Population Genetics Identifies Challenges in Analyzing Rare Variants

Geneticists have, for years, understood the nature of genome‐wide association studies using common genomic variants. Recently, however, focus has shifted to the analysis of rare variants. This presents potential problems for researchers, as rare variants do not always behave in the same way common variants do, sometimes rendering decades of solid intuition moot. In this paper, we present examples of the differences between common and rare variants. We show why one must be significantly more careful about the origin of rare variants, and how failing to do so can lead to highly inflated type I error. We then explain how to best avoid such concerns with careful understanding and study design. Additionally, we demonstrate that a seemingly low error rate in next‐generation sequencing can dramatically impact the false‐positive rate for rare variants. This is due to the fact that rare variants are, by definition, seen infrequently, making it hard to distinguish between errors and real variants. Compounding this problem is the fact that the proportion of errors is likely to get worse, not better, with increasing sample size. One cannot simply scale their way up in order to solve this problem. Understanding these potential pitfalls is a key step in successfully identifying true associations between rare variants and diseases.     

OCTA对青少年近视人群视网膜微血管密度的观察

目的：基于光学相干断层扫描血管成像（OCTA）技术探讨青少年儿童近视与视网膜表层微血管密度 及视网膜厚度的相关性。方法：横断面研究。共纳入2018年5─11月于四川大学华西医院眼科门 诊就诊的7～14岁青少年近视患者105例（193眼）。对所有受检者进行光学相干断层扫描（OCT）和 OCTA检查，量化分析黄斑中心凹视网膜厚度和各部位视网膜表层微血管密度。单因素方差分析比 较低、中、高度近视组各部位视网膜微血管密度及视网膜厚度的差异。采用Pearson相关系数探讨视 网膜厚度与各部位视网膜表层微血管密度的相关性。Spearman相关系数用于探讨等效球镜与中心凹、 旁中心凹视网膜表层微血管密度以及视网膜厚度的关系；分段多项式函数分析等效球镜度与外环及 直径6 mm完整视网膜表层微血管密度的关系。结果：旁中心凹、外环、直径6 mm完整区域视网膜 表层微血管密度在低、中、高度近视组间比较差异均具有统计学意义（F=11.651、14.499、14.232， 均P<0.001）。年龄与中心凹视网膜厚度之间有较弱正相关关系（r=0.187，P=0.011），与各部位微血管 密度均无相关性。等效球镜度与旁中心凹视网膜微血管密度有相关性（r=-0.301，P<0.001），与外环、 直径6 mm完整区域视网膜表层微血管密度呈曲线相关（r=-0.319，P<0.001；r=-0.307，P<0.001）。 但与中心凹视网膜表层微血管密度及视网膜厚度无显著相关性。此外，中心凹处视网膜厚度与微血 管密度呈正相关（r=0.691，P<0.001），与其余部位微血管密度无相关性。结论：青少年近视程度数 与旁中心凹、外环及直径6 mm完整区域视网膜表层微血管密度呈负相关；中心凹处视网膜厚度与年 龄、微血管密度呈正相关。     

Lower body mass index and higher height are correlated with increased varicocele risk

To evaluate the anthropometric indexes in subjects with varicocele compared to controls and the incidence of varicocele in different body mass index (BMI) groups for the purpose of exploring the association between varicocele and anthropometric indexes. A comprehensive literature search was conducted by using PubMed, MEDLINE, EMBASE databases and Cochrane Library up to February 2019. A systematic review and meta‐analysis was conducted by STATA, and Newcastle–Ottawa Scale was utilised for assessing risk of bias. Ultimately, 13 articles containing seven case–control studies and six cross‐sectional studies with 1,385,630 subjects were involved in our study. Pooled results demonstrated that varicocele patients had a lower BMI (WMD = ?0.77, 95% CI = ?1.03 to ?0.51) and a higher height than nonvaricocele participants, especially in grade 3 varicocele patients. Subgroup analyses showed that normal BMI individuals had a higher risk of varicocele than obese or overweight individuals and a lower risk than underweight individuals. In conclusion, this study indicates that varicocele patients have a lower BMI and a higher height than nonvaricocele participants. Moreover, men with excess bodyweight have a lower incidence of varicocele compared to normal weight or underweight people. That is to say, high BMI and adiposity protect against varicocele and high BMI is associated with a decreased risk of varicocele.