Linkage studies have successfully mapped loci underlying monogenic disorders, but mostly failed when applied to common diseases. Conversely, genome-wide association studies (GWASs) have identified replicable associations between thousands of SNPs and complex traits, yet capture less than half of the total heritability. In the present study we reconcile these two approaches by showing that linkage signals of height and body mass index (BMI) from 119,000 sibling pairs colocalize with GWAS-identified loci. Concordant with polygenicity, we observed the following: a genome-wide inflation of linkage test statistics; that GWAS results predict linkage signals; and that adjusting phenotypes for polygenic scores reduces linkage signals. Finally, we developed a method using recombination rate-stratified, identity-by-descent sharing between siblings to unbiasedly estimate heritability of height (0.76 ± 0.05) and BMI (0.55 ± 0.07). Our results imply that substantial heritability remains unaccounted for by GWAS-identified loci and this residual genetic variation is polygenic and enriched near these loci.

连锁研究已经成功地绘制了单基因疾病的位点，但在应用于常见疾病时大多失败。相反，全基因组关联研究 （GWAS） 已经确定了数千个 SNP 和复杂性状之间的可复制关联，但捕获的遗传性不到总遗传力的一半。在本研究中，我们通过表明来自 119,000 对兄弟姐妹的身高和体重指数 （BMI） 的连锁信号与 GWAS 鉴定的基因座共定位来调和这两种方法。与多基因性一致，我们观察到以下内容：连锁检验统计的全基因组膨胀;GWAS 结果预测连锁信号;并且调整多基因评分的表型会减少连锁信号。最后，我们开发了一种使用重组率分层、兄弟姐妹之间按血统共享身份的方法，以无偏估计身高 （0.76 ± 0.05） 和 BMI （0.55 ± 0.07） 的遗传性。我们的结果表明，GWAS 鉴定的基因座仍未解释实质性的遗传性，并且这种残余遗传变异是多基因的，并在这些基因座附近富集。