Selection in utero and consequences for sex differences in adult mortality: a cohort approach

子宫内选择及其对成人死亡率性别差异的影响：队列方法

• 批准号: 10218425
• 负责人: Tim Allen Bruckner
• 金额: $ 24.45万
• 依托单位: UNIVERSITY OF CALIFORNIA-IRVINE
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-09-30 至 2023-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10218425
• 关键词: 5 year old; Accidents; Adult; Affect; Age; Alleles; Attention; Attenuated; Biological; Biological Aging; Birth; Cardiovascular Diseases; Cause of Death; Characteristics; Chronic Disease; Cohort Effect; Conceptions; Conflict (Psychology); County; Data; Databases; Death Rate; Demographer; Development; Disadvantaged; Disease; Droughts; Elderly; Europe; European; Exhibits; Family; Female; Fertility; Fetal Death; Genealogy; Heterogeneity; High Fertility Populations; Human; Individual; Industrialization; Investments; Lead; Life; Life Cycle Stages; Life Expectancy; Life Table Analyses; Link; Live Birth; Longevity; Malignant Neoplasms; Measures; Medical; Medical Records; Mental Depression; Methods; Morbidity - disease rate; Pattern; Phenotype; Population; Population Database; Pregnancy; Public Health; Quality of life; Research; Research Personnel; Research Priority; Risk; Sex Differences; Sex Ratio; Shapes; Societies; Subgroup; Terrorism; Testing; Utah; Variant; Woman; Work; cohort; comparison group; computerized; experience; falls; fetal loss; fitness; frailty; gender difference; hazard; health difference; in utero; innovation; life history; male; member; men; mortality; predictive modeling; resilience; response; social; stressor; theories

Project Summary (30 lines) Male cohort lifespan falls below female lifespan in all societies with reliable data. Although this male longevity deficit is well-described, less attention focuses on heightened male frailty in utero. Empirical work as well as strong theory indicates that the sex ratio at birth (i.e., M/F) gauges the strength of mortality selection in utero especially for males that ultimately survive to birth. We will test an innovative hypothesis which connects this frailty in utero to morbidity and mortality in older adulthood―specifically, whether males more than females born to the most selected birth cohorts show reduced morbidity and mortality rates at advanced ages. The “culled cohort” argument asserts that males born to low sex ratio cohorts live longer, on average, than expected because the frailest members of their group were culled in utero. Ecological analyses in industrial Europe find that males (but not females) born from the most culled cohorts (i.e., low sex ratio) exhibit lower than expected mortality rates at older ages. We intend to move beyond these ecological associations and test, using longitudinal, individual-level life history data from a high-fertility population whether the sex ratio at birth predicts sex differences in survival and morbidity (e.g., cardiovascular disease) beyond age 50. We will examine over 1.7 million males and females from the Utah Population Database (UPDB), born from 1850- 1940 and followed until the present (i.e., most cohorts will no longer have living members). The UPDB is one of the largest and highest quality individual-level life history databases in the world which may identify frail subgroups. Our aims will examine whether the hazard rate (≥50 years) of all-cause mortality, “biological” causes of mortality, and cause-specific morbidity varies for males more than females as a function of the cohort’s sex ratio. For all aims, we will (i.) examine males and females separately; and (ii.) test whether family and individual life-history characteristics (e.g., parental investments, SES), which may gauge phenotypic plasticity, attenuate or magnify any cohort effects of the sex ratio. All analyses will control for secular patterns in mortality, cohort attrition before age 50, shared family frailty, and other relevant confounders. We will also examine ambient stressors (e.g., Great Depression) as well as highly localized (e.g., drought at the county level) antecedents of selection in utero and later-life cohort mortality. Hypotheses will be tested with rarely combined but well-developed methods. Overall, our work is significant because it advances NIA’s research priority of “understanding sex and gender differences in health and disease at older ages.” Results will also inform the developmental origins field in that researchers measuring older-age responses (e.g., chronic disease) to ambient stressors during pregnancy may underestimate later-life adversity if they do not account for heterogeneity of frailty in utero. Lastly, identifying frail subgroups within a cohort (e.g., males with CVD), as well as uncovering life-course variables that gauge phenotypic resilience, would hold implications for understanding the biological and social basis of male/female differences in survival.

项目摘要(30行) 在所有有可靠数据的社会中，男性的寿命都低于女性的寿命。虽然这种男性的长寿 缺陷是很好的描述，较少的关注集中在子宫内男性的高度脆弱上。经验性工作以及 强有力的理论表明，出生性别比(即M/F)衡量的是子宫内死亡率选择的强度 尤其是那些最终存活到出生的雄性。我们将测试一个与此相关的创新假说 宫内脆弱对成年后发病率和死亡率的影响--特别是男性是否多于女性 出生于最精选的出生队列的人在高龄时的发病率和死亡率较低。这个 “剔除群体”的观点认为，平均而言，出生在低性别比群体的男性寿命要长于 这是意料之中的，因为他们团队中最虚弱的成员是在子宫里被扑杀的。工业中的生态分析 欧洲发现，男性(但不是女性)出生于被淘汰最多的群体(即性别比例较低)表现出较低的性别比例 高龄人群的死亡率高于预期。我们打算超越这些生态关联，并 检验，使用纵向、个人层面的生活史数据，来自高生育率人群的性别比 出生时预测50岁以后存活率和发病率(例如心血管疾病)的性别差异。我们 将检查犹他州人口数据库(UPDB)中的170多万名男性和女性，他们出生于1850年- 1940年，并一直沿用到现在(即大多数群体将不再有在世的成员)。UPDB就是其中之一 世界上最大和最高质量的个人生活史数据库，可以识别虚弱 子组。我们的目标将检验全因死亡率(≥50年)是否为“生物学的” 男性的死亡原因和特定原因的发病率比女性更不同，这是由于 队列的性别比。为了所有的目标，我们将(i.)分别检查男性和女性；及(Ii)测试族是否为 和个人生活史特征(例如，父母投资、社会保障)，这可以衡量表型 可塑性，减弱或放大性别比的任何队列效应。所有分析都将控制长期模式 死亡率、50岁之前的队列自然减员、共同的家庭脆弱以及其他相关的混杂因素。我们还将 检查环境应激源(例如，大萧条)以及高度局部性(例如，县内的干旱 水平)宫内选择和后世队列死亡率的先行因素。假设将在极少的情况下进行检验 结合起来但发展良好的方法。总体而言，我们的工作意义重大，因为它促进了NIA的研究 优先考虑“了解性别和性别差异在老年健康和疾病中的作用”。结果也将 告知发育起源领域，研究人员测量老年人的反应(例如，慢性 疾病)对怀孕期间的环境应激源的影响，如果不考虑这些因素，可能会低估晚年的逆境 对于宫内虚弱的异质性。最后，确定队列中的脆弱亚群(例如，患有心血管疾病的男性)， 以及揭示衡量表型韧性的生命过程变量，将对 了解男性/女性生存差异的生物学和社会基础。