, Li, J, McKnight, B, Nayak, U, Nemesure, B, Ogunniyi, A, Olshan, A, Press, MF, Rohde, R, Rybicki, BA, Salako, B, Sanderson, M, Shao, Y, Siscovick, DS, Stanford, JL, Stevens, VL, Stram, A, Strom, SS, Vaidya, D, Witte, JS, Yao, J, Zhu, X, Ziegler, RG, Zonderman, AB, Adeyemo, A, Ambs, S, Cushman, M, Faul, JD, Hakonarson, H, Levin, AM, Nathanson, KL, and Ware, EB

Abstract

© 2017 Public Library of Science. All rights reserved. Genome-wide association studies (GWAS) have identified >300 loci associated with measures of adiposity including body mass index (BMI) and waist-to-hip ratio (adjusted for BMI, WHRadjBMI), but few have been identified through screening of the African ancestry genomes. We performed large scale meta-analyses and replications in up to 52,895 individuals for BMI and up to 23,095 individuals for WHRadjBMIfrom the African Ancestry Anthropometry Genetics Consortium (AAAGC) using 1000 Genomes phase 1 imputed GWAS to improve coverage of both common and low frequency variants in the low linkage disequilibrium African ancestry genomes. In the sex-combined analyses, we identified one novel locus (TCF7L2/HABP2) for WHRadjBMIand eight previously established loci at P < 5×10−8: seven for BMI, and one for WHRadjBMIin African ancestry individuals. An additional novel locus (SPRYD7/DLEU2) was identified for WHRadjBMIwhen combined with European GWAS. In the sex-stratified analyses, we identified three novel loci for BMI (INTS10/LPL and MLC1 in men, IRX4/IRX2 in women) and four for WHRadjBMI(SSX2IP, CASC8, PDE3B and ZDHHC1/HSD11B2 in women) in individuals of African ancestry or both African and European ancestry. For four of the novel variants, the minor allele frequency was low (

Published
2017

19. Trans-ethnic meta-analysis of white blood cell phenotypes

Author

Keller, Margaux F, Reiner, Alexander P, Okada, Yukinori, van Rooij, Frank J. A, Johnson, Andrew D, Chen, Ming Huei, Smith, Albert V, Morris, Andrew P, Tanaka, Toshiko, Ferrucci, Luigi, Zonderman, Alan B, Lettre, Guillaume, Harris, Tamara, Garcia, Melissa, Bandinelli, Stefania, Qayyum, Rehan, Yanek, Lisa R, Becker, Diane M, Becker, Lewis C, Kooperberg, Charles, Keating, Brendan, Reis, Jared, Tang, Hua, Boerwinkle, Eric, Kamatani, Yoichiro, Matsuda, Koichi, Kamatani, Naoyuki, Nakamura, Yusuke, Kubo, Michiaki, Liu, Simin, Dehghan, Abbas, Felix, Janine F, Hofman, Albert, Uitterlinden, André G, van Duijn, Cornelia M, Franco, Oscar H, Longo, Dan L, Singleton, Andrew B, Psaty, Bruce M, Evans, Michelle K, Cupples, L. Adrienne, Rotter, Jerome I, O'Donnell, Christopher J, Takahashi, Atsushi, Wilson, James G, Ganesh, Santhi K, Nalls, Mike A, Arepalli, S, Bandinelli, S, Biffi, A, Bis, Jc, Boerwinkle, E, Chakravarti, A, Chen, Mh, Chong, S, Coresh, J, Couper, Dj, Cupples, L, Dehghan, A, Do'Ring, A, Eiriksdottir, G, Felix, Jf, Ferrucci, L, Folsom, Ar, Fox, Cs, Frayling, Tm, Ganesh, Sk, Garcia, M, Garner, Sf, Gasparini, Paolo, Gieger, C, Glazer, Nl, Gouskova, Na, Greinacher, A, Gudnason, V, Harris, Tb, Hernandez, Dg, Hofman, A, Illig, T, Kamatani, Y, Kamatani, N, Kubo, M, Kuhnel, B, Lagou, V, Lettre, G, Levi, D, Lin, J, Liu, Y, Longo, Dl, Lumley, T, Mangino, M, Matsuda, K, Meisinger, C, Melzer, D, Menzel, S, Moore, M, Nakamura, Y, Nalls, Ma, Nauck, M, O'Donnell, Cj, Okada, Y, Oostra, Ba, Ouwehand, Wh, Patel, Kv, Pirastu, Nicola, Pistis, Giorgio, Prokisch, H, Prokopenko, I, Psaty, Bm, Reiner, Ap, Rendon, A, Sambrook, J, Singleton, Ab, Smith, Av, Soranzo, N, Spector, Td, Stephens, J, Stumvoll, M, Takahashi, A, Tanaka, T, Taylor, K, Teumer, A, Thein, Sl, To'Njes, A, Toniolo, D, Tsunoda, T, Uitterlinden, Ag, van Duijn CM, van Rooij FJ, Vo'Lker, U, Vo'Lzke, H, Wichmann, H., Wiggins, Kl, Wilson, Jg, Witteman, Jc, Wood, Ar, Yamamoto, K, Yang, Q, Zakai, Na, Austin, Ma, Becker, Dm, Britton, A, Chen, Z, Couper, D, Curb, J, Dean, E, Eaton, Cb, Evans, Mk, Fornage, M, Grant, Sf, Hernandez, D, Kamatini, N, Keating, Bj, Lacroix, A, Lange, La, Liu, S, Lohman, K, Mathias, R, Meng, Y, Mohler ER 3rd, Musani, S, Palmer, Cd, Papanicolaou, Gj, Snively, Bm, Tang, H, Taylor HA Jr, Thomson, C, Yanek, Lr, Yang, L, Ziv, E, Zonderman, Ab, Higasa, K, Hirota, T, Hosono, N, Kumasaka, N, Ohmiya, H, Tamari, M, Yamaguchi Kabata, Y, Yamamoto, K., Epidemiology, Medical Informatics, Urology, Erasmus MC other, Internal Medicine, Keller, Margaux F, Reiner, Alexander P, Okada, Yukinori, van Rooij, Frank J. A, Johnson, Andrew D, Chen, Ming Huei, Smith, Albert V, Morris, Andrew P, Tanaka, Toshiko, Ferrucci, Luigi, Zonderman, Alan B, Lettre, Guillaume, Harris, Tamara, Garcia, Melissa, Bandinelli, Stefania, Qayyum, Rehan, Yanek, Lisa R, Becker, Diane M, Becker, Lewis C, Kooperberg, Charle, Keating, Brendan, Reis, Jared, Tang, Hua, Boerwinkle, Eric, Kamatani, Yoichiro, Matsuda, Koichi, Kamatani, Naoyuki, Nakamura, Yusuke, Kubo, Michiaki, Liu, Simin, Dehghan, Abba, Felix, Janine F, Hofman, Albert, Uitterlinden, André G, van Duijn, Cornelia M, Franco, Oscar H, Longo, Dan L, Singleton, Andrew B, Psaty, Bruce M, Evans, Michelle K, Cupples, L. Adrienne, Rotter, Jerome I, O'Donnell, Christopher J, Takahashi, Atsushi, Wilson, James G, Ganesh, Santhi K, Nalls, Mike A, Arepalli, S, Bandinelli, S, Biffi, A, Bis, Jc, Boerwinkle, E, Chakravarti, A, Chen, Mh, Chong, S, Coresh, J, Couper, Dj, Cupples, L, Dehghan, A, Do'Ring, A, Eiriksdottir, G, Felix, Jf, Ferrucci, L, Folsom, Ar, Fox, C, Frayling, Tm, Ganesh, Sk, Garcia, M, Garner, Sf, Gasparini, Paolo, Gieger, C, Glazer, Nl, Gouskova, Na, Greinacher, A, Gudnason, V, Harris, Tb, Hernandez, Dg, Hofman, A, Illig, T, Kamatani, Y, Kamatani, N, Kubo, M, Kuhnel, B, Lagou, V, Lettre, G, Levi, D, Lin, J, Liu, Y, Longo, Dl, Lumley, T, Mangino, M, Matsuda, K, Meisinger, C, Melzer, D, Menzel, S, Moore, M, Nakamura, Y, Nalls, Ma, Nauck, M, O'Donnell, Cj, Okada, Y, Oostra, Ba, Ouwehand, Wh, Patel, Kv, Pirastu, Nicola, Pistis, Giorgio, Prokisch, H, Prokopenko, I, Psaty, Bm, Reiner, Ap, Rendon, A, Sambrook, J, Singleton, Ab, Smith, Av, Soranzo, N, Spector, Td, Stephens, J, Stumvoll, M, Takahashi, A, Tanaka, T, Taylor, K, Teumer, A, Thein, Sl, To'Njes, A, Toniolo, D, Tsunoda, T, Uitterlinden, Ag, van Duijn, Cm, van Rooij, Fj, Vo'Lker, U, Vo'Lzke, H, Wichmann, H., Wiggins, Kl, Wilson, Jg, Witteman, Jc, Wood, Ar, Yamamoto, K, Yang, Q, Zakai, Na, Austin, Ma, Becker, Dm, Britton, A, Chen, Z, Couper, D, Curb, J, Dean, E, Eaton, Cb, Evans, Mk, Fornage, M, Grant, Sf, Hernandez, D, Kamatini, N, Keating, Bj, Lacroix, A, Lange, La, Liu, S, Lohman, K, Mathias, R, Meng, Y, Mohler ER, 3rd, Musani, S, Palmer, Cd, Papanicolaou, Gj, Snively, Bm, Tang, H, Taylor HA, Jr, Thomson, C, Yanek, Lr, Yang, L, Ziv, E, Zonderman, Ab, Higasa, K, Hirota, T, Hosono, N, Kumasaka, N, Ohmiya, H, Tamari, M, Yamaguchi Kabata, Y, and Yamamoto, K.

