Browsing by Author "Land, Kenneth C"
Results Per Page
Sort Options
Item Open Access Beta2-adrenergic receptor gene polymorphisms as systemic determinants of healthy aging in an evolutionary context.(Mech Ageing Dev, 2010-05) Kulminski, Alexander M; Culminskaya, Irina; Ukraintseva, Svetlana V; Arbeev, Konstantin G; Land, Kenneth C; Yashin, Anatoli IThe Gln(27)Glu polymorphism but not the Arg(16)Gly polymorphism of the beta2-adrenergic receptor (ADRB2) gene appears to be associated with a broad range of aging-associated phenotypes, including cancers at different sites, myocardial infarction (MI), intermittent claudication (IC), and overall/healthy longevity in the Framingham Heart Study Offspring cohort. The Gln(27)Gln genotype increases risks of cancer, MI and IC, whereas the Glu(27) allele or, equivalently, the Gly(16)Glu(27) haplotype tends to be protective against these diseases. Genetic associations with longevity are of opposite nature at young-old and oldest-old ages highlighting the phenomenon of antagonistic pleiotropy. The mechanism of antagonistic pleiotropy is associated with an evolutionary-driven advantage of carriers of a derived Gln(27) allele at younger ages and their survival disadvantage at older ages as a result of increased risks of cancer, MI and IC. The ADRB2 gene can play an important systemic role in healthy aging in evolutionary context that warrants exploration in other populations.Item Open Access Essays on Fertility and Fertility Preferences in India(2014) Rajan, SowmyaIn this dissertation, I examine at the aggregate and individual levels, why contemporary fertility preferences diverge from actual fertility. I use three waves of cross-sectional survey data from the National Family Health Surveys from India (also known as the Indian Demographic and Health Surveys), fielded in 1992-3, 1998-9 and 2005-6 to investigate the disjuncture between preferences and behavior. The first empirical chapter outlines and operationalizes a new framework to decompose the incongruence between stated preferences and actual fertility into a set of parameters, such as unwanted births, gender preference and postponement of births to later ages, each of which varies in its level and intensity between societies and over time. By delineating the societal constraints that women do not incorporate in their childbearing intentions, this model provides a useful framework to explain variability in fertility in contemporary intermediate- and low-fertility populations. Equally important, the framework provides avenues to enquire into the fundamental structural and cultural correlates producing differences between family size preferences and actual fertility.
Subsequent empirical chapters explore various aspects of fertility preferences in detail. The second chapter probes a key socioeconomic correlate of individual-level fertility preferences, namely educational differences in preferences. In brief, I find that educational differences in family size preferences have considerably converged over time using two-way fixed effects models. However, there is still considerable heterogeneity in the implementation of preferences (as manifested by the use of contraception). Accordingly, in the third chapter, I analyze the multilevel sources of variation in the use of contraception by young women, given that they express a preference to space or stop childbearing. Using multilevel models, I find that community norms play a strong role in the use of contraception by young women to meet their fertility preferences to space or stop childbearing. I argue that community norms are an influential determinant of young women's ability to regulate their own fertility - serving to enhance or constrain their use of contraception to either space or stop childbearing.
Overall, findings from this dissertation highlight the macro-level factors that explain variation in contemporary fertility, of which fertility preferences emerge as a critical parameter. This dissertation also illuminates the growing convergence of fertility preferences across socioeconomic categories, while focusing attention on local community forces that influence fertility behavior even in the face of women's stated preferences.
Item Open Access How genes influence life span: the biodemography of human survival.(Rejuvenation Res, 2012-08) Yashin, Anatoliy I; Wu, Deqing; Arbeev, Konstantin G; Stallard, Eric; Land, Kenneth C; Ukraintseva, Svetlana VBACKGROUND: In genome-wide association studies (GWAS) of human life span, none of the genetic variants has reached the level of genome-wide statistical significance. The roles of such variants in life span regulation remain unclear. DATA AND METHOD: A biodemographic analyses was done of genetic regulation of life span using data on low-significance longevity alleles selected in the earlier GWAS of the original Framingham cohort. RESULTS: Age-specific survival curves considered as functions of the number of longevity alleles exhibit regularities known in demography as "rectangularization" of survival curves. The presence of such pattern confirms observations from experimental studies that regulation of life span involves genes responsible for stress resistance. CONCLUSION: Biodemographic analyses could provide important information about the properties of genes affecting phenotypic traits.Item Open Access Medicalization as a Rising Rational Myth: Population Health Implications, Reproduction, and Public Response(2011) Zheng, HuiIn this dissertation, I study medicalization, a wide spread phenomenon in this world but understudied in the current literature. The main theoretical focus of this dissertation is on expanding the medicalization theories. Questioning the breadth of conceptualization, the feasibility of measurement, and the depth of empirical implications in the extant medicalization theories, this dissertation proposes a new conceptual model of medicalization and further develops a quantitative measure of medicalization by disaggregating it into empirically valid dimensions that could be used to examine how degree of medicalization is related to social outcomes. Specifically, I conceptualize medicalization as an institutionalization process whereby the medical model becomes increasingly dominant in the explanation of health, illness, and other human problems and behavior. Medicalization is multidimensional and is represented by expansions in the three major components of the health care system: increasing medical investment, medical professionalization/specialization, and the relative size of the pharmaceutical industry.
