当前位置： SCI文献检索 > HUMAN MOLECULAR GENETICS期刊下所有文献 > Low-frequency germline variants across 6p22.2-6p21.33 are associated with non-obstructive azoospermia in Han Chinese men.

Low-frequency germline variants across 6p22.2-6p21.33 are associated with non-obstructive azoospermia in Han Chinese men.

Abstract：

:Genome-wide association studies (GWAS) have identified several common loci contributing to non-obstructive azoospermia (NOA). However, a substantial fraction of NOA heritability remains undefined, especially those low-frequency [defined here as having a minor allele frequency (MAF) between 0.5 and 5%] and rare (MAF below 0.5%) variants. Here, we performed a 3-stage exome-wide association study in Han Chinese men to evaluate the role of low-frequency or rare germline variants in NOA development. The discovery stage included 962 NOA cases and 1348 healthy male controls genotyped by exome chips and was followed by a 2-stage replication with an additional 2168 cases and 5248 controls. We identified three low-frequency variants located at 6p22.2 (rs2298090 in HIST1H1E encoding p.Lys152Arg: OR = 0.30, P = 2.40 × 10(-16)) and 6p21.33 (rs200847762 in FKBPL encoding p.Pro137Leu: OR = 0.11, P = 3.77 × 10(-16); rs11754464 in MSH5: OR = 1.78, P = 3.71 × 10(-7)) associated with NOA risk after Bonferroni correction. In summary, we report an instance of newly identified signals for NOA risk in genes previously undetected through GWAS on 6p22.2-6p21.33 in a Chinese population and highlight the role of low-frequency variants with a large effect in the process of spermatogenesis.

journal_name

Hum Mol Genet

journal_title

Human molecular genetics

authors

Ni B,Lin Y,Sun L,Zhu M,Li Z,Wang H,Yu J,Guo X,Zuo X,Dong J,Xia Y,Wen Y,Wu H,Li H,Zhu Y,Ping P,Chen X,Dai J,Jiang Y,Xu P,Du Q,Yao B,Weng N,Lu H,Wang Z,Zhu X,Yang X,Xiong C,Ma H,Jin G,Xu J,Wang

doi

10.1093/hmg/ddv257

subject

Has Abstract

pub_date

2015-10-01 00:00:00

pages

5628-36

issue

19

eissn

0964-6906

issn

1460-2083

pii

ddv257

journal_volume

24

pub_type

杂志文章

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