Subjects
Linkage disequilibrium, Genotype, Quantitative Trait Loci, White blood cell count, Single-nucleotide polymorphism, Genome-wide association study, Quantitative trait locus, Biology, Polymorphism, Single Nucleotide, Linkage Disequilibrium, White People, white blood cell phenotypes, Leukocyte Count, SDG 3 - Good Health and Well-being, Asian People, Polymorphism (computer science), Genetics, Leukocytes, Humans, Allele, Molecular Biology, Genetics (clinical), White blood cell count, Trans-ethnic meta-analysis, white blood cell phenotypes, Genome, Human, Association Studies Articles, Bayes Theorem, General Medicine, Heritability, Black or African American, Phenotype, Trans-ethnic meta-analysis, Genome-Wide Association Study
Abstract

White blood cell (WBC) count is a common clinical measure used as a predictor of certain aspects of human health, including immunity and infection status. WBC count is also a complex trait that varies among individuals and ancestry groups. Differences in linkage disequilibrium structure and heterogeneity in allelic effects are expected to play a role in the associations observed between populations. Prior genome-wide association study (GWAS) meta-analyses have identified genomic loci associated with WBC and its subtypes, but much of the heritability of these phenotypes remains unexplained. Using GWAS summary statistics for over 50 000 individuals from three diverse populations (Japanese, African-American and European ancestry), a Bayesian model methodology was employed to account for heterogeneity between ancestry groups. This approach was used to perform a trans-ethnic meta-analysis of total WBC, neutrophil and monocyte counts. Ten previously known associations were replicated and six new loci were identified, including several regions harboring genes related to inflammation and immune cell function. Ninety-five percent credible interval regions were calculated to narrow the association signals and fine-map the putatively causal variants within loci. Finally, a conditional analysis was performed on the most significant SNPs identified by the trans-ethnic meta-analysis (MA), and nine secondary signals within loci previously associated with WBC or its subtypes were identified. This work illustrates the potential of trans-ethnic analysis and ascribes a critical role to multi-ethnic cohorts and consortia in exploring complex phenotypes with respect to variants that lie outside the European-biased GWAS pool.

Published
2014

20. Meta-Analysis of Genome-Wide Association Studies in African Americans Provides Insights into the Genetic Architecture of Type 2 Diabetes

Author

Ng, MCY, Shriner, D, Chen, BH, Li, J, Chen, WM, Guo, X, Liu, J, Bielinski, SJ, Yanek, LR, Nalls, MA, Comeau, ME, Rasmussen-Torvik, LJ, Jensen, RA, Evans, DS, Sun, YV, An, P, Patel, SR, Lu, Y, Long, J, Armstrong, LL, Wagenknecht, L, Yang, L, Snively, BM, Palmer, ND, Mudgal, P, Langefeld, CD, Keene, KL, Freedman, BI, Mychaleckyj, JC, Nayak, U, Raffel, LJ, Goodarzi, MO, Chen, YDI, Taylor, HA, Correa, A, Sims, M, Couper, DJ, Pankow, JS, Boerwinkle, E, Adeyemo, A, Doumatey, A, Chen, G, Mathias, RA, Vaidya, D, Singleton, AB, Zonderman, AB, Igo, RP, Sedor, JR, Zondervan, KT, Kabagambe, EK, Siscovick, DS, McKnight, B, Rice, K, Liu, Y, Hsueh, WC, Zhao, W, Bielak, LF, Kraja, A, Province, MA, Bottinger, EP, Gottesman, O, Cai, Q, Zheng, W, Blot, WJ, Lowe, WL, Pacheco, JA, Crawford, DC, Yang, TP, Wilk, A, Grundberg, E, Tsoka, S, Rich, SS, Hayes, MG, Shu, XO, and Loos, RJF

Subjects
endocrine system diseases
Abstract

© 2014. Type 2 diabetes (T2D) is more prevalent in African Americans than in Europeans. However, little is known about the genetic risk in African Americans despite the recent identification of more than 70 T2D loci primarily by genome-wide association studies (GWAS) in individuals of European ancestry. In order to investigate the genetic architecture of T2D in African Americans, the MEta-analysis of type 2 DIabetes in African Americans (MEDIA) Consortium examined 17 GWAS on T2D comprising 8,284 cases and 15,543 controls in African Americans in stage 1 analysis. Single nucleotide polymorphisms (SNPs) association analysis was conducted in each study under the additive model after adjustment for age, sex, study site, and principal components. Meta-analysis of approximately 2.6 million genotyped and imputed SNPs in all studies was conducted using an inverse variance-weighted fixed effect model. Replications were performed to follow up 21 loci in up to 6,061 cases and 5,483 controls in African Americans, and 8,130 cases and 38,987 controls of European ancestry. We identified three known loci (TCF7L2, HMGA2 and KCNQ1) and two novel loci (HLA-B and INS-IGF2) at genome-wide significance (4.15×10−94

Published
2014

21. No advantage of aβ42-lowering NSAIDs for prevention of Alzheimer dementia in six pooled cohort studies symbol

Author

Szekely, CA, Green, RC, Breitner, JCS, Østbye, T, Beiser, AS, Corrada, MM, Dodge, HH, Ganguli, M, Kawas, CH, Kuller, LH, Psaty, BM, Resnick, SM, Wolf, PA, Zonderman, AB, Welsh-Bohmer, KA, and Zandi, PP

Abstract

Observational studies show reduced incidence of Alzheimer dementia (AD) in users of nonsteroidal anti-inflammatory drugs (NSAIDs). One hypothesis holds that the subset of NSAIDs known as selective Aβ42-lowering agents (SALAs) is responsible for this apparent reduction in AD risk. We pooled individual-level data from six prospective studies to obtain a sufficient sample to examine AD risk in users of SALA vs non-SALA NSAIDs. Of 13,499 initially dementia-free participants (70,863 person-years), 820 developed incident AD. Users of NSAIDs (29.6%) showed reduced risk of AD (adjusted hazard ratio [aHR] 0.77, 95% CI 0.65-0.91). The point estimates were similar for SALAs (aHR 0.87, CI 0.72-1.04) and non-SALAs (aHR 0.75, CI 0.56-1.01). Because 573 NSAID users (14.5%) reported taking both a SALA and non-SALA, we examined their use alone and in combination. Resulting aHRs were 0.82 (CI 0.67-0.99) for SALA only, 0.60 (CI 0.40-0.90) for non-SALA only, and 0.87 (CI 0.57-1.33) for both NSAIDs (Wald test for differences, p = 0.32). The 40.7% of participants who used aspirin also showed reduced risk of AD, even when they used no other NSAIDs (aHR 0.78, CI 0.66-0.92). By contrast, there was no association with use of acetaminophen (aHR 0.93, CI 0.76-1.13). In this pooled dataset, nonsteroidal anti-inflammatory drug (NSAID) use reduced the risk of Alzheimer dementia (AD). However, there was no apparent advantage in AD risk reduction for the subset of NSAIDs shown to selectively lower Aβ42suggesting that all conventional NSAIDs including aspirin have a similar protective effect in humans. © 2008 Lippincott Williams & Wilkins, Inc.