Based on this new conceptual model and measurement, I probe three research questions: (1) how medicalization may impact population health in the context of recent epidemiologic transitions and how this impact may differ by the stages of epidemiologic transition and socioeconomic development; (2) what are the mechanisms that reproduce medicalization; and (3) how the lay public may respond to medicalization, the institution of medicine, and the medical profession.
This dissertation links several lines of theoretical and empirical research from medical sociology, demography, epidemiology, health economics and management, and medical science, and extensively employs OECD Health Data, World Development Indicators, the World Values Survey, the European Values Study data, the U.S. General Social Survey, and the U.S. National Health Interview Survey. It uses several advanced statistical methods, e.g., multiple imputations, latent variable analysis, mixed models, generalized estimating equations models, generalized method of moments models, difference-in-difference models, and hierarchical-age-period-cohort models.
Results for the first research question suggest that various dimensions of medicalization vary in importance on population health and these effects also differ by the stages of epidemiologic transition and socioeconomic development. I discuss the mechanisms linking various dimensions of medicalization to population health and then discuss these findings in the context of epidemiologic transition, fundamental causes of disease and death, and global health movement.
Results for the second research question suggest that medicalization at both the societal and individual levels negatively affect individual subjective health, which leads to increasing health care utilization. These social processes function together to promote and reproduce medicalization at societal level. I discuss several pathways linking medicalization to lower subjective health and other agents of medicalization.
Results for the third research question suggest that American's "confidence in the medical institution and profession" has continuously declined in the last three decades and groups with higher socioeconomic status report lower obedience to doctors' authority, but are more likely to trust doctors' ethics than their counterparts. I discuss the mechanisms for the changes in public confidence in the medical institution and profession, the status of medicine and the medical profession in the era of medicalization, the paradox of opposite trends in attitudes toward medicine and health utilization behavior, and group differences in obedience and trust.
Item Open Access Novel loci and pathways significantly associated with longevity.(Sci Rep, 2016-02-25) Zeng, Yi; Nie, Chao; Min, Junxia; Liu, Xiaomin; Li, Mengmeng; Chen, Huashuai; Xu, Hanshi; Wang, Mingbang; Ni, Ting; Li, Yang; Yan, Han; Zhang, Jin-Pei; Song, Chun; Chi, Li-Qing; Wang, Han-Ming; Dong, Jie; Zheng, Gu-Yan; Lin, Li; Qian, Feng; Qi, Yanwei; Liu, Xiao; Cao, Hongzhi; Wang, Yinghao; Zhang, Lijuan; Li, Zhaochun; Zhou, Yufeng; Wang, Yan; Lu, Jiehua; Li, Jianxin; Qi, Ming; Bolund, Lars; Yashin, Anatoliy; Land, Kenneth C; Gregory, Simon; Yang, Ze; Gottschalk, William; Tao, Wei; Wang, Jian; Wang, Jun; Xu, Xun; Bae, Harold; Nygaard, Marianne; Christiansen, Lene; Christensen, Kaare; Franceschi, Claudio; Lutz, Michael W; Gu, Jun; Tan, Qihua; Perls, Thomas; Sebastiani, Paola; Deelen, Joris; Slagboom, Eline; Hauser, Elizabeth; Xu, Huji; Tian, Xiao-Li; Yang, Huanming; Vaupel, James WOnly two genome-wide significant loci associated with longevity have been identified so far, probably because of insufficient sample sizes of centenarians, whose genomes may harbor genetic variants associated with health and longevity. Here we report a genome-wide association study (GWAS) of Han Chinese with a sample size 2.7 times the largest previously published GWAS on centenarians. We identified 11 independent loci associated with longevity replicated in Southern-Northern regions of China, including two novel loci (rs2069837-IL6; rs2440012-ANKRD20A9P) with genome-wide significance and the rest with suggestive significance (P < 3.65 × 10(-5)). Eight independent SNPs overlapped across Han Chinese, European and U.S. populations, and APOE and 5q33.3 were replicated as longevity loci. Integrated analysis indicates four pathways (starch, sucrose and xenobiotic metabolism; immune response and inflammation; MAPK; calcium signaling) highly associated with longevity (P ≤ 0.006) in Han Chinese. The association with longevity of three of these four pathways (MAPK; immunity; calcium signaling) is supported by findings in other human cohorts. Our novel finding on the association of starch, sucrose and xenobiotic metabolism pathway with longevity is consistent with the previous results from Drosophilia. This study suggests protective mechanisms including immunity and nutrient metabolism and their interactions with environmental stress play key roles in human longevity.Item Open Access Polymorphisms in the ACE and ADRB2 genes and risks of aging-associated phenotypes: the case of myocardial infarction.