Statistical Genetics Research Group, Institute of Medical Biometry, Heidelberg University, Heidelberg, Germany.
Centre for Global Health Research, Usher Institute, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, Scotland.
Hum Mol Genet. 2022 Mar 21;31(6):975-984. doi: 10.1093/hmg/ddab302.
The children of related parents show increased risk of early mortality. The Native American genome typically exhibits long stretches of homozygosity, and Latin Americans are highly heterogeneous regarding the individual burden of homozygosity, the proportion and the type of Native American ancestry. We analysed nationwide mortality and genome-wide genotype data from admixed Chileans to investigate the relationship between common causes of child mortality, homozygosity and Native American ancestry. Results from two-stage linear-Poisson regression revealed a strong association between the sum length of runs of homozygosity (SROH) above 1.5 Megabases (Mb) in each genome and mortality due to intracranial non-traumatic haemorrhage of foetus and newborn (5% increased risk of death per Mb in SROH, P = 1 × 10-3) and disorders related to short gestation and low birth weight (P = 3 × 10-4). The major indigenous populations in Chile are Aymara-Quechua in the north of the country and the Mapuche-Huilliche in the south. The individual proportion of Aymara-Quechua ancestry was associated with an increased risk of death due to anencephaly and similar malformations (P = 4 × 10-5), and the risk of death due to Edwards and Patau trisomy syndromes decreased 4% per 1% Aymara-Quechua ancestry proportion (P = 4 × 10-4) and 5% per 1% Mapuche-Huilliche ancestry proportion (P = 2 × 10-3). The present results suggest that short gestation, low birth weight and intracranial non-traumatic haemorrhage mediate the negative effect of inbreeding on human selection. Independent validation of the identified associations between common causes of child death, homozygosity and fine-scale ancestry proportions may inform paediatric medicine.
有亲缘关系父母的孩子有更高的早逝风险。美洲原住民的基因组通常表现出长的纯合区域，而拉丁美洲人在个体纯合负担、美洲原住民血统的比例和类型方面高度不均一。我们分析了混合的智利人的全因死亡率和全基因组基因型数据，以研究常见儿童死亡原因、纯合度和美洲原住民血统之间的关系。两阶段线性泊松回归的结果表明，每个基因组中超过 1.5Mb 的纯合区域（ROH）的总和长度与胎儿和新生儿的颅内非创伤性出血（每 Mb 的死亡风险增加 5%，P=1×10-3）和与早产和低出生体重相关的疾病之间存在很强的关联。智利的主要土著人群是北部的艾玛拉-克丘亚人和南部的马普切-惠尔切人。艾玛拉-克丘亚人的个体比例与无脑畸形和类似畸形（P=4×10-5）的死亡风险增加有关，而爱德华兹和帕套三体综合征的死亡风险则降低了 4%，每增加 1%的艾玛拉-克丘亚人血统比例（P=4×10-4）和每增加 1%的马普切-惠尔切人血统比例（P=2×10-3）。本研究结果表明，早产、低出生体重和颅内非创伤性出血介导了近亲繁殖对人类选择的负面影响。对常见儿童死亡原因、纯合度和精细血统比例之间已确定的关联进行独立验证，可能为儿科医学提供信息。