Published
2008

22. Serum ferritin levels associated with increased risk for developing CHD in a low-income urban population.

Author

Olesnevich ME, Kuczmarski MF, Mason M, Fang C, Zonderman AB, Evans MK, Olesnevich, Meghan E, Fanelli Kuczmarski, Marie, Mason, Marc, Fang, Chengshun, Zonderman, Alan B, and Evans, Michele K

Abstract

Objective: The present study examined the association of serum ferritin with CHD risk using the Framingham Heart Study's 10-year risk algorithm.Design: Ordinal logistic regression modelling was used to interpret risk. Proportional odds modelling assessed four divisions of ranked CHD risk (4, high; 3, increased; 2, slight; 1, minimal), separately by sex.Setting: Baltimore, MD, USA.Subjects: African-American and white participants (n 1823) from baseline of the Healthy Aging in Neighborhoods of Diversity across the Life Span (HANDLS) study, aged 30-64 years.Results: For men, there was a 0·5 % increase in risk for every 10-unit rise in serum ferritin (pmol/l). Other significant predictors included increased BMI, white race, unemployment and C-reactive protein ≥9·5 mg/l. For women, there was a 1·5 % [corrected] increase in risk per 10-unit rise in serum ferritin (pmol/l). Other significant predictors included increased BMI, lower education, unemployment and C-reactive protein ≥9·5 mg/l.Conclusions: Serum ferritin is a significant predictor of 10-year hard CHD risk for HANDLS study participants, a low-income, urban population. Serum ferritin, independent of elevated C-reactive protein, was associated with increased 10-year CHD risk for HANDLS participants. To our knowledge, these data provide the first evidence of the role of serum ferritin as a risk factor for hard CHD in African-American and white postmenopausal women in the USA. Future research on cardiovascular events from this prospective study may confirm the association. [ABSTRACT FROM AUTHOR]

Published
2012
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24. Neuroticism, depressive symptoms, and serum BDNF.

Author

Terracciano A, Lobina M, Piras MG, Mulas A, Cannas A, Meirelles O, Sutin AR, Zonderman AB, Uda M, Crisponi L, Schlessinger D, Terracciano, Antonio, Lobina, Monia, Piras, Maria Grazia, Mulas, Antonella, Cannas, Alessandra, Meirelles, Osorio, Sutin, Angelina R, Zonderman, Alan B, and Uda, Manuela

Published
2011
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27. Age, Alzheimer's disease and dementia in the Baltimore Longitudinal Study of Ageing.

Author

Dolan D, Troncoso J, Resnick SM, Crain BJ, Zonderman AB, O'Brien RJ, Dolan, David, Troncoso, Juan, Resnick, Susan M, Crain, Barbara J, Zonderman, Alan B, and O'Brien, Richard J

Abstract

Recent studies suggest that dementia in the most elderly (90 years of age and above) is only modestly related to Alzheimer's disease pathology. This raises the possibility that other, as yet unknown, disease processes may underlie dementia in this rapidly growing demographic group, and that efforts designed to combat Alzheimer's disease may not be appropriate for treating dementia in very elderly subjects. To study this question more closely, we examined the relationship between neocortical Alzheimer-type brain pathology and dementia in consecutive autopsies from 209 participants in the Baltimore Longitudinal Study of Ageing, a prospective longitudinal cohort study of the effect of ageing on cognition. Almost half of the cohort was older than 90 years of age at death. We found that several measures of neocortical Alzheimer's pathology, including the Consortium to Establish a Registry of Alzheimer's Disease neuritic plaque score and the Braak neurofibrillary tangle score, remained significant predictors of dementia, independent of age. In participants older than 90 years of age, intracranial atherosclerosis emerged as an important predictor of dementia in subjects with low Alzheimer's pathology scores, but did not mitigate the importance or population attributable risk of high Alzheimer's pathology scores on the odds of dementia. There was evidence that the threshold score for neurofibrillary pathology to cause dementia increased in the oldest subjects, but this was offset by an overall increase in neurofibrillary pathology in this age group. We conclude that neocortical Alzheimer's disease pathology remains significantly correlated with dementia, independent of age. In the most elderly, atherosclerosis also emerged as a cause of dementia in subjects with low Alzheimer's pathology scores. We found no evidence for a significant number of elderly subjects having dementia without an apparent cause. [ABSTRACT FROM AUTHOR]

Published
2010
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29. Healthy aging in neighborhoods of diversity across the life span (HANDLS): overcoming barriers to implementing a longitudinal, epidemiologic, urban study of health, race, and socioeconomic status.

Author

Evans MK, Lepkowski JM, Powe NR, LaVeist T, Kuczmarski MF, Zonderman AB, Evans, Michele K, Lepkowski, James M, Powe, Neil R, LaVeist, Thomas, Kuczmarski, Marie Fanelli, and Zonderman, Alan B

Abstract

Objective: Examine the influences of race, socioeconomic status, sex, and age on barriers to participation in a study of cross-sectional differences and longitudinal changes in health-related outcomes.Methods: We designed a multidisciplinary, community-based, prospective longitudinal epidemiologic study among socioeconomically diverse African Americans and Whites. We recruited 3722 participants from Baltimore, Md. with a mean age of 47.7 (range 30-64) years, 45% males; 2200 African Americans (59%) and 1522 whites (41%); 41% reported household incomes below the 125% poverty delimiter.Results: There were no significant age differences associated with sex or race. Participants below the 125% poverty delimiter were slightly younger than those above the delimiter. Age, race, and sex, but not poverty status, were associated with the likelihood of a physical examination. Older participants, women, and Whites were more likely to complete their examinations. Among those who completed their examinations, there were no age differences associated with sex and poverty status, but African Americans were negligibly younger than Whites.Conclusions: Although some literature suggests that minorities and low-income people are less willing to participate in clinical research, these baseline data suggest that African Americans individuals and individuals from households with incomes below 125% of the poverty level are at least as willing to participate in observational clinical studies as Whites and higher income individuals of similar age and sex. [ABSTRACT FROM AUTHOR]

Published
2010

34. Association of adiposity status and changes in early to mid-adulthood with incidence of Alzheimer's disease.

Author

Beydoun MA, Lhotsky A, Wang Y, Dal Forno G, An Y, Metter EJ, Ferrucci L, O'Brien R, and Zonderman AB

Abstract

Adiposity status and change are potential risk factors for Alzheimer's disease (AD). The authors used data on 2,322 participants in the Baltimore Longitudinal Study of Aging to analyze the relation between AD incidence and adiposity in Cox proportional hazards models, with adjustment for sociodemographic factors and smoking status. Body mass index (BMI; weight (kg)/height (m)(2)) and waist circumference at specific ages were predicted by empirical Bayes estimators from mixed-effects regression models. After a median of 23.4 years of follow-up between 1958 and 2006, 187 participants developed AD. Among men, being underweight (BMI or=30) at age 30, 40, or 45 years and jointly centrally obese (waist circumference >or=80th percentile) at age 30, 35, or 50 years increased AD risk (HR = 6.57, 95% CI: 1.96, 22.02). Women who lost weight (BMI change <10th percentile) between ages 30 and 45 years were also at increased risk (HR = 2.02, 95% CI: 1.06, 3.85). Weight gain among men (BMI change >90th percentile) between ages 30 and 50 years increased AD risk (HR = 3.70, 95% CI: 1.43, 9.56). Future studies should identify age- and gender-specific optimal weights and weight-loss strategies for preventing AD and investigate potential mechanisms. [ABSTRACT FROM AUTHOR]

Published
2008
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36. Children of persons with Alzheimer disease: what does the future hold?