(Rejuvenation Res, 2010-02) Kulminski, Alexander M; Culminskaya, Irina V; Ukraintseva, Svetlana V; Arbeev, Konstantin G; Akushevich, Igor; Land, Kenneth C; Yashin, Anatoli IMultiple functions of the beta2-adrenergic receptor (ADRB2) and angiotensin-converting enzyme (ACE) genes warrant studies of their associations with aging-related phenotypes. We focus on multimarker analyses and analyses of the effects of compound genotypes of two polymorphisms in the ADRB2 gene, rs1042713 and rs1042714, and 11 polymorphisms of the ACE gene, on the risk of such an aging-associated phenotype as myocardial infarction (MI). We used the data from a genotyped sample of the Framingham Heart Study Offspring (FHSO) cohort (n = 1500) followed for about 36 years with six examinations. The ADRB2 rs1042714 (C-->G) polymorphism and two moderately correlated (r(2) = 0.77) ACE polymorphisms, rs4363 (A-->G) and rs12449782 (A-->G), were significantly associated with risks of MI in this aging cohort in multimarker models. Predominantly linked ACE genotypes exhibited opposite effects on MI risks, e.g., the AA (rs12449782) genotype had a detrimental effect, whereas the predominantly linked AA (rs4363) genotype exhibited a protective effect. This trade-off occurs as a result of the opposite effects of rare compound genotypes of the ACE polymorphisms with a single dose of the AG heterozygote. This genetic trade-off is further augmented by the selective modulating effect of the rs1042714 ADRB2 polymorphism. The associations were not altered by adjustment for common MI risk factors. The results suggest that effects of single specific genetic variants of the ADRB2 and ACE genes on MI can be readily altered by gene-gene or/and gene-environmental interactions, especially in large heterogeneous samples. Multimarker genetic analyses should benefit studies of complex aging-associated phenotypes.Item Open Access Puzzling role of genetic risk factors in human longevity: "risk alleles" as pro-longevity variants.(Biogerontology, 2016-02) Ukraintseva, Svetlana; Yashin, Anatoliy; Arbeev, Konstantin; Kulminski, Alexander; Akushevich, Igor; Wu, Deqing; Joshi, Gaurang; Land, Kenneth C; Stallard, EricComplex diseases are major contributors to human mortality in old age. Paradoxically, many genetic variants that have been associated with increased risks of such diseases are found in genomes of long-lived people, and do not seem to compromise longevity. Here we argue that trade-off-like and conditional effects of genes can play central role in this phenomenon and in determining longevity. Such effects may occur as result of: (i) antagonistic influence of gene on the development of different health disorders; (ii) change in the effect of gene on vulnerability to death with age (especially, from "bad" to "good"); (iii) gene-gene interaction; and (iv) gene-environment interaction, among other factors. A review of current knowledge provides many examples of genetic factors that may increase the risk of one disease but reduce chances of developing another serious health condition, or improve survival from it. Factors that may increase risk of a major disease but attenuate manifestation of physical senescence are also discussed. Overall, available evidence suggests that the influence of a genetic variant on longevity may be negative, neutral or positive, depending on a delicate balance of the detrimental and beneficial effects of such variant on multiple health and aging related traits. This balance may change with age, internal and external environments, and depend on genetic surrounding. We conclude that trade-off-like and conditional genetic effects are very common and may result in situations when a disease "risk allele" can also be a pro-longevity variant, depending on context. We emphasize importance of considering such effects in both aging research and disease prevention.Item Open Access The Global Epidemic of Childhood Obesity and Its Non-medical Costs(2015) Fu, QiangThis dissertation consists of three parts of empirical analyses investigating temporal patterns and consequences of (childhood) overweight and obesity, mainly in the United States and the People's Republic of China. Based on the China Health and Nutrition Survey, the first part conducts hierarchical age-period-cohort analyses of childhood overweight in China and finds a strong cohort effect driving the overweight epidemic. Results from the growth-curve models show that childhood overweight and underweight are related such that certain socio-economic groups with higher levels of childhood overweight also exhibit lower levels of childhood underweight. The second part situates the discussion on childhood obesity in a broader context. It compares temporal patterns of childhood overweight in China with these of adulthood overweight and finds that the salient cohort component is absent in rising adulthood overweight, which is dominated by strong period effects. A positive association between human development index and overweight/obesity prevalence across countries is also documented. Using multiple waves of survey data from the National Longitudinal Study of Adolescent Health, the third part analyzes the (latent) trajectory of childhood overweight/obesity in the United States. It finds that individuals with obesity growth trajectories are less likely to avoid mental depression, tend to have higher levels of neuroticism and lower levels of agreeableness/conscientiousness, and show less delinquent behaviors.
