Trampush Joey W, Lencz Todd, Knowles Emma, Davies Gail, Guha Saurav, Pe'er Itsik, Liewald David C, Starr John M, Djurovic Srdjan, Melle Ingrid, Sundet Kjetil, Christoforou Andrea, Reinvang Ivar, Mukherjee Semanti, DeRosse Pamela, Lundervold Astri, Steen Vidar M, John Majnu, Espeseth Thomas, Räikkönen Katri, Widen Elisabeth, Palotie Aarno, Eriksson Johan G, Giegling Ina, Konte Bettina, Ikeda Masashi, Roussos Panos, Giakoumaki Stella, Burdick Katherine E, Payton Antony, Ollier William, Horan Mike, Scult Matthew, Dickinson Dwight, Straub Richard E, Donohoe Gary, Morris Derek, Corvin Aiden, Gill Michael, Hariri Ahmad, Weinberger Daniel R, Pendleton Neil, Iwata Nakao, Darvasi Ariel, Bitsios Panos, Rujescu Dan, Lahti Jari, Le Hellard Stephanie, Keller Matthew C, Andreassen Ole A, Deary Ian J, Glahn David C, Malhotra Anil K
Division of Psychiatry Research, Zucker Hillside Hospital, Glen Oaks, New York.
Center for Psychiatric Neuroscience, Feinstein Institute for Medical Research, Manhasset, New York.
Am J Med Genet B Neuropsychiatr Genet. 2015 Jul;168B(5):363-73. doi: 10.1002/ajmg.b.32319. Epub 2015 May 7.
Cognitive deficits and reduced educational achievement are common in psychiatric illness; understanding the genetic basis of cognitive and educational deficits may be informative about the etiology of psychiatric disorders. A recent, large genome-wide association study (GWAS) reported a genome-wide significant locus for years of education, which subsequently demonstrated association to general cognitive ability ("g") in overlapping cohorts. The current study was designed to test whether GWAS hits for educational attainment are involved in general cognitive ability in an independent, large-scale collection of cohorts. Using cohorts in the Cognitive Genomics Consortium (COGENT; up to 20,495 healthy individuals), we examined the relationship between g and variants associated with educational attainment. We next conducted meta-analyses with 24,189 individuals with neurocognitive data from the educational attainment studies, and then with 53,188 largely independent individuals from a recent GWAS of cognition. A SNP (rs1906252) located at chromosome 6q16.1, previously associated with years of schooling, was significantly associated with g (P = 1.47 × 10(-4) ) in COGENT. The first joint analysis of 43,381 non-overlapping individuals for this a priori-designated locus was strongly significant (P = 4.94 × 10(-7) ), and the second joint analysis of 68,159 non-overlapping individuals was even more robust (P = 1.65 × 10(-9) ). These results provide independent replication, in a large-scale dataset, of a genetic locus associated with cognitive function and education. As sample sizes grow, cognitive GWAS will identify increasing numbers of associated loci, as has been accomplished in other polygenic quantitative traits, which may be relevant to psychiatric illness.
认知缺陷和学业成就降低在精神疾病中很常见;了解认知和学业缺陷的遗传基础可能有助于了解精神障碍的病因。最近一项大规模全基因组关联研究(GWAS)报告了一个全基因组范围内与受教育年限相关的显著位点,随后在重叠队列中证明该位点与一般认知能力(“g”)相关。本研究旨在测试在一个独立的大规模队列集合中,GWAS中与受教育程度相关的位点是否与一般认知能力有关。我们使用认知基因组学联盟(COGENT;多达20495名健康个体)的队列,研究了“g”与与受教育程度相关的变异之间的关系。接下来,我们对来自受教育程度研究的24189名有神经认知数据的个体进行了荟萃分析,然后对来自最近一项认知GWAS的53188名基本独立的个体进行了荟萃分析。位于6号染色体q16.1的一个单核苷酸多态性(SNP,rs1906252),先前与受教育年限相关,在COGENT中与“g”显著相关(P = 1.47×10^(-4))。对这个预先指定位点的43381名非重叠个体进行的首次联合分析具有高度显著性(P = 4.94×10^(-7)),对68159名非重叠个体进行的第二次联合分析更为有力(P = 1.65×10^(-9))。这些结果在一个大规模数据集中独立复制了一个与认知功能和教育相关的基因位点。随着样本量的增加,认知GWAS将识别出越来越多的相关位点,就像在其他多基因定量性状研究中所实现的那样,这些位点可能与精神疾病有关。