Author

Jarvik L, LaRue A, Blacker D, Gatz M, Kawas C, McArdle JJ, Morris JC, Mortimer JA, Ringman JM, Ercoli L, Freimer N, Gokhman I, Manly JJ, Plassman BL, Rasgon N, Roberts JS, Sunderland T, Swan GE, Wolf PA, and Zonderman AB

Abstract

Children of persons with Alzheimer disease (AD), as a group, face an increased risk of developing AD. Many of them, throughout their adult lives, seek input on how to reduce their chances of one day suffering their parent's fate. We examine the state of knowledge with respect to risk and protective factors for AD and recommend a research agenda with special emphasis on AD offspring. [ABSTRACT FROM AUTHOR]

Published
2008
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44. Impact of common genetic determinants of Hemoglobin A1c on type 2 diabetes risk and diagnosis in ancestrally diverse populations: A transethnic genome-wide meta-analysis

Author

Wheeler, E, Leong, A, Liu, C-T, Hivert, M-F, Strawbridge, RJ, Podmore, C, Li, M, Yao, J, Sim, X, Hong, J, Chu, AY, Zhang, W, Wang, X, Chen, P, Maruthur, NM, Porneala, BC, Sharp, SJ, Jia, Y, Kabagambe, EK, Chang, L-C, Chen, W-M, Elks, CE, Evans, DS, Fan, Q, Giulianini, F, Go, MJ, Hottenga, J-J, Hu, Y, Jackson, AU, Kanoni, S, Kim, YJ, Kleber, ME, Ladenvall, C, Lecoeur, C, Lim, S-H, Lu, Y, Mahajan, A, Marzi, C, Nalls, MA, Navarro, P, Nolte, IM, Rose, LM, Rybin, DV, Sanna, S, Shi, Y, Stram, DO, Takeuchi, F, Tan, SP, Van Der Most, PJ, Van Vliet-Ostaptchouk, JV, Wong, A, Yengo, L, Zhao, W, Goel, A, Martinez Larrad, MT, Radke, D, Salo, P, Tanaka, T, Van Iperen, EPA, Abecasis, G, Afaq, S, Alizadeh, BZ, Bertoni, AG, Bonnefond, A, Böttcher, Y, Bottinger, EP, Campbell, H, Carlson, OD, Chen, C-H, Cho, YS, Garvey, WT, Gieger, C, Goodarzi, MO, Grallert, H, Hamsten, A, Hartman, CA, Herder, C, Hsiung, CA, Huang, J, Igase, M, Isono, M, Katsuya, T, Khor, C-C, Kiess, W, Kohara, K, Kovacs, P, Lee, J, Lee, W-J, Lehne, B, Li, H, Liu, J, Lobbens, S, Luan, J, Lyssenko, V, Meitinger, T, Miki, T, Miljkovic, I, Moon, S, Mulas, A, Müller, G, Müller-Nurasyid, M, Nagaraja, R, Nauck, M, Pankow, JS, Polasek, O, Prokopenko, I, Ramos, PS, Rasmussen-Torvik, L, Rathmann, W, Rich, SS, Robertson, NR, Roden, M, Roussel, R, Rudan, I, Scott, RA, Scott, WR, Sennblad, B, Siscovick, DS, Strauch, K, Sun, L, Swertz, M, Tajuddin, SM, Taylor, KD, Teo, Y-Y, Tham, YC, Tönjes, A, Wareham, NJ, Willemsen, G, Wilsgaard, T, Hingorani, AD, EPIC-CVD Consortium, EPIC-InterAct Consortium, Lifelines Cohort Study, Egan, J, Ferrucci, L, Hovingh, GK, Jula, A, Kivimaki, M, Kumari, M, Njølstad, I, Palmer, CNA, Serrano Ríos, M, Stumvoll, M, Watkins, H, Aung, T, Blüher, M, Boehnke, M, Boomsma, DI, Bornstein, Chambers, JC, Chasman, DI, Chen, Y-DI, Chen, Y-T, Cheng, C-Y, Cucca, F, De Geus, EJC, Deloukas, P, Evans, MK, Fornage, M, Friedlander, Y, Froguel, P, Groop, L, Gross, MD, Harris, TB, Hayward, C, Heng, C-K, Ingelsson, E, Kato, N, Kim, B-J, Koh, W-P, Kooner, JS, Körner, A, Kuh, D, Kuusisto, J, Laakso, M, Lin, X, Liu, Y, Loos, RJF, Magnusson, PKE, März, W, McCarthy, MI, Oldehinkel, AJ, Ong, KK, Pedersen, NL, Pereira, MA, Peters, A, Ridker, PM, Sabanayagam, C, Sale, M, Saleheen, D, Saltevo, J, Schwarz, PE, Sheu, WHH, Snieder, H, Spector, TD, Tabara, Y, Tuomilehto, J, Van Dam, RM, Wilson, JG, Wilson, JF, Wolffenbuttel, BHR, Wong, TY, Wu, J-Y, Yuan, J-M, Zonderman, AB, Soranzo, N, Guo, X, Roberts, DJ, Florez, JC, Sladek, R, Dupuis, J, Morris, AP, Tai, E-S, Selvin, E, Rotter, JI, Langenberg, C, Barroso, I, and Meigs, JB

Subjects
Hemoglobin A, Glycosylated, endocrine system diseases, Diabetes Mellitus, Type 2, phenotype, genetic variation, nutritional and metabolic diseases, humans, 3. Good health, Genome-Wide Association Study, risk
Abstract

BACKGROUND: Glycated hemoglobin (HbA1c) is used to diagnose type 2 diabetes (T2D) and assess glycemic control in patients with diabetes. Previous genome-wide association studies (GWAS) have identified 18 HbA1c-associated genetic variants. These variants proved to be classifiable by their likely biological action as erythrocytic (also associated with erythrocyte traits) or glycemic (associated with other glucose-related traits). In this study, we tested the hypotheses that, in a very large scale GWAS, we would identify more genetic variants associated with HbA1c and that HbA1c variants implicated in erythrocytic biology would affect the diagnostic accuracy of HbA1c. We therefore expanded the number of HbA1c-associated loci and tested the effect of genetic risk-scores comprised of erythrocytic or glycemic variants on incident diabetes prediction and on prevalent diabetes screening performance. Throughout this multiancestry study, we kept a focus on interancestry differences in HbA1c genetics performance that might influence race-ancestry differences in health outcomes. METHODS & FINDINGS: Using genome-wide association meta-analyses in up to 159,940 individuals from 82 cohorts of European, African, East Asian, and South Asian ancestry, we identified 60 common genetic variants associated with HbA1c. We classified variants as implicated in glycemic, erythrocytic, or unclassified biology and tested whether additive genetic scores of erythrocytic variants (GS-E) or glycemic variants (GS-G) were associated with higher T2D incidence in multiethnic longitudinal cohorts (N = 33,241). Nineteen glycemic and 22 erythrocytic variants were associated with HbA1c at genome-wide significance. GS-G was associated with higher T2D risk (incidence OR = 1.05, 95% CI 1.04-1.06, per HbA1c-raising allele, p = 3 × 10-29); whereas GS-E was not (OR = 1.00, 95% CI 0.99-1.01, p = 0.60). In Europeans and Asians, erythrocytic variants in aggregate had only modest effects on the diagnostic accuracy of HbA1c. Yet, in African Americans, the X-linked G6PD G202A variant (T-allele frequency 11%) was associated with an absolute decrease in HbA1c of 0.81%-units (95% CI 0.66-0.96) per allele in hemizygous men, and 0.68%-units (95% CI 0.38-0.97) in homozygous women. The G6PD variant may cause approximately 2% (N = 0.65 million, 95% CI 0.55-0.74) of African American adults with T2D to remain undiagnosed when screened with HbA1c. Limitations include the smaller sample sizes for non-European ancestries and the inability to classify approximately one-third of the variants. Further studies in large multiethnic cohorts with HbA1c, glycemic, and erythrocytic traits are required to better determine the biological action of the unclassified variants. CONCLUSIONS: As G6PD deficiency can be clinically silent until illness strikes, we recommend investigation of the possible benefits of screening for the G6PD genotype along with using HbA1c to diagnose T2D in populations of African ancestry or groups where G6PD deficiency is common. Screening with direct glucose measurements, or genetically-informed HbA1c diagnostic thresholds in people with G6PD deficiency, may be required to avoid missed or delayed diagnoses.

45. Change in depressive symptoms in the Baltimore Longitudinal Study of Aging.

Author

Davey A, Halverson CF Jr., Zonderman AB, and Costa PT Jr.

