Second, we should consider the following genes near rs848353 at 7q31.1: C7orf66, LOC154907, and PNPLA8-THAP5-DNAJB9. Although the function of the hypothetical protein-coding genes C7orf66 and LOC154907 remains to be determined, some biological interpretation of PNPLA8-THAP5-DNAJB9 is plausible. Patatin-like phospholipase domain containing 8 (PNPLA8), also known as phospholipase A2, catalyzes cleavage of fatty acids from phospholipids. The encoded product of PNPLA8 regulates membrane physical properties and the release of lipid second messengers and growth factors. THAP5 is a THAP domain containing 5 isoform 2, and DNAJB9 is a DnaJ (Hsp40) homolog, subfamily B, member 9. Numerous previous association findings at 7q31.1 for various phenotypes, such as death among heart failure patients (Morrison et al. 2010), ulcerative colitis (Asano et al. 2009; Barrett et al. 2009; McGovern et al. 2010; Silverberg et al. 2009), cognitive performance (Need et al. 2009), attention deficit hyperactivity disorder (Anney et al. 2008; Lasky-Su et al. 2008), and serum metabolites (Gieger et al. 2008), may imply an important role for this locus in the etiology of these complex disorder/phenotypes.
