Medical Research Council Integrative Epidemiology Unit, Population Health Sciences, University of Bristol, Bristol, United Kingdom.
Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, United Kingdom.
PLoS Genet. 2022 Jul 7;18(7):e1010247. doi: 10.1371/journal.pgen.1010247. eCollection 2022 Jul.
Estimating effects of parental and sibling genotypes (indirect genetic effects) can provide insight into how the family environment influences phenotypic variation. There is growing molecular genetic evidence for effects of parental phenotypes on their offspring (e.g. parental educational attainment), but the extent to which siblings affect each other is currently unclear. Here we used data from samples of unrelated individuals, without (singletons) and with biological full-siblings (non-singletons), to investigate and estimate sibling effects. Indirect genetic effects of siblings increase (or decrease) the covariance between genetic variation and a phenotype. It follows that differences in genetic association estimates between singletons and non-singletons could indicate indirect genetic effects of siblings if there is no heterogeneity in other sources of genetic association between singletons and non-singletons. We used UK Biobank data to estimate polygenic score (PGS) associations for height, BMI and educational attainment in self-reported singletons (N = 50,143) and non-singletons (N = 328,549). The educational attainment PGS association estimate was 12% larger (95% C.I. 3%, 21%) in the non-singleton sample than in the singleton sample, but the height and BMI PGS associations were consistent. Birth order data suggested that the difference in educational attainment PGS associations was driven by individuals with older siblings rather than firstborns. The relationship between number of siblings and educational attainment PGS associations was non-linear; PGS associations were 24% smaller in individuals with 6 or more siblings compared to the rest of the sample (95% C.I. 11%, 38%). We estimate that a 1 SD increase in sibling educational attainment PGS corresponds to a 0.025 year increase in the index individual's years in schooling (95% C.I. 0.013, 0.036). Our results suggest that older siblings may influence the educational attainment of younger siblings, adding to the growing evidence that effects of the environment on phenotypic variation partially reflect social effects of germline genetic variation in relatives.
估计父母和兄弟姐妹基因型（间接遗传效应）的影响可以深入了解家庭环境如何影响表型变异。越来越多的分子遗传学证据表明，父母表型对其后代有影响（例如，父母的受教育程度），但兄弟姐妹之间相互影响的程度目前尚不清楚。在这里，我们使用来自无生物学关系个体（单胎）和有生物学全同胞（多胎）样本的数据，来研究和估计兄弟姐妹效应。兄弟姐妹的间接遗传效应增加（或减少）了遗传变异与表型之间的协方差。因此，如果单胎和多胎之间在其他遗传关联来源上没有异质性，那么单胎和多胎之间遗传关联估计值的差异可能表明兄弟姐妹的间接遗传效应。我们使用英国生物库的数据，在自我报告的单胎（N=50143）和多胎（N=328549）中估计了身高、BMI 和教育程度的多基因评分（PGS）关联。在多胎样本中，教育程度 PGS 关联的估计值比单胎样本高 12%（95%CI3%，21%），而身高和 BMI 的 PGS 关联则一致。出生顺序数据表明，教育程度 PGS 关联的差异是由有年龄较大的兄弟姐妹的个体驱动的，而不是由头胎驱动的。兄弟姐妹数量与教育程度 PGS 关联之间的关系是非线性的；与样本其余部分相比，有 6 个或更多兄弟姐妹的个体的 PGS 关联低 24%（95%CI11%，38%）。我们估计，兄弟姐妹教育程度 PGS 每增加 1 个标准差，指数个体的受教育年限就会增加 0.025 年（95%CI0.013，0.036）。我们的结果表明，年龄较大的兄弟姐妹可能会影响年龄较小的兄弟姐妹的教育程度，这进一步证明了环境对表型变异的影响部分反映了亲缘关系中 germline 遗传变异的社会影响。