Abstract

Depressive symptoms have been represented in the research and clinical literature in terms of both an episodic phenomenon and as enduring individual differences. We investigated depressive symptoms longitudinally in a sample of older adults. Participants were 737 individuals (M(Age) = 73 years initially, 39% women) in the Baltimore Longitudinal Study of Aging who provided biennial Center for Epidemiological Studies-Depression data on up to five occasions over an 8-year period. We found both trait and state-residual variability, with symptoms increasing longitudinally on all subscales and accounting for an approximately 1-point increase per decade. Trait-like variability accounted for at least two thirds of the reliable variance. Interindividual differences were consistent over time, but occasion-specific variability diminished across occasions. [ABSTRACT FROM AUTHOR]

Published
2004
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47. A catalog of genetic loci associated with kidney function from analyses of a million individuals

Author

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, Pina Concas, Maria, 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, Hickst, 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., Shilpa Josyula, Navya, 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., Jen-Mai Lee, Jeannette, Lehne, Benjamin, Lehtimäki, Terho, Lieb, Wolfgang, Cohort Study, Lifelines, Lim, Su-Chi, Lind, Lars, Lindgren, Cecilia M., Liu, Jun, Liu, Jianjun, Loeffler, Markus, Loos, Ruth J. F., Lucae, Susanne, Ann Lukas, Mary, Lyytikäinen, Leo-Pekka, Mägi, Reedik, Magnusson, Patrik K. E., Mahajan, Anubha, Martin, Nicholas G., Martins, Jade, März, Winfried, Mascalzoni, Deborah, Matsuda, Koichi, Christa Meisinger, Meitinger, Thomas, Melander, Olle, Metspalu, Andres, Mikaelsdottir, Evgenia K., Milaneschi, Yuri, Miliku, Kozeta, Mishra, Pashupati P., Veteran Program, V. A. Million, 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, üwe, 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., Markus Scholz, Teumer, Alexander, Köttgen, Anna, Pattaro, Cristian, Groningen Institute for Organ Transplantation (GIOT), Lifestyle Medicine (LM), Groningen Kidney Center (GKC), Cardiovascular Centre (CVC), Interdisciplinary Centre Psychopathology and Emotion regulation (ICPE), Life Course Epidemiology (LCE), Internal Medicine, Epidemiology, Erasmus MC other, Pediatrics, Psychiatry, APH - Mental Health, APH - Digital Health, Wuttke, M, Li, Y, Li, M, Sieber, Kb, Feitosa, Mf, Gorski, M, Tin, A, Wang, L, Chu, Ay, Hoppmann, A, Kirsten, H, Giri, A, Chai, Jf, Sveinbjornsson, G, Tayo, Bo, Nutile, T, Fuchsberger, C, Marten, J, Cocca, M, Ghasemi, S, Xu, Y, Horn, K, Noce, D, van der Most, Pj, Sedaghat, S, Yu, Z, Akiyama, M, Afaq, S, Ahluwalia, T, Almgren, P, Amin, N, Ärnlöv, J, Bakker, Sjl, Bansal, N, Baptista, D, Bergmann, S, Biggs, Ml, Biino, G, Boehnke, M, Boerwinkle, E, Boissel, M, Bottinger, Ep, Boutin, T, Brenner, H, Brumat, M, Burkhardt, R, Butterworth, A, Campana, Eric, Campbell, A, Campbell, H, Canouil, M, Carroll, Rj, Catamo, E, Chambers, Jc, Chee, Ml, Chen, X, Cheng, Cy, Cheng, Y, Christensen, K, Cifkova, R, Ciullo, M, Concas, Mp, Cook, Jp, Coresh, J, Corre, T, Sala, Cf, Cusi, D, Danesh, J, Daw, Ew, de Borst, Mh, De Grandi, A, de Mutsert, R, de Vries, Apj, Degenhardt, F, Delgado, G, Demirkan, A, Di Angelantonio, E, Dittrich, K, Divers, J, Dorajoo, R, Eckardt, Ku, Ehret, G, Elliott, P, Endlich, K, Evans, Mk, Felix, Jf, Foo, Vhx, Franco, Oh, Franke, A, Freedman, Bi, Freitag-Wolf, S, Friedlander, Y, Froguel, P, Gansevoort, Rt, Gao, H, Gasparini, P, Gaziano, Jm, Giedraitis, V, Gieger, C, Girotto, G, Giulianini, F, Gögele, M, Gordon, Sd, Gudbjartsson, Df, Gudnason, V, Haller, T, Hamet, P, Harris, Tb, Hartman, Ca, Hayward, C, Hellwege, Jn, Heng, Ck, Hicks, Aa, Hofer, E, Huang, W, Hutri-Kähönen, N, Hwang, Sj, Ikram, Ma, Indridason, O, Ingelsson, E, Ising, M, Jaddoe, Vwv, Jakobsdottir, J, Jonas, Jb, Joshi, Pk, Josyula, N, Jung, B, Kähönen, M, Kamatani, Y, Kammerer, Cm, Kanai, M, Kastarinen, M, Kerr, Sm, Khor, Cc, Kiess, W, Kleber, Me, Koenig, W, Kooner, J, Körner, A, Kovacs, P, Kraja, At, Krajcoviechova, A, Kramer, H, Krämer, Bk, Kronenberg, F, Kubo, M, Kühnel, B, Kuokkanen, M, Kuusisto, J, La Bianca, M, Laakso, M, Lange, La, Langefeld, Cd, Lee, Jj, Lehne, B, Lehtimäki, T, Lieb, W, Lifelines Cohort, Study, Lim, Sc, Lind, L, Lindgren, Cm, Liu, J, Loeffler, M, Loos, Rjf, Lucae, S, Lukas, Ma, Lyytikäinen, Lp, Mägi, R, Magnusson, Pke, Mahajan, A, Martin, Ng, Martins, J, März, W, Mascalzoni, D, Matsuda, K, Meisinger, C, Meitinger, T, Melander, O, Metspalu, A, Mikaelsdottir, Ek, Milaneschi, Y, Miliku, K, Mishra, Pp, V. A., Million Veteran Program, Mohlke, Kl, Mononen, N, Montgomery, Gw, Mook-Kanamori, Do, Mychaleckyj, Jc, Nadkarni, Gn, Nalls, Ma, Nauck, M, Nikus, K, Ning, B, Nolte, Im, Noordam, R, O'Connell, J, O'Donoghue, Ml, Olafsson, I, Oldehinkel, Aj, Orho-Melander, M, Ouwehand, Wh, Padmanabhan, S, Palmer, Nd, Palsson, R, Penninx, Bwjh, Perls, T, Perola, M, Pirastu, M, Pirastu, N, Pistis, G, Podgornaia, Ai, Polasek, O, Ponte, B, Porteous, Dj, Poulain, T, Pramstaller, Pp, Preuss, Mh, Prins, Bp, Province, Ma, Rabelink, Tj, Raffield, Lm, Raitakari, Ot, Reilly, Df, Rettig, R, Rheinberger, M, Rice, Km, Ridker, Pm, Rivadeneira, F, Rizzi, F, Roberts, Dj, Robino, A, Rossing, P, Rudan, I, Rueedi, R, Ruggiero, D, Ryan, Ka, Saba, Y, Sabanayagam, C, Salomaa, V, Salvi, E, Saum, Ku, Schmidt, H, Schmidt, R, Schöttker, B, Schulz, Ca, Schupf, N, Shaffer, Cm, Shi, Y, Smith, Av, Smith, Bh, Soranzo, N, Spracklen, Cn, Strauch, K, Stringham, Hm, Stumvoll, M, Svensson, Po, Szymczak, S, Tai, E, Tajuddin, Sm, Tan, Nyq, Taylor, Kd, Teren, A, Tham, Yc, Thiery, J, Thio, Chl, Thomsen, H, Thorleifsson, G, Toniolo, D, Tönjes, A, Tremblay, J, Tzoulaki, I, Uitterlinden, Ag, Vaccargiu, S, van Dam, Rm, van der Harst, P, van Duijn, Cm, Velez Edward, Dr, Verweij, N, Vogelezang, S, Völker, U, Vollenweider, P, Waeber, G, Waldenberger, M, Wallentin, L, Wang, Yx, Wang, C, Waterworth, Dm, Bin Wei, W, White, H, Whitfield, Jb, Wild, Sh, Wilson, Jf, Wojczynski, Mk, Wong, C, Wong, Ty, Xu, L, Yang, Q, Yasuda, M, Yerges-Armstrong, Lm, Zhang, W, Zonderman, Ab, Rotter, Ji, Bochud, M, Psaty, Bm, Vitart, V, Wilson, Jg, Dehghan, A, Parsa, A, Chasman, Di, Ho, K, Morris, Ap, Devuyst, O, Akilesh, S, Pendergrass, Sa, Sim, X, Böger, Ca, Okada, Y, Edwards, Tl, Snieder, H, Stefansson, K, Hung, Am, Heid, Im, Scholz, M, Teumer, A, Köttgen, A, and Pattaro, C.

