Runs of homozygosity implicate autozygosity as a schizophrenia risk factor.
Runs of homozygosity implicate autozygosity as a schizophrenia risk factor.
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DOI：
10.1371/journal.pgen.1002656
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发表时间：
2012
期刊：
影响因子：
4.5
通讯作者：
Schizophrenia Psychiatric Genome-Wide Association Study Consortium
中科院分区：
文献类型：
--
作者：
Keller MC;Simonson MA;Ripke S;Neale BM;Gejman PV;Howrigan DP;Lee SH;Lencz T;Levinson DF;Sullivan PF;Schizophrenia Psychiatric Genome-Wide Association Study Consortium
当来自共同祖先的两个相同的染色体片段从每个亲本遗传时，发生自体接合性。这种情况在近亲（近亲繁殖）的后代中发生率很高，但在远亲的后代中也发生率较低。在这里，我们使用全基因组SNP数据中的纯合性来估计9，388例精神分裂症患者和12，456例对照组中存在于纯合束中的常染色体比例。我们估计，全基因组同源性每增加1%，精神分裂症的几率就增加1.17%。这种关联不是由于一个或几个区域，而是由分布在整个基因组中的许多纯合子片段引起的，并且与精神分裂症病因学中多个隐性或部分隐性等位基因的作用一致。这种对隐性的偏向表明，增加精神分裂症风险的等位基因在进化过程中被选择了。近亲繁殖发生在遗传亲属有后代的时候。因为所有的人都是彼此相关的，即使是非常遥远的，所有的人都是不同程度的近亲繁殖。从遗传学的角度来看，众所周知，近亲繁殖会增加孩子患罕见隐性遗传病的风险，但人们也越来越有兴趣了解近亲繁殖是否是精神分裂症等更常见、更复杂疾病的风险因素。在这项研究中，我们使用单核苷酸多态性数据来量化9，388例精神分裂症病例和12，456例对照的近亲繁殖程度，并测试了基因组显示近亲繁殖证据较高的人患精神分裂症的风险较高的假设。我们估计，近亲繁殖每增加1%，精神分裂症的几率就增加17%。这一发现与多重隐性或部分隐性等位基因在精神分裂症病因学中的作用一致，并且它表明增加精神分裂症风险的遗传变异在进化过程中被选择。
Autozygosity occurs when two chromosomal segments that are identical from a common ancestor are inherited from each parent. This occurs at high rates in the offspring of mates who are closely related (inbreeding), but also occurs at lower levels among the offspring of distantly related mates. Here, we use runs of homozygosity in genome-wide SNP data to estimate the proportion of the autosome that exists in autozygous tracts in 9,388 cases with schizophrenia and 12,456 controls. We estimate that the odds of schizophrenia increase by ∼17% for every 1% increase in genome-wide autozygosity. This association is not due to one or a few regions, but results from many autozygous segments spread throughout the genome, and is consistent with a role for multiple recessive or partially recessive alleles in the etiology of schizophrenia. Such a bias towards recessivity suggests that alleles that increase the risk of schizophrenia have been selected against over evolutionary time. Inbreeding occurs when genetic relatives have offspring. Because all humans are related to one another, even if very distantly, all people are inbred to various degrees. From a genetic standpoint, it is well known that inbreeding increases the risk that a child will have a rare recessive genetic disease, but there is also increasing interest in understanding whether inbreeding is a risk factor for more common, complex disorders such as schizophrenia. In this investigation, we used single-nucleotide polymorphism data to quantify the degree to which 9,388 schizophrenia cases and 12,456 controls were inbred, and we tested the hypothesis that people whose genome shows higher evidence of being inbred are at higher risk of having schizophrenia. We estimate that the odds of schizophrenia increase by ∼17% for every 1% increase in inbreeding. This finding is consistent with a role for multiple recessive or partially recessive alleles in the etiology of schizophrenia, and it suggests that genetic variants that increase the risk of schizophrenia have been selected against over evolutionary time.
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