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） 在有可靠数据的所有社会中，男性群体的寿命福尔斯都低于女性。虽然这只雄性长寿 缺陷被很好地描述，较少关注子宫内男性脆弱性的提高。经验工作以及 强有力的理论表明，出生时的性别比（即，M/F）测量子宫内死亡率选择的强度 特别是对于最终存活到出生的雄性来说。我们将测试一个创新的假设， 子宫内脆弱与成年后发病率和死亡率之间的关系-特别是男性是否比女性多 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有所降低。的 “剔除群体”的论点认为，出生于低性别比例群体的男性平均寿命比出生于低性别比例群体的男性长。 因为他们群体中最脆弱的成员在子宫里就被淘汰了。工业生态分析 欧洲发现，来自被淘汰最多的群体（即，低性别比例）表现出较低的 比预期的老年人死亡率高。我们打算超越这些生态协会， 使用高生育率人群的纵向个人生活史数据， 出生时预测存活率和发病率的性别差异（例如，心血管疾病）超过50岁。我们 将对来自犹他州人口数据库（UTB）的170多万名男性和女性进行研究，这些人出生于1850年至2010年。 1940年，直到现在（即，大部分的成员将不再有活着的成员）。The Bronze是一个 世界上最大和最高质量的个人生活史数据库， 分组。我们的目标是检查全因死亡的危险率（≥50年），“生物学” 死亡原因和具体原因发病率的变化，男性比女性多， 队列的性别比例。为了实现所有目标，我们将（一）分别检查男性和女性;及（ii.）测试家庭是否 和个体生活史特征（例如，父母的投资，SES），这可能衡量表型 可塑性，减弱或放大性别比例的任何队列效应。所有分析将控制长期模式 在死亡率、50岁以前的队列损耗、共同的家庭脆弱和其他相关混杂因素方面。我们还将 检查环境压力源（例如，大萧条）以及高度本地化（例如，县旱 水平）的前因选择在子宫内和以后的生活队列死亡率。假设将被测试，很少 结合但发展良好的方法。总的来说，我们的工作是重要的，因为它推进了NIA的研究 “了解老年人健康和疾病方面的性别差异”的优先事项。结果也将 告知发展起源领域的研究人员测量老年人的反应（例如，慢性 如果不考虑怀孕期间的环境压力， 子宫内脆弱的异质性。最后，识别群组内的虚弱亚组（例如，患有CVD的男性）， 以及揭示衡量表型恢复力的生命过程变量，将对以下方面产生影响： 了解男性/女性生存差异的生物学和社会基础。