Subjects
catalog, Inheritance Patterns, Hasso-Plattner-Institut für Digital Engineering GmbH, Genome-wide association study, Disease, Kidney Function Tests, Bioinformatics, DISEASE, 0302 clinical medicine, Uromodulin/urine, kidney function, 11 Medical and Health Sciences, Genetics & Heredity, ddc:616, 0303 health sciences, Kidney, Genome-wide association, HERITABILITY, GENOME-WIDE ASSOCIATION, COMMON VARIANTS, RENAL-FUNCTION, TRANS-EQTLS, METAANALYSIS, TRANSPORTER, CLASSIFICATION, INTEGRATION, Chromosome Mapping, 3. Good health, Phenotype, medicine.anatomical_structure, Medical genetics, Common variants, Renal function, Trans-EQTLS, Metaanalysis, Heritability, Transporter, Life Sciences & Biomedicine, Glomerular Filtration Rate, Metaanalysi, medicine.medical_specialty, Genotype, European Continental Ancestry Group, Quantitative Trait Loci, Common variant, Quantitative trait locus, Biology, Polymorphism, Single Nucleotide, Article, White People, V. A. Million Veteran Program, 03 medical and health sciences, Quantitative Trait, Heritable, Lifelines Cohort Study, Uromodulin, Genetics, medicine, Humans, Genetic Predisposition to Disease, Renal Insufficiency, Chronic, Genetic Association Studies, 030304 developmental biology, Genetic association, Science & Technology, urogenital system, association, genetic loci, 06 Biological Sciences, medicine.disease, Renal Insufficiency, Chronic/genetics/physiopathology/urine, Genetic Association Studies/methods, ddc:000, 030217 neurology & neurosurgery, Developmental Biology, Genome-Wide Association Study, Kidney disease
Abstract

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.

Published
2019

48. Multi-ancestry genome-wide gene-smoking interaction study of 387,272 individuals identifies new loci associated with serum lipids

