PDF(Pubmed)
Abstract：
BACKGROUND: APOL1 variants G1 and G2 are common in populations with recent African ancestry. They are associated with protection from African sleeping sickness, however homozygosity or compound heterozygosity for these variants is associated with chronic kidney disease (CKD) and related conditions. What is not clear is the extent of associations with non-kidney-related disorders, and whether there are clusters of diseases associated with individual APOL1 genotypes.
METHODS: Using a cohort of 7462 UK Biobank participants with recent African ancestry, we conducted a phenome-wide association study investigating associations between individual APOL1 genotypes and conditions identified by the International Classification of Disease phenotypes.
RESULTS: We identified 27 potential associations between individual APOL1 genotypes and a diverse range of conditions. G1/G2 compound heterozygotes were specifically associated with 26 of these conditions (all deleteriously), with an over-representation of infectious diseases (including hospitalisation and death resulting from COVID-19). The analysis also exposed complexities in the relationship between APOL1 and CKD that are not evident when risk variants are grouped together: G1 homozygosity, G2 homozygosity, and G1/G2 compound heterozygosity were each shown to be associated with distinct CKD phenotypes. The multi-locus nature of the G1/G2 genotype means that its associations would go undetected in a standard genome-wide association study.
CONCLUSIONS: Our findings have implications for understanding health risks and better-targeted detection, intervention, and therapeutic strategies, particularly in populations where APOL1 G1 and G2 are common such as in sub-Saharan Africa and its diaspora.
BACKGROUND: This study was funded by the Wellcome Trust (209511/Z/17/Z) and H3Africa (H3A/18/004).
METHODS: Using a cohort of 7462 UK Biobank participants with recent African ancestry, we conducted a phenome-wide association study investigating associations between individual APOL1 genotypes and conditions identified by the International Classification of Disease phenotypes.
RESULTS: We identified 27 potential associations between individual APOL1 genotypes and a diverse range of conditions. G1/G2 compound heterozygotes were specifically associated with 26 of these conditions (all deleteriously), with an over-representation of infectious diseases (including hospitalisation and death resulting from COVID-19). The analysis also exposed complexities in the relationship between APOL1 and CKD that are not evident when risk variants are grouped together: G1 homozygosity, G2 homozygosity, and G1/G2 compound heterozygosity were each shown to be associated with distinct CKD phenotypes. The multi-locus nature of the G1/G2 genotype means that its associations would go undetected in a standard genome-wide association study.
CONCLUSIONS: Our findings have implications for understanding health risks and better-targeted detection, intervention, and therapeutic strategies, particularly in populations where APOL1 G1 and G2 are common such as in sub-Saharan Africa and its diaspora.
BACKGROUND: This study was funded by the Wellcome Trust (209511/Z/17/Z) and H3Africa (H3A/18/004).
摘要：
背景：APOL1变异体G1和G2在最近有非洲血统的人群中很常见。它们与防止非洲昏睡病有关，然而,这些变体的纯合性或复合杂合性与慢性肾脏病(CKD)及相关病症相关.尚不清楚与非肾脏相关疾病的关联程度，以及是否存在与个体APOL1基因型相关的疾病集群。
方法：使用7462名最近有非洲血统的UKBiobank参与者，我们进行了一项全表型关联研究,调查了APOL1基因型与国际疾病表型分类所确定的疾病之间的关联.
结果：我们确定了个体APOL1基因型与多种疾病之间的27种潜在关联。G1/G2复合杂合子与这些条件中的26种特异性相关（全部有害），传染病的发病率过高(包括住院和COVID-19导致的死亡)。分析还暴露了APOL1和CKD之间关系的复杂性，当风险变异被分组在一起时，这些复杂性并不明显：G1纯合性，G2纯合性，和G1/G2复合杂合性均显示与不同的CKD表型相关。G1/G2基因型的多基因座性质意味着其关联在标准的全基因组关联研究中不会被检测到。
结论：我们的发现对理解健康风险和更好的针对性检测具有重要意义。干预，和治疗策略，特别是在APOL1G1和G2常见的人群中，如撒哈拉以南非洲及其侨民。
背景：这项研究由WellcomeTrust（209511/Z/17/Z）和H3Africa（H3A/18/004）资助。
方法：使用7462名最近有非洲血统的UKBiobank参与者，我们进行了一项全表型关联研究,调查了APOL1基因型与国际疾病表型分类所确定的疾病之间的关联.
结果：我们确定了个体APOL1基因型与多种疾病之间的27种潜在关联。G1/G2复合杂合子与这些条件中的26种特异性相关（全部有害），传染病的发病率过高(包括住院和COVID-19导致的死亡)。分析还暴露了APOL1和CKD之间关系的复杂性，当风险变异被分组在一起时，这些复杂性并不明显：G1纯合性，G2纯合性，和G1/G2复合杂合性均显示与不同的CKD表型相关。G1/G2基因型的多基因座性质意味着其关联在标准的全基因组关联研究中不会被检测到。
结论：我们的发现对理解健康风险和更好的针对性检测具有重要意义。干预，和治疗策略，特别是在APOL1G1和G2常见的人群中，如撒哈拉以南非洲及其侨民。
背景：这项研究由WellcomeTrust（209511/Z/17/Z）和H3Africa（H3A/18/004）资助。
