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） 在所有社会中，男性队列的寿命都低于女性寿命，并具有可靠的数据。虽然这个男性长寿 赤字被很好地描述了，注意力较少的重点是子宫内男性脆弱。经验工作和 强理论表明，出生时的性别比（即M/F）衡量了子宫内死亡率选择的强度 特别是对于最终生存到生存的男性而言。我们将测试一个创新的假设，该假设将其连接起来 特定于较早的成年期的子宫内的脆弱性和死亡率，男性是否比女性多 出生于最选择的出生队列显示出高年龄的发病率和死亡率降低。这 “被淘汰的队列”论点断言，低性别比例人群出生的男性平均寿命比 预计，因为他们小组中最糟糕的成员在子宫内被淘汰。工业生态分析 欧洲发现，雄性（但不是女性）是从最被淘汰的队列（即低性别比例）出生的较低的 年龄较大的年龄段的死亡率比预期的死亡率。我们打算超越这些生态关联和 测试，使用来自高植入率的纵向，个人级别的生活历史数据是否性别比例 在出生预测中，生存和发病率（例如心血管疾病）的性别差异超过50岁。 将研究来自1850年至1850年的犹他州人口数据库（UPDB）的170万男性和女性 1940年，直到现在（即，大多数队列将不再有活着的成员）。 UPDB是一个 世界上最大，最高质量的个人生活历史数据库是可以识别脆弱的 亚组。我们的目标将检查全因死亡率的危害率（≥50年）是否为“生物学” 与女性相比，男性的死亡率和特异性发病率的原因是 队列的性别比。对于所有目标，我们将（i。）分别检查男性和女性； （ii。）测试是否家庭 以及个人生活创造特征（例如，父母投资，SES），可以衡量表型 可塑性，减弱或放大性别比例的任何队列效应。所有分析将控制世俗模式 在死亡率中，50岁之前的人群流失，共同的家庭脆弱和其他相关的混杂因素。我们也会 检查环境压力源（例如，大萧条）以及高度局部（例如，在县的干旱 级别）在子宫和后期人群死亡率中选择的先例。假设将很少进行检验 结合但发达的方法。总体而言，我们的工作很重要，因为它可以推进NIA的研究 “了解老年健康和疾病中的性别和性别差异的优先级”。结果也将 告知发育起源领域，因为研究人员测量了老年反应（例如，慢性 疾病）到怀孕期间的环境压力源，如果不考虑的话，可能会低估以后的广告 对于子宫内脆弱的异质性。最后，识别队列中的脆弱亚组（例如，具有CVD的男性）， 除了发现衡量表型弹性的生活课程变量，还将对 了解男性/女性生存差异的生物学和社会基础。