Author

Bentley, Amy R, Sung, Yun J, Brown, Michael R, Winkler, Thomas W, Kraja, Aldi T, Ntalla, Ioanna, Schwander, Karen, Chasman, Daniel I, Lim, Elise, Deng, Xuan, Guo, Xiuqing, Liu, Jingmin, Lu, Yingchang, Cheng, Ching-Yu, Sim, Xueling, Vojinovic, Dina, Huffman, Jennifer E, Musani, Solomon K, Li, Changwei, Feitosa, Mary F, Richard, Melissa A, Noordam, Raymond, Baker, Jenna, Chen, Guanjie, Aschard, Hugues, Bartz, Traci M, Ding, Jingzhong, Dorajoo, Rajkumar, Manning, Alisa K, Rankinen, Tuomo, Smith, Albert V, Tajuddin, Salman M, Zhao, Wei, Graff, Mariaelisa, Alver, Maris, Boissel, Mathilde, Chai, Jin Fang, Chen, Xu, Divers, Jasmin, Evangelou, Evangelos, Gao, Chuan, Goel, Anuj, Hagemeijer, Yanick, Harris, Sarah E, Hartwig, Fernando P, He, Meian, Horimoto, Andrea RVR, Hsu, Fang-Chi, Hung, Yi-Jen, Jackson, Anne U, Kasturiratne, Anuradhani, Komulainen, Pirjo, Kuehnel, Brigitte, Leander, Karin, Lin, Keng-Hung, Luan, Jian'an, Lyytikainen, Leo-Pekka, Matoba, Nana, Nolte, Ilja M, Pietzner, Maik, Prins, Bram, Riaz, Muhammad, Robino, Antonietta, Said, M Abdullah, Schupf, Nicole, Scott, Robert A, Sofer, Tamar, Stancakova, Alena, Takeuchi, Fumihiko, Tayo, Bamidele O, van der Most, Peter J, Varga, Tibor V, Wang, Tzung-Dau, Wang, Yajuan, Ware, Erin B, Wen, Wanqing, Xiang, Yong-Bing, Yanek, Lisa R, Zhang, Weihua, Zhao, Jing Hua, Adeyemo, Adebowale, Afaq, Saima, Amin, Najaf, Amini, Marzyeh, Arking, Dan E, Arzumanyan, Zorayr, Aung, Tin, Ballantyne, Christie, Barr, R Graham, Bielak, Lawrence F, Boerwinkle, Eric, Bottinger, Erwin P, Broeckel, Ulrich, Brown, Morris, Cade, Brian E, Campbell, Archie, Canouil, Mickael, Charumathi, Sabanayagam, Chen, Yii-Der Ida, Christensen, Kaare, Concas, Maria Pina, Connell, John M, de las Fuentes, Lisa, de Silva, H Janaka, de Vries, Paul S, Doumatey, Ayo, Duan, Qing, Eaton, Charles B, Eppinga, Ruben N, Faul, Jessica D, Floyd, James S, Forouhi, Nita G, Forrester, Terrence, Friedlander, Yechiel, Gandin, Ilaria, Gao, He, Ghanbari, Mohsen, Gharib, Sina A, Gigante, Bruna, Giulianini, Franco, Grabe, Hans J, Gu, C Charles, Harris, Tamara B, Heikkinen, Sami, Heng, Chew-Kiat, Hirata, Makoto, Hixson, James E, Ikram, M Arfan, Jia, Yucheng, Joehanes, Roby, Johnson, Craig, Jonas, Jost Bruno, Justice, Anne E, Katsuya, Tomohiro, Khor, Chiea Chuen, Kilpelainen, Tuomas O, Koh, Woon-Puay, Kolcic, Ivana, Kooperberg, Charles, Krieger, Jose E, Kritchevsky, Stephen B, Kubo, Michiaki, Kuusisto, Johanna, Lakka, Timo A, Langefeld, Carl D, Langenberg, Claudia, Launer, Lenore J, Lehne, Benjamin, Lewis, Cora E, Li, Yize, Liang, Jingjing, Lin, Shiow, Liu, Ching-Ti, Liu, Jianjun, Liu, Kiang, Loh, Marie, Lohman, Kurt K, Louie, Tin, Luzzi, Anna, Magi, Reedik, Mahajan, Anubha, Manichaikul, Ani W, McKenzie, Colin A, Meitinger, Thomas, Metspalu, Andres, Milaneschi, Yuri, Milani, Lili, Mohlke, Karen L, Momozawa, Yukihide, Morris, Andrew P, Murray, Alison D, Nalls, Mike A, Nauck, Matthias, Nelson, Christopher P, North, Kari E, O'Connell, Jeffrey R, Palmer, Nicholette D, Papanicolau, George J, Pedersen, Nancy L, Peters, Annette, Peyser, Patricia A, Polasek, Ozren, Poulter, Neil, Raitakari, Olli T, Reiner, Alex P, Renstrom, Frida, Rice, Treva K, Rich, Stephen S, Robinson, Jennifer G, Rose, Lynda M, Rosendaal, Frits R, Rudan, Igor, Schmidt, Carsten O, Schreiner, Pamela J, Scott, William R, Sever, Peter, Shi, Yuan, Sidney, Stephen, Sims, Mario, Smith, Jennifer A, Snieder, Harold, Starr, John M, Strauch, Konstantin, Stringham, Heather M, Tan, Nicholas YQ, Tang, Hua, Taylor, Kent D, Teo, Yik Ying, Tham, Yih Chung, Tiemeier, Henning, Turner, Stephen T, Uitterlinden, Andre G, van Heemst, Diana, Waldenberger, Melanie, Wang, Heming, Wang, Lan, Wang, Lihua, Wei, Wen Bin, Williams, Christine A, Sr, Wilson Gregory, Wojczynski, Mary K, Yao, Jie, Young, Kristin, Yu, Caizheng, Yuan, Jian-Min, Zhou, Jie, Zonderman, Alan B, Becker, Diane M, Boehnke, Michael, Bowden, Donald W, Chambers, John C, Cooper, Richard S, de Faire, Ulf, Deary, Ian J, Elliott, Paul, Esko, Tonu, Farrall, Martin, Franks, Paul W, Freedman, Barry I, Froguel, Philippe, Gasparini, Paolo, Gieger, Christian, Horta, Bernardo L, Juang, Jyh-Ming Jimmy, Kamatani, Yoichiro, Kammerer, Candace M, Kato, Norihiro, Kooner, Jaspal S, Laakso, Markku, Laurie, Cathy C, Lee, I-Te, Lehtimaki, Terho, Magnusson, Patrik KE, Oldehinkel, Albertine J, Penninx, Brenda WJH, Pereira, Alexandre C, Rauramaa, Rainer, Redline, Susan, Samani, Nilesh J, Scott, James, Shu, Xiao-Ou, van der Harst, Pim, Wagenknecht, Lynne E, Wang, Jun-Sing, Wang, Ya Xing, Wareham, Nicholas J, Watkins, Hugh, Weir, David R, Wickremasinghe, Ananda R, Wu, Tangchun, Zeggini, Eleftheria, Zheng, Wei, Bouchard, Claude, Evans, Michele K, Gudnason, Vilmundur, Kardia, Sharon LR, Liu, Yongmei, Psaty, Bruce M, Ridker, Paul M, van Dam, Rob M, Mook-Kanamori, Dennis O, Fornage, Myriam, Province, Michael A, Kelly, Tanika N, Fox, Ervin R, Hayward, Caroline, van Duijn, Cornelia M, Tai, E Shyong, Wong, Tien Yin, Loos, Ruth JF, Franceschini, Nora, Rotter, Jerome I, Zhu, Xiaofeng, Bierut, Laura J, Gauderman, W James, Rice, Kenneth, Munroe, Patricia B, Morrison, Alanna C, Rao, Dabeeru C, Rotimi, Charles N, Cupples, L Adrienne, Consortium, COGENT-Kidney, Consortium, EPIC-InterAct, Grp, Understanding Soc Sci, Cohort, Lifelines, National Institutes of Health [Bethesda] (NIH), Washington University School of Medicine in St. Louis, Washington University in Saint Louis (WUSTL), The University of Texas Health Science Center at Houston (UTHealth), Universität Regensburg (UR), Queen Mary University of London (QMUL), Brigham and Women's Hospital [Boston], Harvard Medical School [Boston] (HMS), School of Public Health [Boston], Boston University [Boston] (BU), Los Angeles Biomedical Research Institute (LA BioMed), Fred Hutchinson Cancer Research Center [Seattle] (FHCRC), Icahn School of Medicine at Mount Sinai [New York] (MSSM), Singapore Eye Research Institute [Singapore] (SERI), Duke-NUS Medical School [Singapore], National University of Singapore (NUS), Erasmus University Medical Center [Rotterdam] (Erasmus MC), University of Edinburgh, University of Mississippi Medical Center (UMMC), University of Georgia [USA], Leiden University Medical Center (LUMC), Centre de Bioinformatique, Biostatistique et Biologie Intégrative (C3BI), Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Harvard T.H. Chan School of Public Health, University of Washington [Seattle], Wake Forest University, Genome Institute of Singapore (GIS), Massachusetts General Hospital [Boston], Pennington Biomedical Research Center, Louisiana State University (LSU), Icelandic Heart Association [Kopavogur, Iceland] (IHA), University of Iceland [Reykjavik], University of Michigan [Ann Arbor], University of Michigan System, University of North Carolina [Chapel Hill] (UNC), University of North Carolina System (UNC), University of Tartu, Metabolic functional (epi)genomics and molecular mechanisms involved in type 2 diabetes and related diseases - UMR 8199 - UMR 1283 (GI3M), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre National de la Recherche Scientifique (CNRS), Karolinska Institutet [Stockholm], Wake Forest School of Medicine [Winston-Salem], Wake Forest Baptist Medical Center, Imperial College London, University of Ioannina, University of Oxford [Oxford], University of Groningen [Groningen], Universidade Federal de Pelotas = Federal University of Pelotas (UFPel), University of Bristol [Bristol], Huazhong University of Science and Technology [Wuhan] (HUST), Universidade de São Paulo Medical School (FMUSP), Case Western Reserve University [Cleveland], University of Southern California (USC), This project was largely supported by a grant from the US National Heart, Lung, and Blood Institute of the National Institutes of Health (R01HL118305) and by the Intramural Research Program of the National Human Genome Research Institute of the National Institutes of Health through the Center for Research on Genomics and Global Health (CRGGH). The CRGGH is supported by the National Human Genome Research Institute, the National Institute of Diabetes and Digestive and Kidney Diseases, the Center for Information Technology, and the Office of the Director at the National Institutes of Health (Z01HG200362)., Bentley, Ar, Sung, Yj, Brown, Mr, Winkler, Tw, Kraja, At, Ntalla, I, Schwander, K, Chasman, Di, Lim, E, Deng, X, Guo, X, Liu, J, Lu, Y, Cheng, Cy, Sim, X, Vojinovic, D, Huffman, Je, Musani, Sk, Li, C, Feitosa, Mf, Richard, Ma, Noordam, R, Baker, J, Chen, G, Aschard, H, Bartz, Tm, Ding, J, Dorajoo, R, Manning, Ak, Rankinen, T, Smith, Av, Tajuddin, Sm, Zhao, W, Graff, M, Alver, M, Boissel, M, Chai, Jf, Chen, X, Divers, J, Evangelou, E, Gao, C, Goel, A, Hagemeijer, Y, Harris, Se, Hartwig, Fp, He, M, Horimoto, Arvr, Hsu, Fc, Hung, Yj, Jackson, Au, Kasturiratne, A, Komulainen, P, Kühnel, B, Leander, K, Lin, Kh, Luan, J, Lyytikäinen, Lp, Matoba, N, Nolte, Im, Pietzner, M, Prins, B, Riaz, M, Robino, A, Said, Ma, Schupf, N, Scott, Ra, Sofer, T, Stancáková, A, Takeuchi, F, Tayo, Bo, van der Most, Pj, Varga, Tv, Wang, Td, Wang, Y, Ware, Eb, Wen, W, Xiang, Yb, Yanek, Lr, Zhang, W, Zhao, Jh, Adeyemo, A, Afaq, S, Amin, N, Amini, M, Arking, De, Arzumanyan, Z, Aung, T, Ballantyne, C, Barr, Rg, Bielak, Lf, Boerwinkle, E, Bottinger, Ep, Broeckel, U, Brown, M, Cade, Be, Campbell, A, Canouil, M, Charumathi, S, Chen, Yi, Christensen, K, COGENT-Kidney, Consortium, Concas, Mp, Connell, Jm, de Las Fuentes, L, de Silva, Hj, de Vries, P, Doumatey, A, Duan, Q, Eaton, Cb, Eppinga, Rn, Faul, Jd, Floyd, J, Forouhi, Ng, Forrester, T, Friedlander, Y, Gandin, I, Gao, H, Ghanbari, M, Gharib, Sa, Gigante, B, Giulianini, F, Grabe, Hj, Gu, Cc, Harris, Tb, Heikkinen, S, Heng, Ck, Hirata, M, Hixson, Je, Ikram, Ma, EPIC-InterAct, Consortium, Jia, Y, Joehanes, R, Johnson, C, Jonas, Jb, Justice, Ae, Katsuya, T, Khor, Cc, Kilpeläinen, To, Koh, Wp, Kolcic, I, Kooperberg, C, Krieger, Je, Kritchevsky, Sb, Kubo, M, Kuusisto, J, Lakka, Ta, Langefeld, Cd, Langenberg, C, Launer, Lj, Lehne, B, Lewis, Ce, Li, Y, Liang, J, Lin, S, Liu, Ct, Liu, K, Loh, M, Lohman, Kk, Louie, T, Luzzi, A, Mägi, R, Mahajan, A, Manichaikul, Aw, Mckenzie, Ca, Meitinger, T, Metspalu, A, Milaneschi, Y, Milani, L, Mohlke, Kl, Momozawa, Y, Morris, Ap, Murray, Ad, Nalls, Ma, Nauck, M, Nelson, Cp, North, Ke, O'Connell, Jr, Palmer, Nd, Papanicolau, Gj, Pedersen, Nl, Peters, A, Peyser, Pa, Polasek, O, Poulter, N, Raitakari, Ot, Reiner, Ap, Renström, F, Rice, Tk, Rich, S, Robinson, Jg, Rose, Lm, Rosendaal, Fr, Rudan, I, Schmidt, Co, Schreiner, Pj, Scott, Wr, Sever, P, Shi, Y, Sidney, S, Sims, M, Smith, Ja, Snieder, H, Starr, Jm, Strauch, K, Stringham, Hm, Tan, Nyq, Tang, H, Taylor, Kd, Teo, Yy, Tham, Yc, Tiemeier, H, Turner, St, Uitterlinden, Ag, Understanding Society Scientific, Group, van Heemst, D, Waldenberger, M, Wang, H, Wang, L, Wei, Wb, Williams, Ca, Wilson, G Sr, Wojczynski, Mk, Yao, J, Young, K, Yu, C, Yuan, Jm, Zhou, J, Zonderman, Ab, Becker, Dm, Boehnke, M, Bowden, Dw, Chambers, Jc, Cooper, R, de Faire, U, Deary, Ij, Elliott, P, Esko, T, Farrall, M, Franks, Pw, Freedman, Bi, Froguel, P, Gasparini, P, Gieger, C, Horta, Bl, Juang, Jj, Kamatani, Y, Kammerer, Cm, Kato, N, Kooner, J, Laakso, M, Laurie, Cc, Lee, It, Lehtimäki, T, Lifelines, Cohort, Magnusson, Pke, Oldehinkel, Aj, Penninx, Bwjh, Pereira, Ac, Rauramaa, R, Redline, S, Samani, Nj, Scott, J, Shu, Xo, van der Harst, P, Wagenknecht, Le, Wang, J, Wang, Yx, Wareham, Nj, Watkins, H, Weir, Dr, Wickremasinghe, Ar, Wu, T, Zeggini, E, Zheng, W, Bouchard, C, Evans, Mk, Gudnason, V, Kardia, Slr, Liu, Y, Psaty, Bm, Ridker, Pm, van Dam, Rm, Mook-Kanamori, Do, Fornage, M, Province, Ma, Kelly, Tn, Fox, Er, Hayward, C, van Duijn, Cm, Tai, E, Wong, Ty, Loos, Rjf, Franceschini, N, Rotter, Ji, Zhu, X, Bierut, Lj, Gauderman, Wj, Rice, K, Munroe, Pb, Morrison, Ac, Rao, Dc, Rotimi, Cn, Cupples, La., Luan, Jian'an [0000-0003-3137-6337], Pietzner, Maik [0000-0003-3437-9963], Zhao, Jing Hua [0000-0003-4930-3582], Forouhi, Nita [0000-0002-5041-248X], Langenberg, Claudia [0000-0002-5017-7344], Wareham, Nicholas [0000-0003-1422-2993], Apollo - University of Cambridge Repository, Epidemiology, Neurology, Radiology & Nuclear Medicine, Internal Medicine, Life Course Epidemiology (LCE), Interdisciplinary Centre Psychopathology and Emotion regulation (ICPE), Cardiovascular Centre (CVC), Home Office, Action on Hearing Loss, Imperial College Healthcare NHS Trust- BRC Funding, Medical Research Council (MRC), Universiteit Leiden, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Metabolic functional (epi)genomics and molecular mechanisms involved in type 2 diabetes and related diseases - UMR 8199 - UMR 1283 (EGENODIA (GI3M)), University of Oxford, Psychiatry, Amsterdam Neuroscience - Complex Trait Genetics, APH - Mental Health, and APH - Digital Health