Item Open Access Trade-off in the effects of the apolipoprotein E polymorphism on the ages at onset of CVD and cancer influences human lifespan.(Aging Cell, 2011-06) Kulminski, Alexander M; Culminskaya, Irina; Ukraintseva, Svetlana V; Arbeev, Konstantin G; Arbeeva, Liubov; Wu, Deqing; Akushevich, Igor; Land, Kenneth C; Yashin, Anatoli IProgress in unraveling the genetic origins of healthy aging is tempered, in part, by a lack of replication of effects, which is often considered a signature of false-positive findings. We convincingly demonstrate that the lack of genetic effects on an aging-related trait can be because of trade-offs in the gene action. We focus on the well-studied apolipoprotein E (APOE) e2/3/4 polymorphism and on lifespan and ages at onset of cardiovascular diseases (CVD) and cancer, using data on 3924 participants of the Framingham Heart Study Offspring cohort. Kaplan-Meier estimates show that the e4 allele carriers live shorter lives than the non-e4 allele carriers (log rank = 0.016). The adverse effect was attributed to the poor survival of the e4 homozygotes, whereas the effect of the common e3/4 genotype was insignificant. The e3/4 genotype, however, was antagonistically associated with onsets of those diseases predisposing to an earlier onset of CVD and a later onset of cancer compared to the non-e4 allele genotypes. This trade-off explains the lack of a significant effect of the e3/4 genotype on survival; adjustment for it in the Cox regression model makes the detrimental effect of the e4 allele highly significant (P = 0.002). This trade-off is likely caused by the lipid-metabolism-related (for CVD) and nonrelated (for cancer) mechanisms. An evolutionary rationale suggests that genetic trade-offs should not be an exception in studies of aging-related traits. Deeper insights into biological mechanisms mediating gene action are critical for understanding the genetic regulation of a healthy lifespan and for personalizing medical care.Item Open Access Trajectories of Social Role Occupancy and Health: An Intra-Individual Analysis of Role Enhancement, Strain, and Context(2010) Sautter, Jessica MarieThis study examines whether trajectories of multiple social role occupancy, measured by level and dynamics of spouse, parent, and worker roles, are associated with mortality and concurrent trajectories of depressive symptoms and self-rated health. I frame hypotheses with role strain, role enhancement, role context, stress process, and life course theories to examine both within-person changes over age and between-person predictors of health status.
I use data from the Americans' Changing Lives Study, a nationally representative accelerated cohort panel study of U.S. adults interviewed in 1986, 1989, 1994, and 2001/2 with mortality tracking through 2006. I use latent class analysis to estimate disaggregated trajectories of role occupancy, role strain, role satisfaction, depressive symptoms, and self-rated health across the adult life course. I then use multinomial and logistic regression analyses to examine associations between role trajectories and health outcomes.
I find that (1) there is significant heterogeneity in trajectories of role occupancy and characteristics across the adult life course; (2) higher levels of social role occupancy are associated with better depressive symptom and mortality outcomes; (3) lower levels of role strain and higher levels of role satisfaction are associated with better depressive symptom outcomes, and (4); the association between role occupancy and health is robust to the inclusion of role characteristics. Thus, I find support for the role enhancement hypothesis in that higher levels of role occupancy are associated with better health outcomes irrespective of reward and strain associated with those roles.