Objective:

Obsessive-compulsive disorder (OCD) is known to be substantially heritable; however, the contribution of genetic variation across the allele frequency spectrum to this heritability remains uncertain. The authors used two new homogeneous cohorts to estimate the heritability of OCD from inherited genetic variation and contrasted the results with those of previous studies.

Methods:

The sample consisted of 2,090 Swedish-born individuals diagnosed with OCD and 4,567 control subjects, all genotyped for common genetic variants, specifically >400,000 single-nucleotide polymorphisms (SNPs) with minor allele frequency (MAF) ≥0.01. Using genotypes of these SNPs to estimate distant familial relationships among individuals, the authors estimated the heritability of OCD, both overall and partitioned according to MAF bins.

Results:

Narrow-sense heritability of OCD was estimated at 29% (SE=4%). The estimate was robust, varying only modestly under different models. Contrary to an earlier study, however, SNPs with MAF between 0.01 and 0.05 accounted for 10% of heritability, and estimated heritability per MAF bin roughly followed expectations based on a simple model for SNP-based heritability.

Conclusions:

These results indicate that common inherited risk variation (MAF ≥0.01) accounts for most of the heritable variation in OCD. SNPs with low MAF contribute meaningfully to the heritability of OCD, and the results are consistent with expectation under the “infinitesimal model” (also referred to as the “polygenic model”), where risk is influenced by a large number of loci across the genome and across MAF bins.

中文翻译：

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强迫症的遗传结构：整个频谱等位基因对强迫症的易感性的贡献

客观的：

众所周知，强迫症 (OCD) 在很大程度上是可以遗传的；然而，跨等位基因频谱的遗传变异对这种遗传力的贡献仍然不确定。作者使用两个新的同质队列来估计 OCD 从遗传基因变异的遗传力，并将结果与​​之前的研究结果进行对比。

方法：

该样本由 2,090 名被诊断患有强迫症的瑞典出生个体和 4,567 名对照受试者组成，所有受试者均针对常见的遗传变异进行了基因分型，特别是 > 400,000 个单核苷酸多态性 (SNP)，次要等位基因频率 (MAF) ≥ 0.01。使用这些 SNP 的基因型来估计个体之间的远亲关系，作者估计了 OCD 的遗传力，包括总体遗传力和根据 MA​​F 区间划分的遗传力。

结果：

强迫症的狭义遗传率估计为 29% (SE=4%)。这个估计是稳健的，在不同的模型下变化不大。然而，与早期的研究相反，MAF 在 0.01 和 0.05 之间的 SNP 占遗传力的 10%，并且每个 MAF bin 的估计遗传力大致遵循基于 SNP 遗传力的简单模型的预期。

结论：

这些结果表明，常见的遗传风险变异 (MAF ≥ 0.01) 解释了强迫症的大部分遗传变异。具有低 MAF 的 SNP 对 OCD 的遗传力有重要贡献，结果与“无穷小模型”（也称为“多基因模型”）下的预期一致，其中风险受基因组中大量位点的影响和跨 MAF 箱。