Subjects
Male, Linkage disequilibrium, Blood lipids, Genome-wide association study, VARIANTS, SUSCEPTIBILITY, Environment interaction, Genome, Linkage Disequilibrium, MESH: Genotype, 0302 clinical medicine, MESH: Aged, 80 and over, Genotype, NICOTINE METABOLISM, 11 Medical and Health Sciences, Genetics & Heredity, Aged, 80 and over, Genetics, MESH: Aged, 0303 health sciences, ARCHITECTURE, [STAT.AP]Statistics [stat]/Applications [stat.AP], Genotype imputation, MESH: Middle Aged, CHOLESTEROL, Smoking, MESH: Life Style, Lifelines Cohort, Middle Aged, Lipids, 3. Good health, ENVIRONMENT INTERACTION, GENOTYPE IMPUTATION, RISK LOCI, METAANALYSIS, CIGARETTES, Cholesterol, MESH: Linkage Disequilibrium, MESH: Young Adult, Meta-analysis, Genome-Wide Association Study/methods, Smoking/blood, Medical genetics, Female, EPIC-InterAct Consortium, Life Sciences & Biomedicine, [STAT.ME]Statistics [stat]/Methodology [stat.ME], Adult, Metaanalysi, Understanding Society Scientific Group, medicine.medical_specialty, MESH: Smoking, Adolescent, Genomics, COGENT-Kidney Consortium, Biology, Nicotine metabolism, Risk loci, Metaanalysis, Cigarettes, Article, Young Adult, 03 medical and health sciences, genomics, medicine, Humans, Linkage Disequilibrium/genetics, Life Style, Aged, 030304 developmental biology, MESH: Adolescent, Science & Technology, MESH: Humans, Lipids/blood, MESH: Adult, 06 Biological Sciences, MESH: Lipids, MESH: Male, cardiovascular diseases, [SDV.GEN.GH]Life Sciences [q-bio]/Genetics/Human genetics, genome-wide association studies, MESH: Genome-Wide Association Study, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, [INFO.INFO-BI]Computer Science [cs]/Bioinformatics [q-bio.QM], MESH: Female, 030217 neurology & neurosurgery, Developmental Biology, Genome-Wide Association Study
Abstract

The concentrations of high- and low-density lipoprotein cholesterol and triglycerides are influenced by smoking, but it is unknown whether genetic associations with lipids may be modified by smoking. We conducted a multi-ancestry genome-wide gene-smoking interaction study in 133,805 individuals with follow-up in an additional 253,467 individuals. Combined meta-analyses identified 13 novel loci, some of which were detected only because the association differed by smoking status. Additionally, we demonstrated the importance of including diverse populations, particularly in studies of interactions with lifestyle factors, where genomic and lifestyle differences by ancestry may contribute to novel findings., Editorial summary: A multi-ancestry genome-wide gene-smoking interaction study identifies 13 new loci associated with serum lipids.

Published
2019

50. Racial Discrimination, Religious Coping, and Cardiovascular Disease Risk Among African American Women and Men.

Author

Ashe J, Bentley-Edwards K, Skipper A, Cuevas A, Vieytes CM, Bah K, Evans MK, Zonderman AB, and Waldstein SR

Abstract

Objective: This cross-sectional study examined whether religious coping buffered the associations between racial discrimination and several modifiable cardiovascular disease (CVD) risk factors-systolic and diastolic blood pressure (BP), glycated hemoglobin (HbA1c), body mass index (BMI), and cholesterol-in a sample of African American women and men., Methods: Participant data were taken from the Healthy Aging in Neighborhoods of Diversity Across the Life Span study (N = 815; 55.2% women; 30-64 years old). Racial discrimination and religious coping were self-reported. CVD risk factors were clinically assessed., Results: In sex-stratified hierarchical regression analyses adjusted for age, socioeconomic status, and medication use, findings revealed several significant interactive associations and opposite effects by sex. Among men who experienced racial discrimination, religious coping was negatively related to systolic BP and HbA1c. However, in men reporting no prior discrimination, religious coping was positively related to most risk factors. Among women who had experienced racial discrimination, greater religious coping was associated with higher HbA1c and BMI. The lowest levels of CVD risk were observed among women who seldom used religious coping but experienced discrimination., Conclusion: Religious coping might mitigate the effects of racial discrimination on CVD risk for African American men but not women. Additional work is needed to understand whether reinforcing these coping strategies only benefits those who have experienced discrimination. It is also possible that religion may not buffer the effects of other psychosocial stressors linked with elevated CVD risk., (© 2024. The Author(s).)

Published
2024
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